Basic Medicine, Molecular and Cellular Biology

Stem Cell Biology and Histology

Challenge to Pioneering Next-Generation Regenerative Medicine Based on Non-Tumorigenic Endogenous Pluripotent Muse Cells

Medical Sciences Course

  • Master / Doctoral Degree



Professor, M.D. Ph.D.

*Concurrent Position

Research Theme

  • Evaluation of Muse cell efficiency and safety in disease models
  • In vivo dynamics and reparative functions of Muse cells
  • Development and evolution of Muse cells
Research Keywords:

regenerative medicine, pluripotent stem cells, reparative medicine, Stem cell differentiation, stem cells

Technical Keywords:

cell culture, gene expression analysis, cell kinetics, animal experiment, histological analysis

Laboratory Introduction

We discovered a novel type of endogenous pluripotent stem cells termed "Multilineage-differentiating stress-enduring (Muse)" cells. They were first identified in the bone marrow, dermis and adipose tissue, but recent progress clarified their presence in the peripheral blood and connective tissue of every organ. They are also obtainable from cultured fibroblasts and bone marrow-mesenchymal stem cells. For easy accessibility and non-tumorigenicity, Life Science Institute Inc., a group company of Mitsubishi Chemical Holdings Company, is currently propelling Muse cell project (see Nature Outlook; Since they are pluripotent, they can generate endodermal-, mesodermal and ectodermal-lineage cells from single cell and self-renew. The most prominent feature of Muse cells that is not recognized in other pluripotent stem cells is that they can home into damage tissue only by intravenous injection and spontaneously differentiate into tissue-compatible cells to repair tissue. For this, regenerative medicine with intravenous drip, one of the most expedient procedure, is expected to be actualized. Our team is currently focusing on several subjects in collaboration with domestic and international research groups; 1) in vivo dynamics of Muse cells in normal and diseased conditions, 2) the mechanism of spontaneous differentiation of Muse cells into tissue-compatible cells after integration, 3) developmental origin of Muse cells and 4) evaluation of efficiency and safety in disease models.

Figure 1. Strategy of Muse cell treatment

Figure 1. Strategy of Muse cell treatment

Recent Publications

  • Kuroda Y, et al. Unique multipotent cells in adult human mesenchymal cell populations. Proc Natl Acad Sci U S A, 107: 8639-8643, 2010.
  • Wakao S, et al. Multilineage-differentiating stress-enduring (Muse) cells are a primary source of induced pluripotent stem cells in human fibroblasts. Proc Natl Acad Sci U S A, 108: 9875-9880, 2011.
  • Kuroda Y, et al. Isolation, culture and evaluation of multilineage-differentiating stress-enduring (Muse) cells. Nat Protoc, 8: 1391-1415, 2013.
  • Uchida N, et al. Beneficial Effects of Systemically Administered Human Muse Cells in Adriamycin Nephropathy. J Am Soc Nephrol, 28(10):2946-2960, 2017.
  • Yamada Y, et al. S1P-S1PR2 Axis Mediates Homing of Muse Cells Into Damaged Heart for Long-Lasting Tissue Repair and Functional Recovery After Acute Myocardial Infarction. Circ Res, 122(8):1069-1083, 2018.