Details of the Researcher

PHOTO

Yasumasa Kuroda
Section
Graduate School of Medicine
Job title
Assistant Professor
Degree
e-Rad No.
00614504

Research History 5

  • 2018/04 - Present
    Tohoku University Graduate School of Medicine　Department of Stem Cell Biology and Histology　Assistant Professor

  • 2013/05 - 2018/02
    Texas A&M College of Medicine　Institute for Regenerative Medicine　Postdoctoral Research Associate

  • 2012/04 - 2013/03
    Tohoku University Graduate School of Medicine　Department of Anatomy and Anthropology　Assistant Professor

  • 2011/04 - 2012/03
    Tohoku University Graduate School of Medicine　Department of Stem Cell Biology and Histology　Research Associate

  • 2008/10 - 2011/03
    Tohoku University

Education 2

  • 東北大学大学院　医学系研究科　博士課程

    2007/04 - 2011/03

  • Tokyo University of Science

    2005/04 - 2007/03

Professional Memberships 3

  • THE JAPANESE SOCIETY FOR REGENERATIVE MEDICINE

  • THE JAPANESE ASSOCIATION OF ANATOMISTS

  • THE JAPANESE SOCIETY OF MICROSCOPY

Research Interests 3

  • Regenerative Medicine

  • Stem Cells

  • Muse Cell

Research Areas 1

  • Life sciences / Anatomy /

Awards 7

  1. 特に優れた業績による大学院第一種奨学生返還免除 全額免除

    2011/03　独立行政法人 日本学生支援機構

  2. 東北大学総長賞

    2011/03　東北大学

  3. 東北医学会奨学賞

    2011/01　東北大学

  4. 東北大学大学院医学系研究科 辛酉優秀学生賞

    2010/10　東北大学

  5. 平成22年度奨学生

    2010/09　公益信託菅原医学振興基金

  6. 組織的な若手研究者等海外派遣プログラム 採用

    2010/06　日本学術振興会

  7. 平成21年度奨学生

    2009/09　公益信託菅原医学振興基金

Show all ︎Show 5

Papers 38

  1. Muse細胞静脈投与による長期間の脊髄虚血性障害治療効果

    大谷 将之, 串田 良祐, 黒田 康勝, 若尾 昌平, 阿部 香奈, 小熊 陽, 片平 晋太郎, 細山 勝寛, 出澤 真理, 齋木 佳克

    日本心臓血管外科学会雑誌　54　(4)　xv-xvii　2025/07

    Publisher: (NPO)日本心臓血管外科学会

    ISSN： 0285-1474

    eISSN： 1883-4108

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

    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 　

    More details Close

    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.

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

    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

    More details Close

    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.

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

    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 　

    More details Close

    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.

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

    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 　

    More details Close

    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.

  6. Inhibition of Gap Junctional Intercellular Communication Upregulates Pluripotency Gene Expression in Endogenous Pluripotent Muse Cells. International-journal

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

    Cells　11　(17)　2022/08/30

    DOI： 10.3390/cells11172701 　

    More details Close

    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.

  7. 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

  8. Effects of human Muse cells on bladder inflammation, overactivity, and nociception in a chemically induced Hunner-type interstitial cystitis-like rat model International-journal

    Akira Furuta, Yasumasa Kuroda, Tokunori Yamamoto, Shin Egawa, Mari Dezawa, Naoki Yoshimura

    International Urogynecology Journal　33　(5)　1293-1301　2022/03/25

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1007/s00192-022-05166-w 　

    ISSN： 0937-3462

    eISSN： 1433-3023

    More details Close

    INTRODUCTION AND HYPOTHESIS: We investigated the effects of locally administered human multilineage-differentiating stress enduring (Muse) cells, nontumorigenic pluripotent-like endogenous stem cells, on bladder tissues, function, and nociceptive behavior in a chemically induced Hunner-type interstitial cystitis (HIC)-like rat model without immunosuppressant. METHODS: Chemical cystitis was induced by intravesical instillation of 0.2 N hydrochloride (HCl) for 15 min in female F344 rats. SSEA-3+ Muse cells, SSEA-3- non-Muse cells or Hanks' balanced salt solution (HBSS; vehicle) were injected into the anterior and posterior bladder wall at each 1×104 cells/10 μl 6 h after HCl application. The sham group received HBSS without HCl instillation. Urinary frequency was assessed using metabolic cages, cystometrograms, nociceptive behavior, and histological analysis of the bladder and L6 spinal cord. RESULTS: Increases in urinary frequency and decreases in bladder capacity compared with the sham group were observed in the vehicle and non-Muse groups, but not in the Muse group, at 1 week. Significant increases in nociceptive behavior compared with the sham group and the expression of TNFα in the bladder and c-Fos in the bilateral dorsal horns of L6 spinal cord were also observed in the vehicle and non-Muse groups, whereas these changes were not seen in the Muse group at 1 week. Histological analysis exhibited a higher proportion of injected Muse cells remaining in the urothelial basal layer and lamina propria of the bladder than non-Muse cells until 4 weeks. CONCLUSIONS: Muse cell therapy could be a promising modality for treating HIC.

  9. Endogenous reparative pluripotent Muse cells with a unique immune privilege system: Hint at a new strategy for controlling acute and chronic inflammation. International-journal

    Yasumasa Kuroda, Yo Oguma, Kerrigan Hall, Mari Dezawa

    Frontiers in pharmacology　13　1027961-1027961　2022

    DOI： 10.3389/fphar.2022.1027961 　

    More details Close

    Multilineage-differentiating stress enduring (Muse) cells, non-tumorigenic endogenous pluripotent stem cells, reside in the bone marrow (BM), peripheral blood, and connective tissue as pluripotent surface marker SSEA-3(+) cells. They express other pluripotent markers, including Nanog, Oct3/4, and Sox2 at moderate levels, differentiate into triploblastic lineages, self-renew at a single cell level, and exhibit anti-inflammatory effects. Cultured mesenchymal stromal cells (MSCs) and fibroblasts contain several percent of SSEA-3(+)-Muse cells. Circulating Muse cells, either endogenous or administered exogenously, selectively accumulate at the damaged site by sensing sphingosine-1-phosphate (S1P), a key mediator of inflammation, produced by damaged cells and replace apoptotic and damaged cells by spontaneously differentiating into multiple cells types that comprise the tissue and repair the tissue. Thus, intravenous injection is the main route for Muse cell treatment, and surgical operation is not necessary. Furthermore, gene introduction or cytokine induction are not required for generating pluripotent or differentiated states prior to treatment. Notably, allogenic and xenogenic Muse cells escape host immune rejection after intravenous injection and survive in the tissue as functioning cells over 6 and ∼2 months, respectively, without immunosuppressant treatment. Since Muse cells survive in the host tissue for extended periods of time, therefore their anti-inflammatory, anti-fibrotic, and trophic effects are long-lasting. These unique characteristics have led to the administration of Muse cells via intravenous drip in clinical trials for stroke, acute myocardial infarction, epidermolysis bullosa, spinal cord injury, neonatal hypoxic ischemic encephalopathy, amyotrophic lateral sclerosis, and COVID-19 acute respiratory distress syndrome without HLA-matching or immunosuppressive treatment.

  10. 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

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

    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 　

    More details Close

    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.

  12. Protection of liver sinusoids by intravenous administration of human Muse cells in a rat extra‐small partial liver transplantation model

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

    American Journal of Transplantation　2021/01/15

    Publisher: Wiley

    DOI： 10.1111/ajt.16461 　

    ISSN： 1600-6135

    eISSN： 1600-6143

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

    Yamada Y, Wakao S, Kushida Y, Minatoguchi S, Mikami A, Higashi K, Baba S, Shigemoto T, Kuroda Y, Kanamori H, Amin M, Kawasaki M, Nishigaki K, Taoka M, Isobe T, Muramatsu C, Dezawa M, Minatoguchi S

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

    DOI： 10.1161/CIRCRESAHA.117.311648 　

    ISSN： 0009-7330

  14. Protocols for Isolation and Evaluation of Muse Cells. Peer-reviewed

    Tatsumi K, Kushida Y, Wakao S, Kuroda Y, Dezawa M

    Advances in experimental medicine and biology　1103　69-101　2018

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

    ISSN： 0065-2598

    eISSN： 2214-8019

  15. 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　2017/10

    DOI： 10.1681/ASN.2016070775 　

    ISSN： 1046-6673

    eISSN： 1533-3450

  16. iPS-derived MSCs from an expandable bank to deliver a prodrug-converting enzyme that limits growth and metastases of human breast cancers Peer-reviewed

    Ullah M, Kuroda Y, Bartosh T. J, Liu F, Zhao Q, Gregory C, Reger R, Xu J, Lee R. H, Prockop D. J

    CELL DEATH DISCOVERY　3　2017

    DOI： 10.1038/cddiscovery.2016.64 　

  17. iPS-derived MSCs from an expandable bank to deliver a prodrug-converting enzyme that limits growth and metastases of human breast cancers (vol 3, 16064, 2017) Peer-reviewed

    Ullah M, Kuroda Y, Bartosh T. J, Liu F, Zhao Q, Gregory C, Reger R, Xu J, Lee R. H, Prockop D. J

    CELL DEATH DISCOVERY　3　2017

    DOI： 10.1038/cddiscovery.2017.29 　

  18. 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

  19. 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　2016/01

    DOI： 10.1002/stem.2206 　

    ISSN： 1066-5099

    eISSN： 1549-4918

  20. Therapeutic Effects of Human Multilineage-Differentiating Stress Enduring (MUSE) Cell Transplantation into Infarct Brain of Mice Peer-reviewed

    Tomohiro Yamauchi, Yasumasa Kuroda, Takahiro Morita, Hideo Shichinohe, Kiyohiro Houkin, Mari Dezawa, Satoshi Kuroda

    PLOS ONE　10　(3)　e0116009　2015/03

    DOI： 10.1371/journal.pone.0116009 　

    ISSN： 1932-6203

  21. Unique multipotent cells in adult human mesenchymal cell populations (vol 107, pg 8639, 2014) Peer-reviewed

    Yasumasa Kuroda, Masaaki Kitada, Shohei Wakao, Kouki Nishikawa, Yukihiro Tanimura, Hideki Makinoshima, Makoto Goda, Hideo Akashi, Ayumu Inutsuka, Akira Niwa, Taeko Shigemoto, Yoko Nabeshima, Tatsutoshi Nakahata, Yo-ichi Nabeshima, Yoshinori Fujiyoshi, Mari Dezawa

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　111　(22)　8312-8312　2014/06

    DOI： 10.1073/pnas.1408449111 　

    ISSN： 0027-8424

  22. Human Adipose Tissue Possesses a Unique Population of Pluripotent Stem Cells with Nontumorigenic and Low Telomerase Activities: Potential Implications in Regenerative Medicine Peer-reviewed

    Fumitaka Ogura, Shohei Wakao, Yasumasa Kuroda, Kenichiro Tsuchiyama, Mozhdeh Bagheri, Saleh Heneidi, Gregorio Chazenbalk, Setsuya Aiba, Mari Dezawa

    STEM CELLS AND DEVELOPMENT　23　(7)　717-728　2014/04

    DOI： 10.1089/scd.2013.0473 　

    ISSN： 1547-3287

    eISSN： 1557-8534

  23. Mesenchymal Stem Cells and Their Subpopulation, Pluripotent Muse Cells, in Basic Research and Regenerative Medicine Peer-reviewed

    Yasumasa Kuroda, Mari Dezawa

    ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY　297　(1)　98-110　2014/01

    DOI： 10.1002/ar.22798 　

    ISSN： 1932-8486

    eISSN： 1932-8494

  24. A Novel Approach to Collecting Satellite Cells From Adult Skeletal Muscles on the Basis of Their Stress Tolerance Peer-reviewed

    Taeko Shigemoto, Yasumasa Kuroda, Shohei Wakao, Mari Dezawa

    STEM CELLS TRANSLATIONAL MEDICINE　2　(7)　488-498　2013/07

    DOI： 10.5966/sctm.2012-0130 　

    ISSN： 2157-6564

  25. Transplantation of bone marrow stromal cell-derived neural precursor cells ameliorates deficits in a rat model of complete spinal cord transection. International-journal Peer-reviewed

    Misaki Aizawa-Kohama, Toshiki Endo, Masaaki Kitada, Shohei Wakao, Akira Sumiyoshi, Dai Matsuse, Yasumasa Kuroda, Takahiro Morita, Jorge J Riera, Ryuta Kawashima, Teiji Tominaga, Mari Dezawa

    Cell transplantation　22　(9)　1613-25　2013

    DOI： 10.3727/096368912X658791 　

    ISSN： 0963-6897

  26. Autologous mesenchymal stem cell-derived dopaminergic neurons function in parkinsonian macaques Peer-reviewed

    Takuya Hayashi, Shohei Wakao, Masaaki Kitada, Takayuki Ose, Hiroshi Watabe, Yasumasa Kuroda, Kanae Mitsunaga, Dai Matsuse, Taeko Shigemoto, Akihito Ito, Hironobu Ikeda, Hidenao Fukuyama, Hirotaka Onoe, Yasuhiko Tabata, Mari Dezawa

    JOURNAL OF CLINICAL INVESTIGATION　123　(1)　272-284　2013/01

    DOI： 10.1172/JCI62516 　

    ISSN： 0021-9738

  27. Functional melanocytes are readily reprogrammable from multilineage- differentiating stress-enduring (muse) cells, distinct stem cells in human fibroblasts Peer-reviewed

    Kenichiro Tsuchiyama, Shohei Wakao, Yasumasa Kuroda, Fumitaka Ogura, Makoto Nojima, Natsue Sawaya, Kenshi Yamasaki, Setsuya Aiba, Mari Dezawa

    Journal of Investigative Dermatology　133　(10)　2425-2435　2013

    DOI： 10.1038/jid.2013.172 　

    ISSN： 1523-1747 0022-202X

  28. Isolation, culture and evaluation of multilineage-differentiating stress-enduring (Muse) cells Peer-reviewed

    Yasumasa Kuroda, Shohei Wakao, Masaaki Kitada, Toru Murakami, Makoto Nojima, Mari Dezawa

    Nature Protocols　8　(7)　1391-1415　2013

    DOI： 10.1038/nprot.2013.076 　

    ISSN： 1750-2799 1754-2189

  29. Morphologic and Gene Expression Criteria for Identifying Human Induced Pluripotent Stem Cells Peer-reviewed

    Shohei Wakao, Masaaki Kitada, Yasumasa Kuroda, Fumitaka Ogura, Toru Murakami, Akira Niwa, Mari Dezawa

    PLOS ONE　7　(12)　e48677　2012/12

    DOI： 10.1371/journal.pone.0048677 　

    ISSN： 1932-6203

  30. Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells. Peer-reviewed

    Wakao S, Kuroda Y, Ogura F, Shigemoto T, Dezawa M

    Cells　1　(4)　1045-1060　2012/11

    DOI： 10.3390/cells1041045 　

  31. Isolation of adult human pluripotent stem cells from mesenchymal cell populations and their application to liver damages Peer-reviewed

    Shohei Wakao, Masaaki Kitada, Yasumasa Kuroda, Mari Dezawa

    Methods in Molecular Biology　826　89-102　2012

    DOI： 10.1007/978-1-61779-468-1_8 　

    ISSN： 1064-3745

  32. 「身近な話題・世界の話題」(99)間葉系幹細胞における多様な分化と組織修復能を担うMuse細胞の発見

    黒田康勝, 出澤真理

    血液フロンティア　21　(11)　1664-1669　2011/10/30

    ISSN： 1344-6940

  33. Bone Marrow Mesenchymal Cells: How Do They Contribute to Tissue Repair and Are They Really Stem Cells? Peer-reviewed

    Yasumasa Kuroda, Masaaki Kitada, Shohei Wakao, Mari Dezawa

    ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS　59　(5)　369-378　2011/10

    DOI： 10.1007/s00005-011-0139-9 　

    ISSN： 0004-069X

  34. Multilineage-differentiating stress-enduring (Muse) cells are a primary source of induced pluripotent stem cells in human fibroblasts Peer-reviewed

    Shohei Wakao, Masaaki Kitada, Yasumasa Kuroda, Taeko Shigemoto, Dai Matsuse, Hideo Akashi, Yukihiro Tanimura, Kenichiro Tsuchiyama, Tomohiko Kikuchi, Makoto Goda, Tatsutoshi Nakahata, Yoshinori Fujiyoshi, Mari Dezawa

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　108　(24)　9875-9880　2011/06

    DOI： 10.1073/pnas.1100816108 　

    ISSN： 0027-8424

  35. 間葉系幹細胞の特性と再生医療における展開

    黒田康勝, 出澤真理

    再生医療　10　(1)　8-11　2011/02/01

    Publisher: (株)メディカルレビュー社

    ISSN： 1347-7919

  36. Lectins as a Tool for Detecting Neural Stem/Progenitor Cells in the Adult Mouse Brain Peer-reviewed

    Masaaki Kitada, Yasumasa Kuroda, Mari Dezawa

    ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY　294　(2)　305-321　2011/02

    DOI： 10.1002/ar.21311 　

    ISSN： 1932-8486

  37. Mesenchymal stem cells and umbilical cord as sources for schwann cell differentiation: Their potential in peripheral nerve repair

    Yasumasa Kuroda, Masaaki Kitada, Shohei Wakao, Mari Dezawa

    Open Tissue Engineering and Regenerative Medicine Journal　4　(1)　54-63　2011

    DOI： 10.2174/1875043501104010054 　

    ISSN： 1875-0435

  38. Unique multipotent cells in adult human mesenchymal cell populations Peer-reviewed

    Yasumasa Kuroda, Masaaki Kitada, Shohei Wakao, Kouki Nishikawa, Yukihiro Tanimura, Hideki Makinoshima, Makoto Goda, Hideo Akashi, Ayumu Inutsuka, Akira Niwa, Taeko Shigemoto, Yoko Nabeshima, Tatsutoshi Nakahata, Yo-ichi Nabeshima, Yoshinori Fujiyoshi, Mari Dezawa

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　107　(19)　8639-8643　2010/05

    DOI： 10.1073/pnas.0911647107 　

    ISSN： 0027-8424

Show all ︎Show first 5

Misc. 25

  1. マウス脊髄損傷モデルにおけるヒト骨髄由来Muse細胞の静脈投与効果発現メカニズムの解析

    熊谷玄太郎, 附田愛美, 長沖隼英, 猿田賢也, 佐々木勇, 和田簡一郎, 新戸部陽士郎, 油川広太郎, 串田良祐, 黒田康勝, 若尾昌平, 出澤真理, 石橋恭之

    弘前医学　75　(1)　2024

    ISSN： 0439-1721

  2. ヒト多能性幹細胞(Muse細胞)における新規多能性制御因子とその機能

    明石英雄, BAGHERI Mozhdeh, 若尾昌平, 黒田康勝, 柴田典人, 宮岸真, 北田容章, 藤吉好則, 田岡万悟, 磯辺俊明, 阿形清和, 出澤真理, 出澤真理

    再生医療　15　205　2016/02/01

    ISSN： 1347-7919

  3. ヒト成体多能性幹細胞にあける新規多能性制御因子の同定とその機能

    明石英雄, BAGHERI Mozhdeh, 若尾昌平, 黒田康勝, 柴田典人, 北田容章, 藤吉好則, 田岡万悟, 磯辺俊明, 阿形清和, 出澤真理, 出澤真理

    日本解剖学会総会・全国学術集会講演プログラム・抄録集　121st　130　2016

  4. プラナリアネオブラスト特異的抗体により同定された新規ヒト多能性制御因子とその機能

    明石英雄, BAGHERI Mozhdeh, 若尾昌平, 黒田康勝, 柴田典人, 北田容章, 藤吉好則, 田岡万悟, 磯辺俊明, 阿形清和, 出澤真理

    再生医療　14　282　2015/02/01

    ISSN： 1347-7919

  5. ヒトMuse細胞内に存在するサブポピュレーション

    若尾昌平, 黒田康勝, 出澤真理

    再生医療　14　281　2015/02/01

    ISSN： 1347-7919

  6. プラナリアネオブラスト特異的抗体によるヒト成体多能性幹細胞因子の同定

    明石英雄, MOZHDEH Bagheri, 若尾昌平, 黒田康勝, 柴田典人, 阿形清和, 田岡万悟, 礒辺俊明, 藤吉好則, 北田容章, 出澤真理

    再生医療　13　211　2014/01/27

    ISSN： 1347-7919

  7. ヒト生体由来多能性幹細胞(Muse細胞)内に存在するサブポピュレーションの解析

    若尾昌平, 黒田康勝, 出澤真理

    再生医療　13　211　2014/01/27

    ISSN： 1347-7919

  8. ヒトMuse細胞内に存在するサブポピュレーションの特性

    若尾昌平, 黒田康勝, 出澤真理

    日本解剖学会総会・全国学術集会講演プログラム・抄録集　119th　106　2014

  9. 他家移植へ向けたMuse細胞の可能性

    黒田康勝, 繁本妙子, 出澤真理

    日本解剖学会総会・全国学術集会講演プログラム・抄録集　118th　95　2013

  10. ヒト脂肪組織由来間葉系細胞に内在する多能性幹細胞の探索

    小椋文貴, 若尾昌平, 黒田康勝, 相場節也, 出澤真理

    日本解剖学会総会・全国学術集会講演プログラム・抄録集　118th　95　2013

  11. 多様なコロニーからヒトiPS細胞を選別するための形態的特徴と遺伝子発現

    若尾昌平, 北田容章, 黒田康勝, 小椋文貴, 村上徹, 丹羽明, 出澤真理

    日本解剖学会総会・全国学術集会講演プログラム・抄録集　118th　100　2013

  12. プラナリアネオブラスト特異的抗体により認識されるヒト多能性幹細胞因子の同定

    明石英雄, MOZHDEH Bagheri, 若尾昌平, 黒田康勝, 柴田典人, 阿形清和, 田岡万悟, 磯部俊明, 藤吉好則, 北田容章, 出澤真理

    日本解剖学会総会・全国学術集会講演プログラム・抄録集　118th　100　2013

  13. ヒト線維芽細胞に存在する多能性幹細胞(Muse細胞)とiPS細胞の関連性

    若尾 昌平, 北田 容章, 黒田 康勝, 出澤 真理

    日本生理学雑誌　75　(1)　34-35　2013/01/01

    Publisher: (一社)日本生理学会

    ISSN： 0031-9341

  14. プラナリア幹細胞特異的抗体を用いたヒト多能性幹細胞特異的因子の探索

    明石英雄, 若尾昌平, 黒田康勝, 柴田典人, 阿形清和, 田岡万悟, 磯辺俊明, 藤吉好則, 北田容章, 出澤真理

    再生医療　11　180　2012/05/16

    ISSN： 1347-7919

  15. 成人ヒト間葉系細胞に内在する多分化能細胞の探索

    黒田康勝, 北田容章, 若尾昌平, 西川幸希, 谷村幸宏, 合田真, 明石英雄, 繁本妙子, 藤吉好則, 出澤真理

    再生医療　11　180　2012/05/16

    ISSN： 1347-7919

  16. ヒト皮膚由来線維芽細胞に存在する多能性幹細胞とiPS細胞の関連

    若尾昌平, 北田容章, 黒田康勝, 繁本妙子, 明石英雄, 土山健一郎, 出澤真理

    解剖学雑誌　87　(1)　5-5　2012/03/01

    Publisher: (一社)日本解剖学会

    ISSN： 0022-7722

  17. 成体組織幹細胞の効率的な濃縮方法の確立:骨格筋を用いての検証

    繁本妙子, 黒田康勝, 若尾昌平, 北田容章, 出澤真理

    解剖学雑誌　87　(1)　4-4　2012/03/01

    Publisher: (一社)日本解剖学会

    ISSN： 0022-7722

  18. 成人ヒト間葉系細胞に内在する新規多能性幹細胞の探索

    黒田康勝, 北田容章, 若尾昌平, 谷村幸宏, 明石英雄, 繁本妙子, 出澤真理

    解剖学雑誌　87　(1)　5-5　2012/03/01

    Publisher: (一社)日本解剖学会

    ISSN： 0022-7722

  19. 成体組織幹細胞の効率的な単離方法の確立: 骨格筋を用いての検証

    繁本妙子, 黒田康勝, 若尾昌平, 北田容章, 出澤真理

    解剖学雑誌　86　(1)　10-10　2011/03

    Publisher: (一社)日本解剖学会

    DOI： 10.1007/s12565-010-0095-1 　

    ISSN： 0022-7722

  20. 皮膚由来線維芽細胞からのiPS細胞誘導における特定の幹細胞が寄与する可能性

    若尾昌平, 北田容章, 黒田康勝, 繁本妙子, 松瀬大, 明石英雄, 谷村幸宏, 出澤真理

    解剖学雑誌　86　(1)　10-10　2011/03

    Publisher: (一社)日本解剖学会

    DOI： 10.1007/s12565-010-0095-1 　

    ISSN： 0022-7722

  21. THE COMMENTARY 間葉系幹細胞の特性と再生医療における展開

    黒田 康勝, 出澤 真理

    再生医療　10　(1)　8-11　2011/02

    Publisher: メディカルレビュー社

    ISSN： 1347-7919

  22. 間葉系細胞に内在する多分化能細胞の探索

    黒田康勝, 北田容章, 若尾昌平, 出澤真理

    解剖学雑誌　85　(Supplement)　160-160　2010/03

    Publisher: (一社)日本解剖学会

    ISSN： 0022-7722

  23. 筋ジストロフィーに対する治療研究を臨床に展開するための統括的研究 III.筋再生と幹細胞移植治療 骨髄間葉系細胞からの有効な骨格筋誘導および筋変性モデルへの移植

    出澤真理, 若尾昌平, 繁本妙子, 北田容章, 黒田康勝, 松瀬大, 金丸眞一, 中村達雄, 武田伸一

    筋ジストロフィーに対する治療研究を臨床に展開するための統括的研究 平成19-21年度 総括研究報告書　60-63　2010

  24. 骨髄間葉系細胞の神経・骨格筋への分化転換におけるNotchの作用

    黒田康勝, 若尾昌平, 北田容章, 出澤真理

    解剖学雑誌　84　(Supplement)　253-253　2009/03

    Publisher: (一社)日本解剖学会

    ISSN： 0022-7722

  25. 進化工学的手法を用いたGAD65熱安定化変異体の獲得

    深沢健二, 榊大地, 渡辺秀吏, 黒田康勝, 上田哲也, 深沢寿太郎, 吉田充輝

    日本分子生物学会年会プログラム・講演要旨集　27th　886　2004/11/25

Show all ︎Show first 5

Research Projects 5

  1. リンパ節内における免疫寛容の獲得に向けたMuse細胞の分化の解明

    黒田 康勝

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2024/04/01 - 2027/03/31

  2. 生体内に存在する多能性幹細胞(Muse細胞)の免疫拒絶反応回避機構の解明

    黒田 康勝

    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

    More details Close

    本研究では、最終目標としてMuse細胞の免疫拒絶回避機構を明らかにし、さらに免疫抑制剤を使用しない臓器移植法の開発への足掛かりを得ることを目的としている。 昨年度は免疫抑制に重要な役割を果たすとされるヒト白血球抗原G (human leukocyte antigen-G, HLA-G)がMuse細胞に与える影響について解析するために、HLA-G promoterの下流にGFPを導入したMuse細胞し、分子的な側面から解析を進めると同時にin vivoにおいて特定の条件下ではMuse細胞が免疫系細胞とインタラクションしている可能性を示唆する結果を得ることに成功した。 今年度はこれらの知見を基として同種Muse細胞の投与によってレシピエントの免疫系細胞の体内分布にどのような変化が起こるのかを検討した。具体的にはBALB/cマウスに四塩化炭素を投与して肝臓傷害モデルを誘導した。翌日C57BL/6マウス由来Muse細胞を静脈投与し、時間経過とともに免疫系組織におけるTh細胞、B細胞、CTL, 骨髄由来抑制細胞(MDSC), 制御性T細胞(Treg)の増減をFACSで解析した。その結果、コントロールと比較しMuse細胞の投与がなされると、リンパ節ではB細胞以外の細胞が３日目には増加していた。また、傷害臓器である肝臓ではCTL, ヘルパーT細胞、B細胞、Tregが７日目以降に顕著に増加していた。注目すべき点として、免疫抑制に関わるMDSCがMuse細胞投与によって骨髄から動員され、末梢血を介して胸腺や脾臓に集積すること、Tregが３日では骨髄内で増加し、７日で脾臓や傷害肝臓に集積することがわかった。胸腺でのTreg はMuse細胞投与でむしろ減少の傾向があった。 今後、これらの現象が免疫拒絶回避にどのように関わるのか解析を進め、今後のMuse細胞の新たな応用の可能性について検証を進めていく。

  3. 生体内に存在する多能性幹細胞(Muse細胞)の分化メカニズムの経時的解析 Competitive

    黒田 康勝

    Offer Organization: 文部科学省

    System: 研究活動スタート支援

    2018/08 - 2020/03

  4. 新規多能性幹細胞 (Muse細胞) の起源探索および新規医療に向けた基礎解析 Competitive

    黒田 康勝

    Offer Organization: 文部科学省

    System: 若手研究（B）

    2013/04 - 2017/03

  5. 新規の多能性幹細胞Muse細胞の生体内における動態解析および発生学的起源の同定 Competitive

    黒田 康勝

    Offer Organization: 文部科学省

    System: 研究活動スタート支援

    2011/08 - 2012/03

Teaching Experience 1

  1. 組織学　東北大学