Cardiotrophic Growth Factor–Driven Induction of Human Muse Cells Into Cardiomyocyte-Like Phenotype

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

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


Multilineage-differentiating stress-enduring (Muse) cells are endogenous nontumorigenic stem cells collectable as stage-specific embryonic antigen 3 (SSEA-3) + from various organs including the bone marrow and are pluripotent-like. The potential of human bone marrow-derived Muse cells to commit to cardiac lineage cells was evaluated. We found that (1) initial treatment of Muse cells with 5′-azacytidine in suspension culture successfully accelerated demethylation of cardiac marker Nkx2.5 promoter; (2) then transferring the cells onto adherent culture and treatment with early cardiac differentiation factors including wingless-int (Wnt)-3a, bone morphogenetic proteins (BMP)-2/4, and transforming growth factor (TGF) β1; and (3) further treatment with late cardiac differentiation cytokines including cardiotrophin-1 converted Muse cells into cardiomyocyte-like cells that expressed α-actinin and troponin-I with a striation-like pattern. MLC2a expression in the final step suggested differentiation of the cells into an atrial subtype. MLC2v, a marker for a mature ventricular subtype, was expressed when cells were treated with Dickkopf-related protein 1 (DKK-1) and Noggin, inhibitors of Wnt3a and BMP-4, respectively, between steps (2) and (3). None of the steps included exogenous gene transfection, making induced cells feasible for future clinical application.

Original languageEnglish
Pages (from-to)285-298
Number of pages14
JournalCell Transplantation
Issue number2
Publication statusPublished - 2018 Feb 1


  • cardiomyocyte
  • cardiotrophin-1
  • nontumorigenic cells
  • pluripotency
  • suspension culture


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