Details of the Researcher

PHOTO

Yoshihiro Kushida
Section
Graduate School of Medicine
Job title
Assistant Professor
Degree

  • 博士（理学）（新潟大学）

  • 修士（理学）（新潟大学）

e-Rad No.
10707003

Research History 4

  • 2020/10 - Present
    Dokkyo Medical University　Research Center for Advanced Medical Science

  • 2016/04 - Present
    Tohoku University　Graduate School of Medicine

  • 2013/04 - 2016/03
    Tohoku University　Graduate School of Medicine

  • 2012/04 - 2013/03
    Tohoku University　Graduate School of Medicine

Education 2

  • Niigata University　Graduate School of Science and Technology

    2009/04 - 2012/03

  • Niigata University　Graduate School of Science and Technology

    2007/04 - 2009/03

Committee Memberships 1

  • 日本顕微鏡学会　評議員

    2021/04 - Present

Professional Memberships 4

  • 量子生命科学会

  • THE JAPANESE SOCIETY OF MICROSCOPY

  • THE JAPANESE ASSOCIATION OF ANATOMISTS

  • THE JAPANESE SOCIETY FOR REGENERATIVE MEDICINE

Research Interests 3

  • Muse細胞

  • 再生医学

  • 幹細胞

Research Areas 1

  • Life sciences / Anatomy /

Awards 3

  1. 優秀演題賞

    2024/03　第23回日本再生医療学会総会

  2. President Award

    2015/11　The 42th Annual Meeting of the Japan Society for Organ Preservation and Biology

  3. 特に優れた業績による大学院第一種奨学生返還免除

    2012/03　独立行政法人 日本学生支援機構　全額免除

Papers 44

  1. Nose-to-brain delivery of human muse cells enhances structural and functional recovery in the murine ischemic stroke model. International-journal

    Shusuke Yamamoto, Keitaro Shiraishi, Yoshihiro Kushida, Yo Oguma, Shohei Wakao, Mari Dezawa, Satoshi Kuroda

    Scientific reports　15　(1)　16243-16243　2025/05/09

    DOI： 10.1038/s41598-025-96451-3 　

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    Muse cells are endogenous, non-tumorigenic, pluripotent-like stem cells already applied to clinical trials based on intravenous injection. They can selectively home to the post-infarct area, replenish apoptotic neural cells by phagocytosis-induced differentiation, and enhance functional recovery. The effect of nose-to-brain delivery of Muse cells on cerebral infarct was examined. Permanent middle cerebral artery occlusion model BALB/c mice received intranasal administration of either human Muse cells (6.0 × 104 cells), high-dose human-mesenchymal stem cells (MSCs) (1.6 × 106 cells), low-dose human-MSCs (6.0 × 104 cells), or vehicle at 7 days after onset. An accelerated rotarod test and a histological assessment were done. The vehicle- or low-dose MSC groups showed no significant improvement in the rotarod test. In the high-dose MSC group, motor function was transiently recovered, but the therapeutic effect disappeared thereafter. The Muse group continuously improved motor function, with statistical significance to the other groups. The engraftment of administered cells in the peri-infarct area was the highest in the Muse group, while few cells were detected in other groups. 63.6 ± 8.5% and 26.2 ± 3.0% of Muse cells were positive for NeuN and GSTpi, respectively. Intranasal administration of Muse cells might be a viable approach to improving functional recovery with less invasiveness after ischemic stroke.

  2. Accumulation of endogenous Muse cells in the myocardium and its pathophysiological role in patients with fulminant myocarditis. International-journal Peer-reviewed

    Shigeru Toyoda, Masashi Sakuma, Kazuyuki Ishida, Yoshihiro Kushida, Ryoichi Soma, Hidehito Takayama, Kazumi Akimoto, Mari Dezawa, Teruo Inoue

    Clinical and translational science　17　(11)　e70067　2024/11

    DOI： 10.1111/cts.70067 　

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    Multi-lineage differentiating stress-enduring (Muse) cells, identified as pluripotent surface marker SSEA-3(+) cells, are stress tolerant endogenous pluripotent-like stem cells, and are involved in tissue repair. However, the significance of Muse cells in acute myocarditis has not been evaluated. In the present study, we counted Muse cells/area in biopsied myocardial tissue samples from 17 patients with fulminant myocarditis, and 6 with non-inflammatory myocardial disease as controls. Compared with controls, patients with fulminant myocarditis had significantly more Muse cells (p = 0.00042). Patients with mechanical circulatory support (p = 0.006) and myocardial degeneration (p = 0.023) had significantly more Muse cells than those without them. The Muse cell number was correlated with acute phase CK-MB level (ρ = 0.547, p = 0.029), indicating the severity of myocardial injury, and was also correlated with acute/recovery phase ratio of CK-MB (ρ = 0.585, p = 0.023) and cardiac troponin I (ρ = 0.498, p = 0.047) levels, indicating resilience of myocardial injury. In fulminant myocarditis, the Muse cell number was associated with the severity of clinical features in the acute phase, and also with the recovery from myocardial damage in the chronic phase. Endogenous Muse cells might be mobilized and accumulate to the myocardial tissues in fulminant myocarditis, and might participate in the repair of injured myocardium.

  3. Structural reconstruction of mouse acute aortic dissection by intravenously administered human Muse cells without immunosuppression. International-journal Peer-reviewed

    Makoto Takahashi, Yoshihiro Kushida, Yasumasa Kuroda, Shohei Wakao, Yasuhiro Horibata, Hiroyuki Sugimoto, Mari Dezawa, Yoshikatsu Saiki

    Communications medicine　4　(1)　174-174　2024/09/09

    DOI： 10.1038/s43856-024-00597-6 　

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    BACKGROUND: Stanford type B-acute aortic dissection (type B-AAD) is often life-threatening without invasive surgery. Multilineage-differentiating stress enduring cell (Muse cells), which comprise several percent of mesenchymal stem cells (MSCs), are endogenous pluripotent-like stem cells that selectively home to damaged tissue and replace damaged/apoptotic cells by in-vivo differentiation. METHODS: Mortality, aortic diameter expansion, cell localization, cell differentiation, and inflammation of the dissected aorta were evaluated in type B-AAD model mice intravenously injected with human-Muse cells, -elastin-knockdown (KD)-Muse cells, -human leukocyte antigen-G (HLA-G)-KD-Muse cells, or MSCs, all without immunosuppressant. RESULTS: Here, we show the Muse (50,000 cells) group has a lower incidence of aortic rupture and mortality of AAD compared with the MSC-50K (50,000 human-MSCs) and vehicle groups. Spectrum computed tomography in-vivo dynamics and 3-dimensional histologic analyses demonstrate that Muse cells more effectively home to the AAD tissue and survive for 8 weeks in the Muse group than in the MSC-750K (750,000 human-MSCs containing 50,000 Muse cells) group. Homing of Muse cells is impeded in the HLA-G-KD-Muse (50,000 cells) group. Differentiation of homed Muse cells into CD31(+) and alpha-smooth muscle actin (+) cells, production and reorganization of elastic fibers in the AAD tissue, and suppression of diameter expansion are greater in the Muse group than in the MSC-750K and elastin-KD-Muse (50,000 cells) groups. CONCLUSIONS: Intravenously administered Muse cells reconstruct the dissected aorta and improve mortality and diameter enlargement rates. Moreover, small doses of purified Muse cells are more effective than large doses of MSCs. HLA-G is suggested to contribute to the successful survival and homing of Muse cells.

  4. Human post-implantation blastocyst-like characteristics of Muse cells isolated from human umbilical cord. International-journal Peer-reviewed

    Yoshihiro Kushida, Yo Oguma, Kana Abe, Taichi Deguchi, Federico Girolamo Barbera, Noriyuki Nishimura, Kazumichi Fujioka, Sota Iwatani, Mari Dezawa

    Cellular and molecular life sciences : CMLS　81　(1)　297-297　2024/07/11

    DOI： 10.1007/s00018-024-05339-4 　

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    Muse cells, identified as cells positive for the pluripotent surface marker SSEA-3, are pluripotent-like endogenous stem cells located in the bone marrow (BM), peripheral blood, and organ connective tissues. The detailed characteristics of SSEA-3(+) cells in extraembryonic tissue, however, are unknown. Here, we demonstrated that similar to human-adult tissue-Muse cells collected from the BM, adipose tissue, and dermis as SSEA-3(+), human-umbilical cord (UC)-SSEA-3(+) cells express pluripotency markers, differentiate into triploblastic-lineage cells at a single cell level, migrate to damaged tissue, and exhibit low telomerase activity and non-tumorigenicity. Notably, ~ 20% of human-UC-SSEA-3(+) cells were negative for X-inactive specific transcript (XIST), a naïve pluripotent stem cell characteristic, whereas all human adult tissue-Muse cells are XIST-positive. Single-cell RNA sequencing revealed that the gene expression profile of human-UC-SSEA-3(+) cells was more similar to that of human post-implantation blastocysts than human-adult tissue-Muse cells. The DNA methylation level showed the same trend, and notably, the methylation levels in genes particularly related to differentiation were lower in human-UC-SSEA-3(+) cells than in human-adult tissue-Muse cells. Furthermore, human-UC-SSEA-3(+) cells newly express markers specific to extraembryonic-, germline-, and hematopoietic-lineages after differentiation induction in vitro whereas human-adult tissue-Muse cells respond only partially to the induction. Among various stem/progenitor cells in living bodies, those that exhibit properties similar to post-implantation blastocysts in a naïve state have not yet been found in humans. Easily accessible human-UC-SSEA-3(+) cells may be a valuable tool for studying early-stage human development and human reproductive medicine.

  5. New rat model of spinal cord infarction with long-lasting functional disabilities generated by intraspinal injection of endothelin-1 Peer-reviewed

    Masayuki Otani, Yoshihiro Kushida, Yasumasa Kuroda, Shohei Wakao, Yo Oguma, Keisuke Sasaki, Shintaro Katahira, Ryohei Terai, Rie Ryoke, Hiroi Nonaka, Ryuta Kawashima, Yoshikatsu Saiki, Mari Dezawa

    Stroke and Vascular Neurology　svn-2023　2024/06/21

    Publisher: BMJ

    DOI： 10.1136/svn-2023-002962 　

    ISSN： 2059-8688

    eISSN： 2059-8696

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    Background The current method for generating an animal model of spinal cord (SC) infarction is highly invasive and permits only short-term observation, typically limited to 28 days. Objective We aimed to establish a rat model characterised by long-term survival and enduring SC dysfunction by inducing selective ischaemic SC damage. Methods In 8-week-old male Wistar rats, a convection-enhanced delivery technique was applied to selectively deliver endothelin-1 (ET-1) to the anterior horn of the SC at the Th13 level, leading to SC infarction. The Basso, Beattie and Bresnahan (BBB) locomotor score was assessed for 56 days. The SC was examined by a laser tissue blood flowmeter, MRI, immunohistochemistry, triphenyl tetrazolium chloride (TTC) staining, Western blots and TUNEL staining. Results The puncture method was used to bilaterally inject 0.7 µL ET-1 (2.5 mg/mL) from the lateral SC into the anterior horns (40° angle, 1.5 mm depth) near the posterior root origin. Animals survived until day 56 and the BBB score was stably maintained (5.5±1.0 at day 14 and 6.2±1.0 at day 56). Rats with BBB scores ≤1 on day 1 showed stable scores of 5–6 after day 14 until day 56 while rats with BBB scores >1 on day 1 exhibited only minor dysfunction with BBB scores >12 after day 14. TTC staining, immunostaining and TUNEL staining revealed selective ischaemia and neuronal cell death in the anterior horn. T2-weighted MR images showed increasing signal intensity at the SC infarction site over time. Western blots revealed apoptosis and subsequent inflammation in SC tissue after ET-1 administration. Conclusions Selective delivery of ET-1 into the SC allows for more precise localisation of the infarcted area at the targeted site and generates a rat SC infarction model with stable neurological dysfunction lasting 56 days.

  6. Human Muse cells isolated from preterm- and term-umbilical cord delivered therapeutic effects in rat bleomycin-induced lung injury model without immunosuppressant. International-journal Peer-reviewed

    Kaung Htet Nay Win, Yoshihiro Kushida, Keiji Yamana, Sota Iwatani, Makiko Yoshida, Nanako Nino, Cho Yee Mon, Hiroyuki Ohsaki, Shingo Kamoshida, Kazumichi Fujioka, Mari Dezawa, Noriyuki Nishimura

    Stem cell research & therapy　15　(1)　147-147　2024/05/22

    DOI： 10.1186/s13287-024-03763-8 　

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    BACKGROUND: Bleomycin (BLM)-induced lung injury is characterized by mixed histopathologic changes with inflammation and fibrosis, such as observed in human patients with bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. Although no curative therapies for these lung diseases exist, stem cell therapy has emerged as a potential therapeutic option. Multilineage-differentiating stress-enduring (Muse) cells are endogenous pluripotent- and macrophage-like stem cells distributed in various adult and fetal tissues as stage-specific embryonic antigen-3-positive cells. They selectively home to damaged tissue by sensing sphingosine-1-phosphate and replace the damaged/apoptotic cells by in vivo differentiation. Clinical trials for some human diseases suggest the safety and therapeutic efficacy of intravenously injected human leukocyte antigen-mismatched allogenic Muse cells from adult bone marrow (BM) without immunosuppressant. Here, we evaluated the therapeutic effects of human Muse cells from preterm and term umbilical cord (UC), and adult BM in a rat BLM-induced lung injury model. METHODS: Rats were endotracheally administered BLM to induce lung injury on day 0. On day 3, human preterm UC-Muse, term UC-Muse, or adult BM-Muse cells were administered intravenously without immunosuppressants, and rats were subjected to histopathologic analysis on day 21. Body weight, serum surfactant protein D (SP-D) levels, and oxygen saturation (SpO2) were monitored. Histopathologic lung injury scoring by the Ashcroft and modified American Thoracic Society document scales, quantitative characterization of engrafted Muse cells, RNA sequencing analysis, and in vitro migration assay of infused Muse cells were performed. RESULTS: Rats administered preterm- and term-UC-Muse cells exhibited a significantly better recovery based on weight loss, serum SP-D levels, SpO2, and histopathologic lung injury scores, and a significantly higher rate of both Muse cell homing to the lung and alveolar marker expression (podoplanin and prosurfactant protein-C) than rats administered BM-Muse cells. Rats receiving preterm-UC-Muse cells showed statistically superior results to those receiving term-UC-Muse cells in many of the measures. These findings are thought to be due to higher expression of genes related to cell migration, lung differentiation, and cell adhesion. CONCLUSION: Preterm UC-Muse cells deliver more efficient therapeutic effects than term UC- and BM-Muse cells for treating BLM-induced lung injury in a rat model.

  7. Intravenously engrafted human multilineage-differentiating stress-enduring (Muse) cells rescue erectile function after rat cavernous nerve injury. International-journal Peer-reviewed

    Juntaro Koyama, Shinichi Yamashita, Yuya Kato, Kunihisa Nezu, Takuro Goto, Shinji Fujii, Yu Suzuki, Atsushi Nakayashiki, Yoshihide Kawasaki, Naoki Kawamorita, Hitomi Okita, Takako Ito, Yoshihiro Kushida, Masafumi Goto, Mari Dezawa, Teiji Tominaga, Kuniyasu Niizuma, Akihiro Ito

    BJU international　2023/11/20

    DOI： 10.1111/bju.16232 　

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    OBJECTIVE: To evaluate the effect of intravenous administration of human multilineage-differentiating stress-enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomised into three groups after CN crush injury. Either human-Muse cells, non-Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non-Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C-X-C motif chemokine ligand (Cxcl12) and glial cell line-derived neurotrophic factor (Gdnf) in the MPG were examined by real-time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one-way analysis of variance followed by the Tukey test for parametric data and Kruskal-Wallis test followed by the Dunn-Bonferroni test for non-parametric data. RESULTS: The mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non-Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non-Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non-Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion. CONCLUSION: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.

  8. Single-cell RNA sequencing reveals different signatures of mesenchymal stromal cell pluripotent-like and multipotent populations. International-journal Peer-reviewed

    Yo Oguma, Yasumasa Kuroda, Shohei Wakao, Yoshihiro Kushida, Mari Dezawa

    iScience　25　(11)　105395-105395　2022/11/18

    DOI： 10.1016/j.isci.2022.105395 　

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    Somatic stem cells are advantageous research targets for understanding the properties required to maintain stemness. Human bone marrow-mesenchymal stromal cells (BM-MSCs) were separated into pluripotent-like SSEA-3(+) Muse cells (Muse-MSCs) and multipotent SSEA-3(-) MSCs (MSCs) and were subjected to single-cell RNA sequencing analysis. Compared with MSCs, Muse-MSCs exhibited higher expression levels of the p53 repressor MDM2; signal acceptance-related genes EGF, VEGF, PDGF, WNT, TGFB, INHB, and CSF; ribosomal protein; and glycolysis and oxidative phosphorylation. Conversely, MSCs had higher expression levels of FGF and ANGPT; Rho family and caveola-related genes; amino acid and cofactor metabolism; MHC class I/II, and lysosomal enzyme genes than Muse-MSCs. Unsupervised clustering further divided Muse-MSCs into two clusters stratified by the expression of cell cycle-related genes, and MSCs into three clusters stratified by the expression of cell cycle-, cytoskeleton-, and extracellular matrix-related genes. This study evaluating the differentiation ability of BM-MSC subpopulations provides intriguing insights for understanding stemness.

  9. Naïve pluripotent-like characteristics of non-tumorigenic Muse cells isolated from human amniotic membrane. International-journal Peer-reviewed

    Eiji Ogawa, Yo Oguma, Yoshihiro Kushida, Shohei Wakao, Kana Okawa, Mari Dezawa

    Scientific reports　12　(1)　17222-17222　2022/10/14

    DOI： 10.1038/s41598-022-22282-1 　

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    Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic pluripotent-like stem cells that exhibit triploblastic differentiation and self-renewability at the single-cell level, and are collectable as pluripotent surface marker SSEA-3(+) from the bone marrow (BM), peripheral blood, and organ connective tissues. SSEA-3(+) cells from human amniotic membrane mesenchymal stem cells (hAMSCs) were compared with hBM-Muse cells. Similar to hBM-Muse cells, hAMSC-SSEA-3(+) cells expressed pluripotency genes (OCT3/4, NANOG, and SOX2), differentiated into triploblastic cells from a single cell, self-renewed, and exhibited non-tumorigenicity. Notably, however, they exhibited unique characteristics not seen in hBM-Muse cells, including higher expression of genes related to germline- and extraembryonic cell-lineages compared with those in hBM-Muse cells in single-cell RNA-sequencing; and enhanced expression of markers relevant to germline- (PRDM14, TFAP2C, and NANOS3) and extraembryonic cell- (CDX2, GCM1, and ID2) lineages when induced by cytokine subsets, suggesting a broader differentiation potential similar to naïve pluripotent stem cells. t-SNE dimensionality reduction and Gene ontology analysis visualized hAMSC-SSEA-3(+) cells comprised a large undifferentiated subpopulation between epithelial- and mesenchymal-cell states and a small mesenchymal subpopulation expressing genes relevant to the placental formation. The AM is easily accessible by noninvasive approaches. These unique cells are a potentially interesting target naïve pluripotent stem cell-like resource without tumorigenicity.

  10. Phagocytosing differentiated cell-fragments is a novel mechanism for controlling somatic stem cell differentiation within a short time frame. International-journal Peer-reviewed

    Shohei Wakao, Yo Oguma, Yoshihiro Kushida, Yasumasa Kuroda, Kazuki Tatsumi, Mari Dezawa

    Cellular and molecular life sciences : CMLS　79　(11)　542-542　2022/10/06

    DOI： 10.1007/s00018-022-04555-0 　

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    Stem cells undergo cytokine-driven differentiation, but this process often takes longer than several weeks to complete. A novel mechanism for somatic stem cell differentiation via phagocytosing 'model cells' (apoptotic differentiated cells) was found to require only a short time frame. Pluripotent-like Muse cells, multipotent mesenchymal stem cells (MSCs), and neural stem cells (NSCs) phagocytosed apoptotic differentiated cells via different phagocytic receptor subsets than macrophages. The phagocytosed-differentiated cell-derived contents (e.g., transcription factors) were quickly released into the cytoplasm, translocated into the nucleus, and bound to promoter regions of the stem cell genomes. Within 24 ~ 36 h, the cells expressed lineage-specific markers corresponding to the phagocytosed-differentiated cells, both in vitro and in vivo. At 1 week, the gene expression profiles were similar to those of the authentic differentiated cells and expressed functional markers. Differentiation was limited to the inherent potential of each cell line: triploblastic-, adipogenic-/chondrogenic-, and neural-lineages in Muse cells, MSCs, and NSCs, respectively. Disruption of phagocytosis, either by phagocytic receptor inhibition via small interfering RNA or annexin V treatment, impeded differentiation in vitro and in vivo. Together, our findings uncovered a simple mechanism by which differentiation-directing factors are directly transferred to somatic stem cells by phagocytosing apoptotic differentiated cells to trigger their rapid differentiation into the target cell lineage.

  11. Inhibition of Gap Junctional Intercellular Communication Upregulates Pluripotency Gene Expression in Endogenous Pluripotent Muse Cells Peer-reviewed

    Khaled Hatabi, Yukari Hirohara, Yoshihiro Kushida, Yasumasa Kuroda, Shohei Wakao, James Trosko, Mari Dezawa

    Cells　11　(17)　2701-2701　2022/08/30

    Publisher: MDPI AG

    DOI： 10.3390/cells11172701 　

    eISSN： 2073-4409

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    Gap junctions (GJ) are suggested to support stem cell differentiation. The Muse cells that are applied in clinical trials are non-tumorigenic pluripotent-like endogenous stem cells, can be collected as stage-specific embryonic antigen 3 (SSEA-3+) positive cells from multiple tissues, and show triploblastic differentiation and self-renewability at a single cell level. They were reported to up-regulate pluripotency gene expression in suspension. We examined how GJ inhibition affected pluripotency gene expression in adherent cultured-Muse cells. Muse cells, mainly expressing gap junction alpha-1 protein (GJA1), reduced GJ intercellular communication from ~85% to 5–8% after 24 h incubation with 120 μM 18α-glycyrrhetinic acid, 400 nM 12-O-tetradecanoylphorbol-13-acetate, and 90 μM dichlorodiphenyltrichloroethane, as confirmed by a dye-transfer assay. Following inhibition, NANOG, OCT3/4, and SOX2 were up-regulated 2–4.5 times more; other pluripotency-related genes, such as KLF4, CBX7, and SPRY2 were elevated; lineage-specific differentiation-related genes were down-regulated in quantitative-PCR and RNA-sequencing. Connexin43-siRNA introduction also confirmed the up-regulation of NANOG, OCT3/4, and SOX2. YAP, a co-transcriptional factor in the Hippo signaling pathway that regulates pluripotency gene expression, co-localized with GJA1 (also known as Cx43) in the cell membrane and was translocated to the nucleus after GJ inhibition. Adherent culture is usually more suitable for the stable expansion of cells than is a suspension culture. GJ inhibition is suggested to be a simple method to up-regulate pluripotency in an adherent culture that involves a Cx43-YAP axis in pluripotent stem cells, such as Muse cells.

  12. Intravenous administration of human Muse cells recovers blood flow in a mouse model of hindlimb ischemia. International-journal Peer-reviewed

    Yusuke Hori, Tomoya Kitani, Kenji Yanishi, Takaomi Suga, Masaya Kogure, Tetsuro Kusaba, Yoshihiro Kushida, Mari Dezawa, Satoaki Matoba

    Frontiers in cardiovascular medicine　9　981088-981088　2022

    DOI： 10.3389/fcvm.2022.981088 　

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    Cell-based therapies hold great promise for the treatment of peripheral arterial disease (PAD), especially in patients presenting with severe limb ischemia, although the optimal strategy remains to be explored. In this study, we evaluated the therapeutic effect of intravenous administration of human Muse cells, a unique subpopulation of mesenchymal stem cells (MSC), using a mouse model of hindlimb ischemia (HLI) without an immunosuppressant. Compared with the phosphate buffered saline (PBS) or non-Muse MSC groups, the Muse group showed significantly higher laser doppler blood flow in the ischemic limb at days 7 and 14 after HLI. Increased microvascular density [percent area of CD31(+) cells] and reduced interstitial fibrosis in the ischemic limb muscle were also observed in the Muse group. mCherry-expressing Muse cells were found in the ischemic border zone and expressed CD31 but did not in the non-ischemic limb. Muse cells produced higher amounts of vascular endothelial growth factor (VEGF) than non-Muse cells under normoxic and hypoxic conditions in vitro. In the ischemic muscle, tissue VEGF concentration and angiogenesis-related genes such as Vegfa, Angpt1, Pdgfb, and Igf1 were significantly higher in the Muse group than in the other two groups. In addition, the proportion of M2 macrophages to total macrophages and the ratio of anti-inflammatory-related genes such as IL-10, Arg1, and CD206 per iNOS were significantly higher in the Muse group than in the other two groups. In summary, Muse cells exert pleiotropic effects in a mouse model of HLI, and therefore may provide a novel therapeutic approach for the treatment of PAD patients with severe limb ischemia.

  13. Intravenous injection of human multilineage-differentiating stress-enduring cells alleviates mouse severe acute pancreatitis without immunosuppressants Peer-reviewed

    Masahiko Fukase, Naoaki Sakata, Yoshihiro Kushida, Shohei Wakao, Michiaki Unno, Mari Dezawa

    Surgery Today　52　(4)　603-615　2021/10/23

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1007/s00595-021-02382-7 　

    ISSN： 0941-1291

    eISSN： 1436-2813

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    INTRODUCTION: We examined the effect of intravenously injected human multilineage-differentiating stress-enduring (Muse) cells, non-tumorigenic endogenous reparative stem cells already used in clinical trials, on a severe acute pancreatitis (SAP) mouse model without immunosuppressants. METHODS: Human Muse cells (1.0 × 105 cells) collected from mesenchymal stem cells (MSCs) as SSEA-3(+) were injected into a C57BL/6 mouse model via the jugular vein 6 h after SAP-induction with taurocholate. The control group received saline or the same number of SSEA-3(-)-non-Muse MSCs. RESULTS: Edematous parameters, F4/80(+) macrophage infiltration and terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity was the lowest and the number of proliferating endogenous pancreatic progenitors (CK18(+)/Ki67(+) cells) the highest in the Muse group among the three groups, with statistical significance, at 72 h. An enzyme-linked immunosorbent assay and quantitative polymerase chain reaction demonstrated that in vitro production of VEGF, HGF, IGF-1, and MMP-2, which are relevant to tissue protection, anti-inflammation, and anti-fibrosis, were higher in Muse cells than in non-Muse MSCs, particularly when cells were cultured in SAP mouse serum. Consistently, the pancreas of animals in the Muse group contained higher amounts of those factors according to Western blotting at 18 h than that in the non-Muse MSCs and control groups. CONCLUSIONS: Intravenous injection of human Muse cells was suggested to be effective for attenuating edema, inflammation and apoptosis in the acute phase of SAP.

  14. Isolation and characterization of bone marrow-derived mesenchymal stem cells in Xenopus laevis. International-journal Peer-reviewed

    Rina Otsuka-Yamaguchi, Masaaki Kitada, Yasumasa Kuroda, Yoshihiro Kushida, Shohei Wakao, Mari Dezawa

    Stem cell research　53　102341-102341　2021/05

    DOI： 10.1016/j.scr.2021.102341 　

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    Mesenchymal stem cells (MSCs) are multipotent cells that exist in mesenchymal tissues such as bone marrow and are able to differentiate into osteocytes, chondrocytes, and adipocytes. MSCs are generally collected as adherent cells on a plastic dish, and are positive for markers such as CD44, CD73, CD90, CD105 and CD166, and negative for CD11b, CD14, CD19, CD31, CD34, CD45, CD79a and HLA-DR. MSCs have been established from many kinds of mammals, but MSCs from amphibians have not yet been reported. We cultured adherent cells from the bone marrow of Xenopus laevis by modifying the protocol for culturing mammalian MSCs. The morphology of these cells was similar to that of mammalian MSCs. The amphibian MSCs were positive for cd44, cd73, cd90 and cd166, and negative for cd11b, cd14, cd19, cd31, cd34, cd45, cd79a and hla-dra. Moreover, they could be induced to differentiate into osteocyte-, chondrocyte-, and adipocyte-lineage cells by cytokine induction systems that were similar to those used for mammalian MSC differentiation. Thus, they are considered to be similar to mammalian MSCs. Unlike mammals, amphibians have high regenerative capacity. The findings from the present study will allow for future research to reveal how Xenopus MSCs are involved in the amphibian regenerative capacity and to elucidate the differences in the regenerative capacity between mammals and amphibians.

  15. Non-Tumorigenic Pluripotent Reparative Muse Cells Provide a New Therapeutic Approach for Neurologic Diseases. International-journal Peer-reviewed

    Toru Yamashita, Yoshihiro Kushida, Koji Abe, Mari Dezawa

    Cells　10　(4)　961　2021/04/20

    DOI： 10.3390/cells10040961 　

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    Muse cells are non-tumorigenic endogenous reparative pluripotent cells with high therapeutic potential. They are identified as cells positive for the pluripotent surface marker SSEA-3 in the bone marrow, peripheral blood, and connective tissue. Muse cells also express other pluripotent stem cell markers, are able to differentiate into cells representative of all three germ layers, self-renew from a single cell, and are stress tolerant. They express receptors for sphingosine-1-phosphate (S1P), which is actively produced by damaged cells, allowing circulating cells to selectively home to damaged tissue. Muse cells spontaneously differentiate on-site into multiple tissue-constituent cells with few errors and replace damaged/apoptotic cells with functional cells, thereby contributing to tissue repair. Intravenous injection of exogenous Muse cells to increase the number of circulating Muse cells enhances their reparative activity. Muse cells also have a specific immunomodulatory system, represented by HLA-G expression, allowing them to be directly administered without HLA-matching or immunosuppressant treatment. Owing to these unique characteristics, clinical trials using intravenously administered donor-Muse cells have been conducted for myocardial infarction, stroke, epidermolysis bullosa, spinal cord injury, perinatal hypoxic ischemic encephalopathy, and amyotrophic lateral sclerosis. Muse cells have the potential to break through the limitations of current cell therapies for neurologic diseases, including amyotrophic lateral sclerosis. Muse cells provide a new therapeutic strategy that requires no HLA-matching or immunosuppressant treatment for administering donor-derived cells, no gene introduction or differentiation induction for cell preparation, and no surgery for delivering the cells to patients.

  16. The evaluation of the safety and efficacy of intravenously administered allogeneic multilineage-differentiating stress-enduring cells in a swine hepatectomy model Peer-reviewed

    Masahiro Iseki, Masamichi Mizuma, Shohei Wakao, Yoshihiro Kushida, Katsuyoshi Kudo, Masahiko Fukase, Masaharu Ishida, Tomoyuki Ono, Mitsuhiro Shimura, Ichiro Ise, Yukie Suzuki, Teruko Sueta, Ryuta Asada, Shinobu Shimizu, Yoshiyuki Ueno, Mari Dezawa, Michiaki Unno

    Surgery Today　51　(4)　634-650　2021/04

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1007/s00595-020-02117-0 　

    ISSN： 0941-1291

    eISSN： 1436-2813

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    INTRODUCTION: Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic endogenous pluripotent-like cells residing in the bone marrow that exert a tissue reparative effect by replacing damaged/apoptotic cells through spontaneous differentiation into tissue-constituent cells. Post-hepatectomy liver failure (PHLF) is a potentially fatal complication. The main purpose of this study was to evaluate the safety and efficiency of allogeneic Muse cell administration via the portal vein in a swine model of PHLF. METHODS: Swine Muse cells, collected from swine bone marrow-mesenchymal stem cells (MSCs) as SSEA-3(+) cells, were examined for their characteristics. Then, 1 × 107 allogeneic-Muse cells and allogeneic-MSCs and vehicle were injected via the portal vein in a 70% hepatectomy swine model. RESULTS: Swine Muse cells exhibited characteristics comparable to previously reported human Muse cells. Compared to the MSC and vehicle groups, the Muse group showed specific homing of the administered cells into the liver, resulting in improvements in the control of hyperbilirubinemia (P = 0.04), prothrombin international normalized ratio (P = 0.05), and suppression of focal necrosis (P = 0.04). Integrated Muse cells differentiated spontaneously into hepatocyte marker-positive cells. CONCLUSIONS: Allogeneic Muse cell administration may provide a reparative effect and functional recovery in a 70% hepatectomy swine model and thus may contribute to the treatment of PHLF.

  17. Comparison of separation methods for tissue‐derived extracellular vesicles in the liver, heart, and skeletal muscle Peer-reviewed

    Adam Matejovič, Shohei Wakao, Masaaki Kitada, Yoshihiro Kushida, Mari Dezawa

    FEBS Open Bio　11　(2)　482-493　2021/01/29

    Publisher: Wiley

    DOI： 10.1002/2211-5463.13075 　

    ISSN： 2211-5463

    eISSN： 2211-5463

  18. Protection of liver sinusoids by intravenous administration of human Muse cells in a rat extra‐small partial liver transplantation model International-journal Peer-reviewed

    Yoshihiro Shono, Yoshihiro Kushida, Shohei Wakao, Yasumasa Kuroda, Michiaki Unno, Takashi Kamei, Shigehito Miyagi, Mari Dezawa

    American Journal of Transplantation　21　(6)　2025-2039　2021/01/15

    Publisher: Wiley

    DOI： 10.1111/ajt.16461 　

    ISSN： 1600-6135

    eISSN： 1600-6143

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    Small-for-size syndrome (SFSS) has a poor prognosis due to excessive shear stress and sinusoidal microcirculatory disturbances in the acute phase after living-donor liver transplantation (LDLT). Multilineage-differentiating stress enduring (Muse) cells are reparative stem cells found in various tissues and currently under clinical trials. These cells selectively home to damaged sites via the sphingosine-1-phosphate (S1P)-S1P receptor 2 system and repair damaged tissue by pleiotropic effects, including tissue protection and damaged/apoptotic cell replacement by differentiating into tissue-constituent cells. The effects of intravenously administered human bone marrow-Muse cells and -mesenchymal stem cells (MSCs) (4 × 105 ) on liver sinusoidal endothelial cells (LSECs) were examined in a rat SFSS model without immunosuppression. Compared with MSCs, Muse cells intensively homed to the grafted liver, distributed to the sinusoids and vessels, and delivered improved blood chemistry and Ki-67(+) proliferative hepatocytes and -LSECs within 3 days. Tissue clearing and three-dimensional imaging by multiphoton laser confocal microscopy revealed maintenance of the sinusoid continuity, organization, and surface area, as well as decreased sinusoid interruption in the Muse group. Small-interfering RNA-induced knockdown of hepatocyte growth factor and vascular endothelial growth factor-A impaired the protective effect of Muse cells on LSECs. Intravenous injection of Muse cells might be a feasible approach for LDLT with less recipient burden.

  19. Intravenous Injection of Muse Cells as a Potential Therapeutic Approach for Epidermolysis Bullosa. International-journal Peer-reviewed

    Yasuyuki Fujita, Miho Komatsu, San Eun Lee, Yoshihiro Kushida, Chihiro Nakayama-Nishimura, Wakana Matsumura, Shota Takashima, Satoru Shinkuma, Toshifumi Nomura, Naoya Masutomi, Makoto Kawamura, Mari Dezawa, Hiroshi Shimizu

    The Journal of investigative dermatology　141　(1)　198-202　2021

    DOI： 10.1016/j.jid.2020.05.092 　

  20. Therapeutic benefit of Muse cells in a mouse model of amyotrophic lateral sclerosis International-journal Peer-reviewed

    Toru Yamashita, Yoshihiro Kushida, Shohei Wakao, Koh Tadokoro, Emi Nomura, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Mari Dezawa, Koji Abe

    Scientific Reports　10　(1)　17102-17102　2020/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41598-020-74216-4 　

    eISSN： 2045-2322

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    <title>Abstract</title> Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss. Muse cells are endogenous reparative pluripotent-like stem cells distributed in various tissues. They can selectively home to damaged sites after intravenous injection by sensing sphingosine-1-phosphate produced by damaged cells, then exert pleiotropic effects, including tissue protection and spontaneous differentiation into tissue-constituent cells. In G93A-transgenic ALS mice, intravenous injection of 5.0 × 104 cells revealed successful homing of human-Muse cells to the lumbar spinal cords, mainly at the pia-mater and underneath white matter, and exhibited glia-like morphology and GFAP expression. In contrast, such homing or differentiation were not recognized in human mesenchymal stem cells but were instead distributed mainly in the lung. Relative to the vehicle groups, the Muse group significantly improved scores in the rotarod, hanging-wire and muscle strength of lower limbs, recovered the number of motor neurons, and alleviated denervation and myofiber atrophy in lower limb muscles. These results suggest that Muse cells homed in a lesion site-dependent manner and protected the spinal cord against motor neuron death. Muse cells might also be a promising cell source for the treatment of ALS patients.

  21. Intravenously delivered multilineage-differentiating stress enduring cells dampen excessive glutamate metabolism and microglial activation in experimental perinatal hypoxic ischemic encephalopathy Peer-reviewed

    Toshihiko Suzuki, Yoshiaki Sato, Yoshihiro Kushida, Masahiro Tsuji, Shohei Wakao, Kazuto Ueda, Kenji Imai, Yukako Iitani, Shinobu Shimizu, Hideki Hida, Takashi Temma, Shigeyoshi Saito, Hidehiro Iida, Masaaki Mizuno, Yoshiyuki Takahashi, Mari Dezawa, Cesar V Borlongan, Masahiro Hayakawa

    Journal of Cerebral Blood Flow & Metabolism　41　(7)　1707-1720　2020/11/22

    Publisher: SAGE Publications

    DOI： 10.1177/0271678x20972656 　

    ISSN： 0271-678X

    eISSN： 1559-7016

  22. Intravenously Transplanted Human Multilineage-Differentiating Stress-Enduring Cells Afford Brain Repair in a Mouse Lacunar Stroke Model. International-journal Peer-reviewed

    Takatsugu Abe, Daiki Aburakawa, Kuniyasu Niizuma, Naoya Iwabuchi, Takumi Kajitani, Shohei Wakao, Yoshihiro Kushida, Mari Dezawa, Cesar V Borlongan, Teiji Tominaga

    Stroke　51　(2)　601-611　2020/02

    DOI： 10.1161/STROKEAHA.119.026589 　

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    Background and Purpose- Multilineage-differentiating stress-enduring cells are endogenous nontumorigenic reparative pluripotent-like stem cells found in bone marrow, peripheral blood, and connective tissues. Topically administered human multilineage-differentiating stress-enduring cells into rat/mouse stroke models differentiated into neural cells and promoted clinically relevant functional recovery. However, critical questions on the appropriate timing and dose, and safety of the less invasive intravenous administration of clinical-grade multilineage-differentiating stress-enduring cell-based product CL2020 remain unanswered. Methods- Using an immunodeficient mouse lacunar model, CL2020 was administered via the cervical vein in different doses (high dose=5×104 cells/body; medium dose=1×104 cells/body; low dose=5×103 cells/body) at subacute phase (≈9 days after onset) and chronic phase (≈30 days). Cylinder test, depletion of human cells by diphtheria toxin administration, immunohistochemistry, and human specific-genome detection were performed. Results- Tumorigenesis and adverse effects were not detected for up to 22 weeks. The high-dose group displayed significant functional recovery compared with the vehicle group in cylinder test in subacute-phase-treated and chronic-phase-treated animals after 6 weeks and 8 weeks post-injection, respectively. In the high-dose group of subacute-phase-treated animals, robust and stable recovery in cylinder test persisted up to 22 weeks compared with the vehicle group. In both groups, intraperitoneal injection of diphtheria toxin abrogated the functional recovery. Anti-human mitochondria revealed CL2020 distributed mainly in the peri-infarct area at 1, 10, and 22 weeks and expressed NeuN (neuronal nuclei)- and MAP-2 (microtubule-associated protein-2)-immunoreactivity. Conclusions- Intravenously administered CL2020 was safe, migrated to the peri-infarct area, and afforded functional recovery in experimental stroke.

  23. A Novel Type of Stem Cells Double-Positive for SSEA-3 and CD45 in Human Peripheral Blood Peer-reviewed

    Tetsuya Sato, Shohei Wakao, Yoshihiro Kushida, Kazuki Tatsumi, Masaaki Kitada, Takatsugu Abe, Kuniyasu Niizuma, Teiji Tominaga, Shigeki Kushimoto, Mari Dezawa

    Cell Transplantation　29　096368972092357-096368972092357　2020/01/01

    Publisher: SAGE Publications

    DOI： 10.1177/0963689720923574 　

    ISSN： 0963-6897

    eISSN： 1555-3892

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    Peripheral blood (PB) contains several types of stem/progenitor cells, including hematopoietic stem and endothelial progenitor cells. We identified a population positive for both the pluripotent surface marker SSEA-3 and leukocyte common antigen CD45 that comprises 0.04% ± 0.003% of the mononuclear cells in human PB. The average size of the SSEA-3(+)/CD45(+) cells was 10.1 ± 0.3 µm and ∼22% were positive for CD105, a mesenchymal marker; ∼85% were positive for CD19, a B cell marker; and ∼94% were positive for HLA-DR, a major histocompatibility complex class II molecule relevant to antigen presentation. These SSEA-3(+)/CD45(+) cells expressed the pluripotency markers Nanog, Oct3/4, and Sox2, as well as sphingosine-1-phosphate (S1P) receptor 2, and migrated toward S1P, although their adherence and proliferative activities in vitro were low. They expressed NeuN at 7 d, Pax7 and desmin at 7 d, and alpha-fetoprotein and cytokeratin-19 at 3 d when supplied to mouse damaged tissues of the brain, skeletal muscle and liver, respectively, suggesting the ability to spontaneously differentiate into triploblastic lineages compatible to the tissue microenvironment. Multilineage-differentiating stress enduring (Muse) cells, identified as SSEA-3(+) in tissues such as the bone marrow and organ connective tissues, express pluripotency markers, migrate to sites of damage via the S1P-S1P receptor 2 system, and differentiate spontaneously into tissue-compatible cells after homing to the damaged tissue where they participate in tissue repair. After the onset of acute myocardial infarction and stroke, patients are reported to have an increase in the number of SSEA-3(+) cells in the PB. The SSEA-3(+)/CD45(+) cells in the PB showed similarity to tissue-Muse cells, although with difference in surface marker expression and cellular properties. Thus, these findings suggest that human PB contains a subset of cells that are distinct from known stem/progenitor cells, and that CD45(+)-mononuclear cells in the PB comprise a novel subpopulation of cells that express pluripotency markers.

  24. Quantitative Analysis of SSEA3+ Cells from Human Umbilical Cord after Magnetic Sorting Peer-reviewed

    Zikuan Leng, Dongming Sun, Zihao Huang, Iman Tadmori, Ning Chiang, Nikhit Kethidi, Ahmed Sabra, Yoshihiro Kushida, Yu-Show Fu, Mari Dezawa, Xijing He, Wise Young

    Cell Transplantation　28　(7)　907-923　2019/04/18

    Publisher: SAGE Publications

    DOI： 10.1177/0963689719844260 　

    ISSN： 0963-6897

    eISSN： 1555-3892

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    Multilineage-differentiating stress-enduring (Muse) cells are a population of pluripotent stage-specific embryonic antigen 3 (SSEA3)+ mesenchymal stem cells first described by Mari Dezawa in 2010. Although some investigators have reported SSEA3+ mesenchymal cells in umbilical cord tissues, none have quantitatively compared SSEA3+ cells isolated from Wharton’s jelly (WJ) and the cord lining (CL) of human umbilical cords (HUCs). We separated WJ and the CL from HUCs, cultured mesenchymal stromal cells (MSCs) isolated from these two tissues with collagenase, and quantified the percentage of SSEA3+ cells over three passages. The first passage had 5.0% ± 4.3% and 5.3% ± 5.1% SSEA3+ cells from WJ and the CL, respectively, but the percentage of SSEA3+ cells decreased significantly ( P &lt; 0.05) between P0 and P2 in the CL group and between P0 and P1 in the WJ group. Magnetic-activated cell sorting (MACS) markedly enriched SSEA3+ cells to 91.4% ± 3.2%. Upon culture of the sorted population, we found that the SSEA3+ percentage ranged from 62.5% to 76.0% in P2–P5 and then declined to 42.0%–54.7% between P6 and P9. At P10, the cultures contained 37.4% SSEA3+ cells. After P10, we resorted the cells and achieved 89.4% SSEA3+ cells in culture. The procedure for MACS-based enrichment of SSEA3+ cells, followed by expansion in culture and a re-enrichment step, allows the isolation of many millions of SSEA3+ cells in relatively pure culture. When cultured, the sorted SSEA3+ cells differentiated into embryoid spheres and survived 4 weeks after transplant into a contused Sprague-Dawley rat spinal cord. The transplanted SSEA3+ cells migrated into the injury area from four injection points around the contusion site and did not produce any tumors. The umbilical cord is an excellent source of fetal Muse cells, and our method allows the practical and efficient isolation and expansion of relatively pure populations of SSEA3+ Muse cells that can be matched by human leukocyte antigen for transplantation in human trials.

  25. Basic Characteristics of Muse Cells

    Shohei Wakao, Yoshihiro Kushida, Mari Dezawa

    Advances in Experimental Medicine and Biology　13-41　2018/11/28

    Publisher: Springer Japan

    DOI： 10.1007/978-4-431-56847-6_2 　

    ISSN： 0065-2598

    eISSN： 2214-8019

  26. Muse Cells Are Endogenous Reparative Stem Cells

    Yoshihiro Kushida, Shohei Wakao, Mari Dezawa

    Advances in Experimental Medicine and Biology　43-68　2018/11/28

    Publisher: Springer Japan

    DOI： 10.1007/978-4-431-56847-6_3 　

    ISSN： 0065-2598

    eISSN： 2214-8019

  27. Protocols for Isolation and Evaluation of Muse Cells

    Kazuki Tatsumi, Yoshihiro Kushida, Shohei Wakao, Yasumasa Kuroda, Mari Dezawa

    Advances in Experimental Medicine and Biology　69-101　2018/11/28

    Publisher: Springer Japan

    DOI： 10.1007/978-4-431-56847-6_4 　

    ISSN： 0065-2598

    eISSN： 2214-8019

  28. Intravenously injected human multilineage-differentiating stress-enduring cells selectively engraft into mouse aortic aneurysms and attenuate dilatation by differentiating into multiple cell types Peer-reviewed

    Katsuhiro Hosoyama, Shohei Wakao, Yoshihiro Kushida, Fumitaka Ogura, Kay Maeda, Osamu Adachi, Shunsuke Kawamoto, Mari Dezawa, Yoshikatsu Saiki

    Journal of Thoracic and Cardiovascular Surgery　155　(6)　2301-2313.e4　2018/06/01

    Publisher: Mosby Inc.

    DOI： 10.1016/j.jtcvs.2018.01.098 　

    ISSN： 1097-685X 0022-5223

    eISSN： 1097-685X

  29. Human Multilineage-differentiating Stress-Enduring Cells Exert Pleiotropic Effects to Ameliorate Acute Lung Ischemia–Reperfusion Injury in a Rat Model Peer-reviewed

    Hiroshi Yabuki, Shohei Wakao, Yoshihiro Kushida, Mari Dezawa, Yoshinori Okada

    Cell Transplantation　27　(6)　979-993　2018/04/30

    Publisher: SAGE Publications

    DOI： 10.1177/0963689718761657 　

    ISSN： 0963-6897

    eISSN： 1555-3892

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    Posttransplantation lung ischemia–reperfusion (IR) injuries affect both patient survival and graft function. In this study, we evaluated the protective effects of infused human multilineage-differentiating stress-enduring (Muse) cells, a novel, easily harvested type of nontumorigenic endogenous reparative stem cell, against acute IR lung injury in a rat model. After a 2-h warm IR injury induction in a left rat lung, human Muse cells, human mesenchymal stem cells (MSCs), and vehicle were injected via the left pulmonary artery after reperfusion. Functionality, histological findings, and protein expression were subsequently assessed in the injured lung. In vitro, we also compared human Muse cells with human MSCs in terms of migration abilities and the secretory properties of protective substances. The arterial oxygen partial pressure to fractional inspired oxygen ratio, alveolar-arterial oxygen gradient, left lung compliance, and histological injury score on hematoxylin–eosin sections were significantly better in the Muse group relative to the MSC and vehicle groups. Compared to MSCs, human Muse cells homed more efficiently to the injured lung, where they suppressed the apoptosis and stimulated proliferation of host alveolar cells. Human Muse cells also migrated to serum from lung-injured model rats and produced beneficial substances (keratinocyte growth factor [KGF], hepatocyte growth factor, angiopoietin-1, and prostaglandin E2) in vitro. Western blot of lung tissue confirmed high expression of KGF and their target molecules (interleukin-6, protein kinase B, and B-cell lymphoma-2) in the Muse group. Thus, Muse cells efficiently ameliorated lung IR injury via pleiotropic effects in a rat model. These findings support further investigation on the use of human Muse cells for lung IR injury.

  30. S1P–S1PR2 Axis Mediates Homing of Muse Cells Into Damaged Heart for Long-Lasting Tissue Repair and Functional Recovery After Acute Myocardial Infarction Peer-reviewed

    Yoshihisa Yamada, Shohei Wakao, Yoshihiro Kushida, Shingo Minatoguchi, Atsushi Mikami, Kenshi Higashi, Shinya Baba, Taeko Shigemoto, Yasumasa Kuroda, Hiromitsu Kanamori, Mohamad Amin, Masanori Kawasaki, Kazuhiko Nishigaki, Masato Taoka, Toshiaki Isobe, Chisako Muramatsu, Mari Dezawa, Shinya Minatoguchi

    Circulation Research　122　(8)　1069-1083　2018/04/13

    Publisher: Ovid Technologies (Wolters Kluwer Health)

    DOI： 10.1161/circresaha.117.311648 　

    ISSN： 0009-7330

    eISSN： 1524-4571

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    Rationale: Multilineage-differentiating stress enduring (Muse) cells, pluripotent marker stage-specific embryonic antigen-3 + cells, are nontumorigenic endogenous pluripotent-like stem cells obtainable from various tissues including the bone marrow. Their therapeutic efficiency has not been validated in acute myocardial infarction. Objective: The main objective of this study is to clarify the efficiency of intravenously infused rabbit autograft, allograft, and xenograft (human) bone marrow-Muse cells in a rabbit acute myocardial infarction model and their mechanisms of tissue repair. Methods and Results: In vivo dynamics of Nano-lantern–labeled Muse cells showed preferential homing of the cells to the postinfarct heart at 3 days and 2 weeks, with ≈14.5% of injected GFP (green fluorescent protein)-Muse cells estimated to be engrafted into the heart at 3 days. The migration and homing of the Muse cells was confirmed pharmacologically (S1PR2 [sphingosine monophosphate receptor 2]–specific antagonist JTE-013 coinjection) and genetically (S1PR2-siRNA [small interfering ribonucleic acid]–introduced Muse cells) to be mediated through the S1P (sphingosine monophosphate)–S1PR2 axis. They spontaneously differentiated into cells positive for cardiac markers, such as cardiac troponin-I, sarcomeric α-actinin, and connexin-43, and vascular markers. GCaMP3 (GFP-based Ca calmodulin probe)-labeled Muse cells that engrafted into the ischemic region exhibited increased GCaMP3 fluorescence during systole and decreased fluorescence during diastole. Infarct size was reduced by ≈52%, and the ejection fraction was increased by ≈38% compared with vehicle injection at 2 months, ≈2.5 and ≈2.1 times higher, respectively, than that induced by mesenchymal stem cells. These effects were partially attenuated by the administration of GATA4 -gene–silenced Muse cells. Muse cell allografts and xenografts efficiently engrafted and recovered functions, and allografts remained in the tissue and sustained functional recovery for up to 6 months without immunosuppression. Conclusions: Muse cells may provide reparative effects and robust functional recovery and may, thus, provide a novel strategy for the treatment of acute myocardial infarction.

  31. Cardiotrophic Growth Factor–Driven Induction of Human Muse Cells Into Cardiomyocyte-Like Phenotype Peer-reviewed

    Mohamed Amin, Yoshihiro Kushida, Shohei Wakao, Masaaki Kitada, Kazuki Tatsumi, Mari Dezawa

    Cell Transplantation　27　(2)　285-298　2018/02/01

    Publisher: SAGE Publications Ltd

    DOI： 10.1177/0963689717721514 　

    ISSN： 1555-3892 0963-6897

  32. Beneficial Effects of Systemically Administered Human Muse Cells in Adriamycin Nephropathy Peer-reviewed

    Nao Uchida, Yoshihiro Kushida, Masaaki Kitada, Shohei Wakao, Naonori Kumagai, Yasumasa Kuroda, Yoshiaki Kondo, Yukari Hirohara, Shigeo Kure, Gregorio Chazenbalk, Mari Dezawa

    Journal of the American Society of Nephrology　28　(10)　2946-2960　2017/07/03

    DOI： 10.1681/asn.2016070775 　

    ISSN： 1046-6673

    eISSN： 1533-3450

  33. Human Muse Cells, Nontumorigenic Phiripotent-Like Stem Cells, Have Liver Regeneration Capacity through Specific Homing and Cell Replacement in a Mouse Model of Liver Fibrosis Peer-reviewed

    Masahiro Iseki, Yoshihiro Kushida, Shohei Wakao, Takahiro Akimoto, Masamichi Mizuma, Fuyuhiko Motoi, Ryuta Asada, Shinobu Shimizu, Michiaki Unno, Gregorio Chazenbalk, Mari Dezawa

    Cell Transplantation　26　(5)　821-840　2017/05/01

    DOI： 10.3727/096368916x693662 　

    ISSN： 0963-6897

    eISSN： 1555-3892

  34. Human Muse Cells Reconstruct Neuronal Circuitry in Subacute Lacunar Stroke Model Peer-reviewed

    Hiroki Uchida, Kuniyasu Niizuma, Yoshihiro Kushida, Shohei Wakao, Teiji Tominaga, Cesario V. Borlongan, Mari Dezawa

    Stroke　48　(2)　428-435　2017/02

    DOI： 10.1161/strokeaha.116.014950 　

    ISSN： 0039-2499

    eISSN： 1524-4628

  35. A Distinct Subpopulation of Bone Marrow Mesenchymal Stem Cells, Muse Cells, Directly Commit to the Replacement of Liver Components Peer-reviewed

    H. Katagiri, Y. Kushida, M. Nojima, Y. Kuroda, S. Wakao, K. Ishida, F. Endo, K. Kume, T. Takahara, H. Nitta, H. Tsuda, M. Dezawa, S.S. Nishizuka

    American Journal of Transplantation　16　(2)　468-483　2016/02

    DOI： 10.1111/ajt.13537 　

    ISSN： 1600-6135

    eISSN： 1600-6143

  36. Induction of autoimmune gastritis by neonatal thymectomy requires autoantibodies and is prevented by anti-FcγR antibodies Peer-reviewed

    Tsubasa Saito, Satoru Suenaga, Masato Fujii, Yoshihiro Kushida, Yusuke Kawauchi, Kenji Suzuki, Maki Touma, Masamichi Hosono

    Cellular Immunology　300　1-8　2016/02

    DOI： 10.1016/j.cellimm.2015.10.004 　

    ISSN： 0008-8749

    eISSN： 1090-2163

  37. Experimental model of small subcortical infarcts in mice with long-lasting functional disabilities Peer-reviewed

    Hiroki Uchida, Hiroyuki Sakata, Miki Fujimura, Kuniyasu Niizuma, Yoshihiro Kushida, Mari Dezawa, Teiji Tominaga

    Brain Research　1629　318-328　2015/12

    DOI： 10.1016/j.brainres.2015.10.039 　

    ISSN： 0006-8993

    eISSN： 1872-6240

  38. Transplantation of Unique Subpopulation of Fibroblasts, Muse Cells, Ameliorates Experimental Stroke Possibly via Robust Neuronal Differentiation Peer-reviewed

    Hiroki Uchida, Takahiro Morita, Kuniyasu Niizuma, Yoshihiro Kushida, Yasumasa Kuroda, Shohei Wakao, Hiroyuki Sakata, Yoshiya Matsuzaka, Hajime Mushiake, Teiji Tominaga, Cesario V. Borlongan, Mari Dezawa

    Stem Cells　34　(1)　160-173　2015/09/28

    DOI： 10.1002/stem.2206 　

    ISSN： 1066-5099

    eISSN： 1549-4918

  39. Population doublings of murine CD4+ memory T cells during continuous antigen stimulation in vivo Peer-reviewed

    Yoshihiro Kushida, Jun-ya Ishida, Masato Fujii, Maki Touma, Masamichi Hosono

    Cellular Immunology　292　(1-2)　45-52　2014/11

    DOI： 10.1016/j.cellimm.2014.09.001 　

    ISSN： 0008-8749

    eISSN： 1090-2163

  40. Muse cells, newly found non-tumorigenic pluripotent stem cells, reside in human mesenchymal tissues Peer-reviewed

    Shohei Wakao, Hideo Akashi, Yoshihiro Kushida, Mari Dezawa

    Pathology International　64　(1)　1-9　2014/01/29

    DOI： 10.1111/pin.12129 　

    ISSN： 1320-5463

    eISSN： 1440-1827

  41. A Dominant Trait Linked to Chromosome 1 in DBA/2 Mice for the Resistance to Autoimmune Gastritis Appears in Bone Marrow Cells Peer-reviewed

    Masato Fujii, Kenji Suzuki, Satoru Suenaga, Mariko Wakatsuki, Yoshihiro Kushida, Maki Touma, Masamichi Hosono

    Experimental Animals　63　(2)　155-167　2014

    DOI： 10.1538/expanim.63.155 　

    ISSN： 1341-1357

    eISSN： 1881-7122

  42. Limited Immune Diversity in Urodela: Chronic Transplantation Responses Occur Even with Family-disparate Xenografts Peer-reviewed

    Kenjiroh Kinefuchi, Yoshihiro Kushida, Maki Touma, Masamichi Hosono

    Zoological Science　30　(7)　577-584　2013/07

    Publisher: Zoological Society of Japan

    DOI： 10.2108/zsj.30.577 　

    ISSN： 0289-0003

  43. T cells affect thymic involution during puberty by inducing regression of the adrenal reticularis Peer-reviewed

    Yoshihiro Kushida, Sayaka Kumagai, Ken Gotoh, Masato Fujii, Maki Touma, Masamichi Hosono

    The Journal of Physiological Sciences　62　(3)　173-184　2012/02/14

    DOI： 10.1007/s12576-012-0194-y 　

    ISSN： 1880-6546

    eISSN： 1880-6562

  44. Chronic Transplantation Immunity in Newts: Temperature Susceptibility of an Effector Phase in Allo-Skin Graft Rejection Peer-reviewed

    Kenjiroh Kinefuchi, Yoshihiro Kushida, Masato Johnouchi, Yuiko Shimizu, Hikaru Ohneda, Masato Fujii, Masamichi Hosono

    Zoological Science　28　(7)　509-516　2011/07

    DOI： 10.2108/zsj.28.509 　

    ISSN： 0289-0003

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Misc. 35

  1. 皮膚科にも来た再生医療 生体内修復幹細胞としてのMuse細胞の可能性

    串田 良祐

    日本臨床皮膚科医会雑誌　40　(3)　340-340　2023/05

    Publisher: 日本臨床皮膚科医会

    ISSN： 1349-7758

    eISSN： 1882-272X

  2. ラット極小肝移植モデルへのMuse細胞の静脈投与が及ぼすHGF/VEGFAによる肝類洞保護効果について

    菖野 佳浩, 串田 良祐, 若尾 昌平, 黒田 康勝, 海野 倫明, 亀井 尚, 宮城 重人, 出澤 真理

    日本外科学会定期学術集会抄録集　122回　SF-2　2022/04

    Publisher: (一社)日本外科学会

  3. ラット過小グラフト肝移植モデルに対するヒトMuse細胞静脈投与による肝類洞微小循環改善効果について

    菖野 佳浩, 串田 良祐, 黒田 康勝, 若尾 昌平, 海野 倫明, 亀井 尚, 宮城 重人, 出澤 真理

    日本消化器外科学会総会　76回　P143-3　2021/07

    Publisher: (一社)日本消化器外科学会

  4. マウスラクナ梗塞モデルに対するMuse細胞製品CL2020の治療効果の検討

    阿部 考貢, 油川 大輝, 新妻 邦泰, 串田 良祐, 若尾 昌平, 出澤 真理, 冨永 悌二

    脳循環代謝　32　(1)　99-99　2020/11

    Publisher: (一社)日本脳循環代謝学会

    ISSN： 0915-9401

    eISSN： 2188-7519

  5. 再生医療の実現-外科医に期待される役割- ブタ70%肝切除モデルに対する経門脈同種Muse細胞移植

    伊関 雅裕, 水間 正道, 深瀬 正彦, 小野 智之, 志村 充広, 鈴木 ゆき恵, 伊勢 一郎, 石田 晶玄, 工藤 克昌, 林 洋毅, 元井 冬彦, 若尾 昌平, 串田 良祐, 亀井 尚, 石田 孝宣, 内藤 剛, 出澤 真理, 海野 倫明

    日本外科学会定期学術集会抄録集　120回　WS-2　2020/08

    Publisher: (一社)日本外科学会

  6. マウスラクナ梗塞モデルに対するMuse細胞含有製剤CL2020の治療効果の検討

    阿部考貢, 油川大輝, 新妻邦泰, 串田良祐, 若尾昌平, 出澤真理, 冨永悌二

    日本異種移植研究会プログラム・抄録集　22nd (CD-ROM)　2020

  7. 肝再生におけるMuse細胞移植の可能性

    伊関 雅裕, 水間 正道, 深瀬 正彦, 小野 智之, 志村 充宏, 鈴木 ゆき恵, 伊勢 一郎, 石田 晶玄, 工藤 克昌, 林 洋毅, 元井 冬彦, 若尾 昌平, 串田 良祐, 亀井 尚, 石田 孝宣, 内藤 剛, 出澤 真理, 海野 倫明

    日本外科学会定期学術集会抄録集　118回　1249-1249　2018/04

    Publisher: (一社)日本外科学会

  8. 肝再生におけるMuse細胞移植の可能性

    伊関 雅裕, 水間 正道, 深瀬 正彦, 小野 智之, 志村 充宏, 鈴木 ゆき恵, 伊勢 一郎, 石田 晶玄, 工藤 克昌, 林 洋毅, 元井 冬彦, 若尾 昌平, 串田 良祐, 亀井 尚, 石田 孝宣, 内藤 剛, 出澤 真理, 海野 倫明

    日本外科学会定期学術集会抄録集　118回　1249-1249　2018/04

    Publisher: (一社)日本外科学会

  9. Multilineage-differentiating stress enduring cellsを用いた新生児慢性肺疾患に対する新規治療法の開発

    佐藤 義朗, 鈴木 俊彦, 田中 雅人, 上田 一仁, 田中 亮, 三浦 良介, 呉 尚治, 浅田 英之, 北瀬 悠磨, 立花 貴史, 見松 はるか, 伊藤 美香, 齊藤 明子, 村松 友佳子, 早川 昌弘, 出澤 真理, 串田 良祐

    日本新生児成育医学会雑誌　29　(3)　589-589　2017/10

    Publisher: (公社)日本新生児成育医学会

    ISSN： 2189-7549

  10. 新生児慢性肺疾患に伴う肺高血圧症に対するMultilineage-differentiating stress enduring cellsを用いた新規治療法の開発

    鈴木 俊彦, 佐藤 義朗, 上田 一仁, 田中 雅人, 田中 亮, 三浦 良介, 呉 尚治, 浅田 英之, 北瀬 悠磨, 立花 貴史, 見松 はるか, 伊藤 美春, 齊藤 明子, 村松 友佳子, 早川 昌弘, 出澤 真理, 串田 良祐

    日本新生児成育医学会雑誌　29　(3)　611-611　2017/10

    Publisher: (公社)日本新生児成育医学会

    ISSN： 2189-7549

  11. ラット肺虚血再灌流障害モデルにおけるMuse細胞の有効性

    矢吹 皓, 若尾 昌平, 串田 良祐, 出澤 真理, 岡田 克典

    移植　52　(総会臨時)　490-490　2017/08

    Publisher: (一社)日本移植学会

    ISSN： 0578-7947

    eISSN： 2188-0034

  12. 臨床応用を目指した消化器外科領域の基礎研究・橋渡し研究 マウス肝障害モデルを用いたMuse細胞移植療法の検討

    伊関 雅裕, 若尾 昌平, 串田 良祐, 水間 正道, 深瀬 正彦, 林 洋毅, 元井 冬彦, 出澤 真理, 海野 倫明

    日本消化器外科学会総会　72回　WS14-11　2017/07

    Publisher: (一社)日本消化器外科学会

  13. Beneficial Pleiotropic Effects of Multilineage-Differentiating Stress Enduring Cells on Acute Lung Ischemia-Reperfusion Injury

    H. Yabuki, S. Wakao, Y. Kushida, M. Dezawa, Y. Okada

    JOURNAL OF HEART AND LUNG TRANSPLANTATION　36　(4)　S380-S380　2017/04

    ISSN： 1053-2498

    eISSN： 1557-3117

  14. 急性膵炎モデルマウスの作成とその定量評価法の確立 抗サイトカイン療法の実現へ向けての基礎実験

    深瀬 正彦, 坂田 直昭, 川口 桂, 若尾 昌平, 串田 良祐, 出澤 真理, 海野 倫明

    日本腹部救急医学会雑誌　37　(2)　222-222　2017/02

    Publisher: (一社)日本腹部救急医学会

    ISSN： 1340-2242

    eISSN： 1882-4781

  15. Muse細胞静脈内投与は血管構成細胞再生によりマウス大動脈瘤拡大を抑制する

    鷹谷紘樹, 細山勝寛, 若尾昌平, 串田良祐, 齋木佳克, 出澤真理

    再生医療　16　2017

    ISSN： 1347-7919

  16. Muse細胞投与はマウス急性膵炎モデルを改善する

    深瀬 正彦, 坂田 直昭, 串田 良祐, 若尾 昌平, 海野 倫明, 出澤 真理

    移植　51　(総会臨時)　320-320　2016/09

    Publisher: (一社)日本移植学会

    ISSN： 0578-7947

    eISSN： 2188-0034

  17. Sphingosine-1-phosphate mobilizes Muse cells, pluripotent stem cells, to replenish cardiomyocytes, reduce the infarct size, and recover the cardiac function after acute myocardial infarction

    S. Minatoguchi, Y. Yamada, S. Wakao, Y. Kushida, M. Iwasa, H. Kanamori, M. Kawasaki, K. Nishigaki, M. Dezawa, S. Minatoguchi

    EUROPEAN HEART JOURNAL　37　1167-1167　2016/08

    ISSN： 0195-668X

    eISSN： 1522-9645

  18. Active cardiac-targeted delivery of sphingosine-1-phosphate attracts Muse cells to the infarcted region and replenishes cardiomyocytes to recover the cardiac function after myocardial infarction

    S. Minatoguchi, Y. Yamada, S. Wakao, Y. Kushida, A. Mikami, H. Kanamori, M. Kawasaki, K. Nishigaki, M. Dezawa, S. Minatoguchi

    EUROPEAN HEART JOURNAL　37　180-180　2016/08

    ISSN： 0195-668X

    eISSN： 1522-9645

  19. 再生医学における組織細胞化学的アプローチ

    串田 良祐, 出澤 真理

    2016　29-34　2016/07

    Publisher: 日本組織細胞化学会

  20. 【近未来の呼吸器疾患治療】 基礎医学とのダイアローグ Muse細胞と再生医療への実現性

    出澤 真理, 串田 良祐, 若尾 昌平

    THE LUNG-perspectives　24　(2)　192-199　2016/05

    Publisher: (株)メディカルレビュー社

    ISSN： 0919-5742

  21. 細胞移植の新たな展開 臍帯組織中に存在する多能性幹細胞Muse細胞の多能性の解析

    串田 良祐, 若尾 昌平, 明石 英雄, 西村 範行, 岩谷 壮太, 香田 翼, 森岡 一朗, 溝渕 雅巳, 飯島 一誠, 出澤 真理

    Organ Biology　22　(3)　43-43　2015/10

    Publisher: (一社)日本臓器保存生物医学会

    ISSN： 1340-5152

    eISSN： 2188-0204

  22. 慢性腎臓病モデルに対するMuse細胞を用いた細胞治療の検討

    内田 奈生, 若尾 昌平, 串田 良祐, 熊谷 直憲, 出澤 真理, 呉 繁夫, 根東 義明

    日本腎臓学会誌　57　(3)　601-601　2015/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  23. 外科医と再生医学の最前線 損傷肝修復に貢献するヒト骨髄間葉系幹細胞中の特定の細胞、Muse細胞に関する研究

    片桐 弘勝, 西塚 哲, 串田 良祐, 久米 浩平, 遠藤 史隆, 石田 馨, 新田 浩幸, 高原 武志, 長谷川 康, 板橋 英教, 菅野 将司, 石橋 正久, 木村 祐輔, 大塚 幸喜, 肥田 圭介, 佐々木 章, 水野 大, 出澤 真理, 若林 剛

    日本外科学会雑誌　115　(臨増2)　218-218　2014/03

    Publisher: (一社)日本外科学会

    ISSN： 0301-4894

  24. Muse細胞研究の展望と課題

    若尾昌平, 串田良祐, 出沢真理

    最新医学　69　(3)　547-561　2014/03

    Publisher: (株)最新医学社

    ISSN： 0370-8241

  25. CD4+T細胞の増殖限界

    串田 良祐, 石田 隼也, 細野 正道

    臨床免疫・アレルギー科　58　(6)　706-714　2012/12

    Publisher: (有)科学評論社

    ISSN： 1881-1930

  26. ヘルパーT細胞 マウスCD4陽性効果T細胞の増殖限界 生体継代移入法による解析

    串田 良祐, 石田 隼也, 藤間 真紀, 細野 正道

    日本免疫学会総会・学術集会記録　40　33-33　2011/11

    Publisher: (NPO)日本免疫学会

    ISSN： 0919-1984

  27. 【胸腺におけるT細胞の分化とその機序】 胸腺の加齢による退縮の機序

    串田 良祐, 細野 正道

    臨床免疫・アレルギー科　56　(3)　269-275　2011/09

    Publisher: (有)科学評論社

    ISSN： 1881-1930

  28. 慢性DSS腸炎におけるトラニラストの治療効果のメカニズムに関する解析

    孫暁梅, 鈴木健司, 河内裕介, 山口花, 永田昌毅, 横山純二, 串田良祐, 細野正道, 渡辺賢一, 青柳豊, 安西光洋, 唐秀芳, 任旭

    消化器と免疫　(47)　90-95　2011

  29. 免疫と老化 マウスT細胞の機能増殖限界について 生体継代移入法による検討

    石田 隼也, 串田 良祐, 藤井 庄人, 藤間 真紀, 細野 正道

    基礎老化研究　34　(2)　35-35　2010/05

    Publisher: 日本基礎老化学会

    ISSN： 0912-8921

  30. 実験腸炎におけるトラニラストの治療効果のメカニズムに関する解析

    孫暁梅, 鈴木健司, 河内裕介, 横山純二, 串田良祐, 細野正道, 渡辺賢一, 永田昌毅, 青柳豊, 任旭

    消化器と免疫　(46)　175-179　2010/03

  31. 慢性DSS腸炎におけるplasmid-IL-10注腸治療効果の検討

    野々村頼子, 孫暁梅, 鈴木健司, 大坪亜矢, 遠藤悠, 河内裕介, 横山純二, 串田良祐, 大根田輝, 細野正道, 丸山弘樹, 渡辺賢一, 松田康伸, 永田昌毅, 青柳豊

    消化器と免疫　(46)　140-144　2010/03

  32. 実験的自己免疫性胃炎における自己抗体の意義-抗FcγR抗体投与による抑制効果-

    河内裕介, 斎藤翼, 孫暁梅, 鈴木健司, 串田良祐, 永淵正法, 細野正道, 青柳豊

    消化器と免疫　(45)　85-88　2009/03

    Publisher: 日本消化器免疫学会

  33. 慢性DSS腸炎におけるリザベン注腸治療効果の検討

    孫暁梅, 鈴木健司, 河内裕介, 横山純二, 斎藤翼, 熊谷さやか, 串田良祐, 大根田輝, 細野正道, 渡辺賢一, 松田康伸, 永田昌毅, 青柳豊

    消化器と免疫　(45)　139-143　2009/03

  34. DSS腸炎におけるplasmid-IL-10注腸治療効果の検討

    河合裕子, 孫暁梅, 鈴木健司, 河内裕介, 横山純二, 北澤侑恵, 斎藤翼, 大根田輝, 熊谷さやか, 串田良祐, 細野正道, 丸山弘樹, 渡辺賢一, 松田康伸, 永田昌毅, 青柳豊

    消化器と免疫　(45)　144-148　2009/03

  35. 加齢に伴う胸腺萎縮と末梢T細胞による副腎皮質網状帯の退縮

    串田 良祐, 熊谷 さやか, 藤井 庄人, 細野 正道

    基礎老化研究　32　(2)　50-50　2008/05

    Publisher: 日本基礎老化学会

    ISSN： 0912-8921

Show all ︎Show first 5

Presentations 70

  1. 劇症型心筋炎患者における内因性Muse細胞の心筋集積とその病態生理学的役割

    佐久間理吏, 豊田茂, 串田良祐, 相馬良一, 高山英士, 出沢真理, 井上晃男

    第24回日本再生医療学会　2025/03/21

  2. HUMAN POST-IMPLANTATION BLASTOCYST-LIKE CHARACTERISTICS OF NON-TUMORIGENIC MUSE CELLS ISOLATED FROM HUMAN UMBILICAL CORD

    Yoshihiro Kushida, Yo Oguma, Kana Abe, Taichi Deguchi, Federico Girolamo Barbera, Noriyuki Nishimura, Kazumichi Fujioka, Sota Iwatani, Mari Dezawa

    International Society for Stem Cell Research 2024　2024/07/12

  3. 量子科学的なアプローチで紐解く幹細胞・がん細胞・病的細胞の特性

    串田良祐, 出澤真理

    第6回量子生命科学会　2024/05/30

  4. ヒト臍帯由来Muse細胞とヒト初期胚との比較

    串田良祐、小熊陽、阿部香奈、出口敦智、 Federico Girolamo Barbera、西村範行、出澤真理

    第23回日本再生医療学会　2024/03/23

  5. Differentiation potential of Muse cells into trophoblast and primordial germ cell lineages beneficial for obstetrics and reproductive medicine

    2023/07/23

  6. Donor-Muse cell therapy for brain and spinal cord: free from surgical treatment, gene introduction, differentiation induction, HLA-matching and immunosuppressant.

    Mari Dezawa, Shohei Wakao, Yoshihiro Kushida, Kuniyasu Niizuma

    Gordon Research Conferences　2023/07

  7. Differentiation potential of umbilical cord-derived Muse cells into trophoblast and germ cell lineage

    The 79th Annual Meeting of The Japanese Society of Microscopy　2023/06/28

  8. Potential of Muse Cells as Endogenous Reparative Stem Cells Invited

    The 39th Annual Meeting of Japan Organization of Clinical Dermatologists　2023/06/17

  9. Kinetic analysis and therapeutic effect of Muse cells using bioluminescence imaging Invited

    Yoshihiro Kushida, Mari Dezawa

    日本顕微鏡学会 第78回学術講演会　2022/05/12

  10. オミックス解析による多能性幹細胞Muse細胞の性質を規定する因子の探索

    小熊 陽, 黒田 康勝, 若尾 昌平, 串田良祐, 出澤 真理

    第21回日本再生医療学会総会　2022/03

  11. 羊膜由来Muse細胞の発見と生殖細胞系列・胚体外組織への分化の可能性

    小川瑛史, 小熊陽, 大川香奈, 串田良祐, 若尾昌平, 出澤真理

    第21回日本再生医療学会総会　2022/03

  12. ヒトMuse細胞の栄養膜細胞・始原生殖細胞への分化の可能性 ~ナイーブ型多能性幹細胞の確立に向けて~

    大川香奈, 串田良祐, 若尾昌平, 黒田康勝, 松居靖久, 出澤真理

    第21回日本再生医療学会総会　2022/03

  13. Reprograming of Muse cells, endogenous pluripotent stem cells, toward totipotent-like property

    Kana Okawa, Yoshihiro Kushida, Shohei Wakao, Yasumasa Kuroda, Yasuhisa Matsui, Mari Dezawa

    第126回日本解剖学会総会・全国学術集会　2021/03

  14. ヒト羊膜およびマウス羊膜・胎盤由来のMuse細胞の単離および特性解析

    小川瑛史, 串田良祐, 若尾昌平, 大川香奈, 出澤真理

    第126回日本解剖学会総会・全国学術集会　2021/03

  15. 臍帯組織由来Muse細胞の栄養膜細胞への分化の可能性

    串田良祐, 若尾昌平, 西村範行, 岩谷壮太, 香田翼, 森岡一朗, 飯島一誠, 出澤真理

    第124回日本解剖学会　2019/03/29

  16. 臍帯組織由来Muse細胞の栄養膜細胞への分化

    串田良祐, 若尾昌平, 西村範行, 岩谷壮太, 香田翼, 森岡一朗, 飯島一誠, 出澤真理

    第18回日本再生医療学会　2019/03/21

  17. 修復幹細胞としてのMuse細胞の可能性 Invited

    串田良祐

    In vivoイメージングフォーラム2018　2018/10/19

  18. アフリカツメガエルの骨髄に由来する間葉系幹細胞の培養方法の確立

    大塚(山口)理奈, 黒田康勝, 串田良祐, 若尾昌平, 北田容章, 出澤真理

    第12回日本ツメガエル研究集会・第4回次世代両生類研究会 合同シンポジウム　2018/09

  19. 肝再生におけるMuse細胞移植の可能性

    伊関雅裕, 水間正道, 深瀬正彦, 小野智之, 志村充宏, 鈴木ゆき恵, 伊勢一郎, 石田晶玄, 工藤克昌, 林洋毅, 元井冬彦, 若尾昌平, 串田良祐, 亀井尚, 石田孝宣, 内藤剛, 出澤真理, 海野倫明

    第118回日本外科学会定期学術集会　2018/04/07

  20. Development of a novel antibody for pluripotent stem cell marker SSEA-3 International-presentation

    Yoshihiro KUSHIDA, Kazuki TATSUMI, Tatsuya SEGAWA, Mieko OHTSU, Noriyuki NISHIMURA, Masahiro MAEDA, Naoya MASUTOMI, Shohei WAKAO, Mari DEZAWA

    11th Pan Pacific Symposium on Stem Cells and Cancer Research　2018/03/24

  21. 臍帯組織由来Muse細胞の多能性の解析 －栄養膜細胞分化の可能性－

    串田良祐, 若尾昌平, 西村範行, 岩谷壮太, 香田翼, 森岡一朗, 溝渕雅巳, 飯島一誠, 出澤真理

    第17回日本再生医療学会　2018/03/22

  22. Multilineage-differentiating stress enduring cellsの低酸素性虚血性脳症モデルに対する治療効果の検討

    鈴木俊彦, 佐藤義朗, 清水忍, 串田良祐, 若尾昌平, 水野正明, 飛田秀樹, 出澤真理, 早川昌弘

    第17回日本再生医療学会　2018/03/21

  23. Multilineage-differentiating stress enduring cellsを用いた新生児慢性肺疾患に対する新規治療法の開発

    佐藤義朗, 鈴木俊彦, 清水忍, 串田良祐, 若尾昌平, 呉尚治, 北瀬悠磨, 見松はるか, 水野正明, 出澤真理, 早川昌弘

    第17回日本再生医療学会　2018/03/21

  24. 多能性幹細胞のマーカー糖鎖であるSSEA-3を認識する新規抗体の開発

    巽 一喜, 串田良祐, 瀬川辰也, 大津見枝子, 前田雅弘, 桝富直哉, 若尾昌平, 出澤真理

    第17回日本再生医療学会　2018/03/21

  25. ヒト末梢血中の多能性幹細胞Muse細胞の探索と機能解析

    佐藤哲哉, 若尾昌平, 串田良祐, 久志本成樹, 出澤真理

    日本解剖学会第63回東北・北海道連合支部学術集会　2017/09/10

  26. ラット肺虚血再灌流障害モデルにおけるMuse細胞の有効性

    矢吹皓, 若尾昌平, 串田良祐, 出澤真理, 岡田克典

    第53回日本移植学会　2017/08

  27. Differentiatian of Muse cells into Cardiomyocyte-like cells by Stepwise Cytokine Induction

    Mohamed Amin, Kushida Yoshihiro, Wakao Shohei, Tatsumi Kazuki, Dezawa Mari

    第122回日本解剖学会　2017/03/29

  28. 臍帯組織中に存在する非腫瘍性多能性幹細胞Muse細胞の機能解析

    串田良祐, 若尾昌平, 西村範行, 岩谷壮太, 香田翼, 森岡一朗, 溝渕雅巳, 飯島一誠, 出澤真理

    第122回日本解剖学会　2017/03/29

  29. Sphingosine-1-phosphate receptor 2 agonist mobilizes Muse cells to repair the heart damage

    湊口信吾, 山田好久, 若尾昌平, 串田良祐, 東賢志, 田中俊樹, 岩佐将充, 金森寛充, 川崎雅規, 西垣和彦, 出澤真理, 湊口信也

    第16回日本再生医療学会　2017/03/09

  30. ラット脳梗塞モデルに対する体性多能性幹細胞（Muse細胞）移植 ―機能改善と細胞動態の解析―

    森田隆弘, 内田浩喜, 新妻邦泰, 串田良祐, 若尾昌平, 松坂義哉, 坂田洋之, 虫明元, 出澤真理, 冨永悌二

    第16回日本再生医療学会　2017/03/09

  31. 肺虚血再灌流傷害モデルラットに対するMuse細胞による細胞治療

    矢吹皓, 若尾昌平, 串田良祐, 出澤真理, 岡田克典

    第16回日本再生医療学会　2017/03/09

  32. マウス肝障害モデルを用いたMuse細胞移植療法の検討

    伊関雅裕, 若尾昌平, 串田良祐, 水間正道, 元井冬彦, 海野倫明, 出澤真理

    第16回日本再生医療学会　2017/03/08

  33. O-43-3 Muse細胞投与はマウス急性膵炎モデルを改善する

    深瀬正彦, 坂田直昭, 若尾昌平, 串田良祐, 海野倫明, 出澤真理

    第16回日本再生医療学会　2017/03/08

  34. 組織損傷を伴う肝切除後のMuse(multilineage-differentiating stress-enduring)細胞による肝再生

    片桐弘勝, 鈴木悠地, 串田良祐, 久米浩平, 出澤真理, 西塚哲

    第16回日本再生医療学会　2017/03/08

  35. Muse細胞静脈内投与は血管構成細胞再生によりマウス大動脈瘤拡大を抑制する

    鷹谷紘樹, 細山勝寛, 若尾昌平, 串田良祐, 齋木佳克

    第16回日本再生医療学会　2017/03/08

  36. 免疫正常マウスを用いた慢性腎臓病モデルに対するMuse細胞治療の検討

    内田奈生, 串田良祐, 若尾昌平, 北田容章, 熊谷直憲, 呉繁夫, 出澤真理

    第16回日本再生医療学会　2017/03/07

  37. Differentiation of Muse cells into cardiomyocyte-like cells by stepwise cytokine induction

    Mohamed Amin, Kushida Yoshihiro, Wakao Shohei, Tatsumi Kazuki, Dezawa Mari

    第16回日本再生医療学会　2017/03/07

  38. 臍帯組織中に存在する非腫瘍性多能性幹細胞Muse細胞の機能解析

    串田良祐, 若尾昌平, 西村範行, 岩谷壮太, 香田翼, 森岡一朗, 溝渕雅巳, 飯島一誠, 出澤真理

    第16回日本再生医療学会　2017/03/07

  39. 臍帯組織中に存在する多能性幹細胞Muse細胞の自己複製能と多分化能の検証

    串田良祐, 若尾昌平, 明石英雄, 西村範行, 岩谷壮太, 香田翼, 森岡一朗, 溝渕雅巳, 飯島一誠, 出澤真理

    第121回日本解剖学会　2016/03/28

  40. 臍帯組織中に存在する多能性幹細胞Muse細胞の自己複製能と多分化能の検証

    串田良祐, 若尾昌平, 明石英雄, 西村範行, 岩谷壮太, 香田翼, 森岡一朗, 溝渕雅巳, 飯島一誠, 出澤真理

    第15回日本再生医療学会　2016/03/17

  41. 臍帯組織中に存在する多能性幹細胞Muse細胞の多能性の解析

    串田良祐, 若尾昌平, 明石英雄, 西村範行, 岩谷壮太, 香田翼, 森岡一朗, 溝渕雅巳, 飯島一誠, 出澤真理

    第42回日本臓器保存生物医学会学術集会　2015/11

  42. 臍帯組織中に存在する多能性幹細胞Muse細胞の多能性の解析

    串田良祐, 若尾昌平, 明石英雄, 西村範行, 岩谷壮太, 香田翼, 森岡一朗, 溝渕雅巳, 飯島一誠, 出澤真理

    日本解剖学会第61回東北・北海道連合支部学術集会　2015/08

  43. Analysis of pluripotency in Muse cells derived from human umbilical cord tissue. International-presentation

    Kushida Y, Wakao S, Akashi H, Nishimura N, Iwatani S, Koda T, Morioka I, Mizobuchi M, Iijima K, Dezawa M

    International Society for Stem Cell Research 2015 Annual Meeting　2015/06

  44. 慢性腎疾患モデルに対するMuse細胞を用いた細胞治療の検討

    内田奈生, 若尾昌平, 串田良祐, 熊谷直憲, 呉繁夫, 出澤真理

    第14回日本再生医療学会　2015/03

  45. マウス肝障害モデルを用いたMuse細胞移植療法の検討

    伊関雅裕, 若尾昌平, 串田良祐, 海野倫明, 出澤真理

    第14回日本再生医療学会　2015/03

  46. 臍帯組織由来の多能性幹細胞Muse細胞の探索と多能性の解析

    串田良祐, 若尾昌平, 明石英雄, 西村範行, 岩谷壮太, 香田翼, 森岡一朗, 溝渕雅巳, 飯島一誠, 出澤真理

    第14回日本再生医療学会　2015/03

  47. ウサギMuse細胞を用いた気管再生

    鈴木亮, 小椋文貴, 串田良祐, 若尾昌平, 仲江川雄太, 柳川明弘, 野本幸男, 大森孝一, 出澤真理

    日本解剖学会第60回東北・北海道連合支部学術集会　2014/09

  48. Muse細胞は慢性腎不全モデルにおいて糸球体構成細胞に分化し腎機能を改善する

    内田奈生, 串田良祐, 若尾昌平, 呉繁夫, 出澤真理

    日本解剖学会第60回東北・北海道連合支部学術集会　2014/09

  49. マウス肝障害モデルを用いたMuse細胞移植療法の検討

    伊関雅裕, 若尾昌平, 串田良祐, 海野倫明, 出澤真理

    日本解剖学会第60回東北・北海道連合支部学術集会　2014/09

  50. 臍帯組織由来の多能性幹細胞Muse細胞の探索と多能性の解析

    串田良祐, 若尾昌平, 明石英雄, 西村範行, 岩谷壮太, 香田翼, 森岡一朗, 溝渕雅巳, 飯島一誠, 出澤真理

    日本解剖学会第60回東北・北海道連合支部学術集会　2014/09

  51. 損傷肝修復に貢献するヒト骨髄間葉系幹細胞中の特定の細胞，Muse細胞に関する研究

    片桐弘勝, 西塚哲, 串田良祐, 久米浩平, 遠藤史隆, 石田馨, 新田浩幸, 高原武志, 長谷川康, 板橋英教, 菅野将司, 石橋正久, 木村祐輔, 大塚幸喜, 肥田圭介, 佐々木章, 水野大, 出澤真理, 若林剛

    第114回日本外科学会定期学術集会　2014/04

  52. 新生児線維芽細胞および臍帯血由来の多能性幹細胞Muse細胞の探索と機能解析

    串田良祐, 小椋文貴, 若尾昌平, 出澤真理

    第13回日本再生医療学会　2014/03

  53. 損傷肝修復に貢献するヒト骨髄間葉系幹細胞中の特定の細胞、Muse細胞に関する研究

    片桐弘勝, 西塚哲, 串田良祐, 久米浩平, 遠藤史隆, 石田馨, 佐藤慧, 新田浩幸, 高原武志, 長谷川康, 板橋英教, 菅野将司, 塩井義裕, 木村祐輔, 大塚幸喜, 肥田圭介, 佐々木章, 水野大, 出澤真理, 若林剛

    第20回外科侵襲とサイトカイン研究会　2013/12

  54. ラット脳梗塞モデルに対する新規多能性幹細胞の移植における細胞動態と機能回復の解析

    森田隆弘, 黒田康勝, 若尾昌平, 松坂義哉, 串田良祐, 内田浩喜, 遠藤俊毅, 冨永悌二, 出澤真理

    日本解剖学会第59回東北・北海道連合支部学術集会　2013/09

  55. 慢性腎障害モデルに対するMuse細胞の治療効果の検討

    内田奈生, 黒田康勝, 串田良祐, 若尾昌平, 呉繁夫, 出澤真理

    日本解剖学会第59回東北・北海道連合支部学術集会　2013/09

  56. ウサギMuse細胞を用いた気管再生

    鈴木亮, 小椋文貴, 串田良祐, 若尾昌平, 仲江川雄太, 柳川明弘, 野本幸男, 大森孝一, 出澤真理

    日本解剖学会第59回東北・北海道連合支部学術集会　2013/09

  57. 新生児由来の多能性幹細胞Muse細胞の探索と機能解析

    串田良祐, 小椋文貴, 若尾昌平, 出澤真理

    日本解剖学会第59回東北・北海道連合支部学術集会　2013/09

  58. Characterization and comparison of multilineage-differentiating stress enduring cells (Muse cells) from neonatal and adult fibroblasts. International-presentation

    Kushida Y, Ogura F, Wakao S, Dezawa M

    International Symposium Anatomical Science for advance in health and clinical therapy 2013　2013/08

  59. ヒト骨髄間葉系幹細胞由来Muse細胞による損傷肝修復に関する研究

    片桐弘勝, 西塚哲, 串田良祐, 滝川康裕, 出澤真理, 若林剛

    第9回広島肝臓プロジェクト研究センターシンポジウム　2013/06

  60. Intrinsic limitation of population size of murine CD4+ effector T cells in vivo

    KUSHIDA Yoshihiro

    2011

  61. マウスT細胞の増殖限界: 生体継代移入法による検討

    石田隼也, 串田良祐, 藤井庄人, 藤間真紀, 細野正道

    第82回日本動物学会　2011

  62. Age-related increase of a functional ratio of GC/DHEA mediated by peripheral T cells as a mechanism of the thymic involution with age. International-presentation

    Kushida Y, Touma M, Hosono M

    14th International Congress of Immunology　2010

  63. マウスT細胞の機能増殖限界について: 生体継代移入法による検討

    石田隼也, 串田良祐, 藤井庄人, 藤間真紀, 細野正道

    第33回日本基礎老化学会　2010

  64. 慢性DSS腸炎におけるトラニラストの治療効果のメカニズムに関する解析

    孫暁梅, 鈴木健司, 河内裕介, 山口花, 永田昌毅, 横山純二, 串田良祐, 細野正道, 渡辺賢一, 青柳豊, 安西光洋, 唐秀芳, 任旭

    日本消化器免疫学会　2010

  65. Age-related increase of a functional ratio of GC/DHEA in adrenal cortex mediated by peripheral T cells as a mechanism of the thymic involution with age

    2009

  66. DSS腸炎におけるplasmid-IL-10注腸治療効果の検討

    河合裕子, 孫暁梅, 鈴木健司, 河内裕介, 横山純二, 北澤侑恵, 斎藤翼, 大根田輝, 熊谷さやか, 串田良祐, 細野正道, 丸山弘樹, 渡辺賢一, 松田康伸, 永田昌毅, 青柳豊

    日本消化器免疫学会　2008

  67. 慢性DSS腸炎におけるリザベン注腸治療効果の検討

    孫暁梅, 鈴木健司, 河内裕介, 横山純二, 斎藤翼, 熊谷さやか, 串田良祐, 大根田輝, 細野正道, 渡辺賢一, 松田康伸, 永田昌毅, 青柳豊

    日本消化器免疫学会　2008

  68. 実験的自己免疫性胃炎における自己抗体の意義-抗FcγR抗体投与による抑制効果-

    河内裕介, 斎藤翼, 孫暁梅, 鈴木健司, 串田良祐, 永淵正法, 細野正道, 青柳豊

    日本消化器免疫学会　2008

  69. SAMP1マウスにおける新生仔期抗CD3抗体投与による胸腺肥大効果の減弱

    西村泰光, 串田良祐, 細川友秀, 細野正道

    第23回老化促進モデルマウス（SAM）研究協議会　2008

  70. 加齢に伴う胸腺萎縮と末梢T細胞による副腎皮質網状帯の退縮

    串田良祐, 熊谷さやか, 藤井庄人, 細野正道

    第31回日本基礎老化学会　2008

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Industrial Property Rights 2

  1. 運動ニューロン疾患（ＭＮＤ）の治療に有効な多能性幹細胞

    阿部康二, 山下徹, 出澤真理, 串田良祐, 岩瀬裕美子

    Property Type: Patent

  2. ハイポテンシャル多能性幹細胞

    出澤真理, 串田良祐

    Property Type: Patent

Research Projects 6

  1. 臍帯由来Muse細胞の全能性獲得への挑戦

    串田 良祐

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 東北大学

    2023/04 - 2027/03

  2. 急性心筋梗塞患者の末梢血で増加するMUSE細胞のプロファイル

    佐久間 理吏, 串田 良祐, 井上 晃男, 相馬 良一, 出沢 真理, 井上 健一

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 獨協医科大学

    2022/04 - 2025/03

  3. 臍帯由来Muse細胞の多能性制御機構の解明と胎盤機能不全に対する新規治療法の開発

    串田 良祐

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 東北大学

    2020/04/01 - 2023/03/31

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    Multilineage-differentiating Stress Enduring cell (Muse細胞)は生体組織に存在する腫瘍性を持たない多能性幹細胞である。一般的に多能性幹細胞はナイーブ型とプライム型に分類することができ、成体組織由来Muse細胞はプライム型の多能性幹細胞であると想定されているが、胎児付属物である臍帯は幼弱な組織であるため、臍帯由来Muse細胞は成体組織由来Muse細胞と比べ、より未分化なナイーブ型の幹細胞に近い状態であると考えられる。本研究では未解明である臍帯由来Muse細胞の多能性制御機構の解明を目的としている。 本年度は以下3項目を行った。 (1)ヒト臍帯由来Muse細胞の生殖細胞系列への分化誘導を試みたところ、臍帯由来Muse細胞ではBlimp1やNanos3などの始原生殖細胞マーカーの発現が認められ、生殖細胞系列への分化能を有する可能性が認められた。一方、骨髄由来Muse細胞ではこれらのマーカーの発現が認められないことから、ヒト臍帯由来Muse細胞がナイーブ型の幹細胞に近い性質を示すことが示唆された。 (2)RNA-seqにて骨髄、皮膚、脂肪、臍帯由来Muse細胞の遺伝子発現の差異を網羅的に解析したところ、臍帯由来Muse細胞で特異的に発現している因子を同定できた。この因子をshRNAにて発現を抑制したところ多能性因子の発現が低下したことから、臍帯由来Muse細胞の多能性を制御している可能性が示唆された。 (3) 骨髄、皮膚、脂肪、臍帯由来Muse細胞からゲノムDNAを回収し、Bisulfite処理した後、次世代シーケンサーを用いて網羅的にDNAメチル化の状態を解析した。

  4. Muse細胞を用いた急性心筋炎の病態解明および新規治療法確立

    井上 晃男, 串田 良祐, 相馬 良一, 出沢 真理, 正和 泰斗, 豊田 茂, 井上 健一

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 獨協医科大学

    2020/04/01 - 2023/03/31

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    基礎的研究：マウス心筋炎モデルを用いてMuse 細胞の治療効果を検証する予定であり、現在マウス心筋炎動物実験モデルの基礎的検証を行っている。今後マウス心筋炎モデルを用いてMuse細胞の治療効果を含めた検証を行う予定である。 臨床研究；劇症型急性心筋炎症例を対象に、経時的に末梢血を採取し遠心分離により単核球分画を分離しMuse細胞数を経時的に測定を行っている。Muse細胞はフローサイトメトリーを用いてSSEA-3陽性細胞として検出し同時にS1Pの動態観察を行っている。これまでに３例の劇症型心筋炎患者からMuse細胞数の経時的な検討を行っている。その結果入院初日に高値、その後低下した後に再度増加し７日目にピークを迎えその後低下する症例や、入院後５日目にピークを迎える症例等様々なパターンを呈している。これまでに我々が検討を行っている急性心筋梗塞とは当然のことながら明らかに違う動態を呈しており、今後更に症例数を重ねて劇症型急性心筋炎Muse細胞数の経時的な動態検討を行う予定である。また東北大学出澤、串田らの指導のもと、抽出されたMuse細胞についてMuse細胞機能に関与するOct3/4、Nanog、Sox2、Rex-1の4遺伝子の発現をリアルタイムPCR法により定量的に解析し、さらに増殖能(MTTアッセイ)、遊走能(マイグレーションアッセイ)、抗炎症作用(G-CSF産生: ELISA法)および抗アポトーシス能(TUNELアッセイ法)の評価を行い、通常のヒトMuse細胞と比較する予定である。

  5. 多能性幹細胞Muse細胞の遊走・分化制御機構の解明 Competitive

    串田 良祐

    Offer Organization: 文部科学省

    System: 若手研究（B）

    2017/04 - 2020/03

  6. 胎児付属物由来多能性幹細胞Muse細胞の特性解析と細胞移植治療を目指した基礎研究 Competitive

    串田 良祐

    Offer Organization: 文部科学省

    System: 若手研究（B）

    2014/04 - 2016/03

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Teaching Experience 2

  1. 肉眼解剖学　東北大学

  2. 組織学　東北大学