Xenografted human amniotic membrane-derived mesenchymal stem cells are immunologically tolerated and transdifferentiated into cardiomyocytes

Hiroko Tsuji, Shunichiro Miyoshi, Yukinori Ikegami, Naoko Hida, Hironori Asada, Ikuko Togashi, Junshi Suzuki, Masaki Satake, Hikaru Nakamizo, Mamoru Tanaka, Taisuke Mori, Kaoru Segawa, Nobuhiro Nishiyama, Junko Inoue, Hatsune Makino, Kenji Miyado, Satoshi Ogawa, Yasunori Yoshimura, Akihiro Umezawa

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Abstract

RATIONALE: Amniotic membrane is known to have the ability to transdifferentiate into multiple organs and is expected to stimulate a reduced immunologic reaction. OBJECTIVE: Determine whether human amniotic membrane-derived mesenchymal cells (hAMCs) can be an ideal allograftable stem cell source for cardiac regenerative medicine. METHODS AND RESULTS: We established hAMCs. After cardiomyogenic induction in vitro, hAMCs beat spontaneously, and the calculated cardiomyogenic transdifferentiation efficiency was 33%. Transplantation of hAMCs 2 weeks after myocardial infarction improved impaired left ventricular fractional shortening measured by echocardiogram (34±2% [n=8] to 39±2% [n=11]; P<0.05) and decreased myocardial fibrosis area (18±1% [n=9] to 13±1% [n=10]; P<0.05), significantly. Furthermore hAMCs transplanted into the infarcted myocardium of Wistar rats were transdifferentiated into cardiomyocytes in situ and survived for more than 4 weeks after the transplantation without using any immunosuppressant. Immunologic tolerance was caused by the hAMC-derived HLA-G expression, lack of MHC expression of hAMCs, and activation of FOXP3-positive regulatory T cells. Administration of IL-10 or progesterone, which is known to play an important role in feto-maternal tolerance during pregnancy, markedly increased HLA-G expression in hAMCs in vitro and, surprisingly, also increased cardiomyogenic transdifferentiation efficiency in vitro and in vivo. CONCLUSIONS: Because hAMCs have a high ability to transdifferentiate into cardiomyocytes and to acquire immunologic tolerance in vivo, they can be a promising cellular source for allograftable stem cells for cardiac regenerative medicine.

Original languageEnglish
Pages (from-to)1613-1623
Number of pages11
JournalCirculation research
Volume106
Issue number10
DOIs
Publication statusPublished - 2010 May 28

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Keywords

  • Cardiomyogenesis
  • Cell-based therapy
  • Human mesenchymal stem cell
  • Immunologic tolerance
  • Myocardial infarction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Tsuji, H., Miyoshi, S., Ikegami, Y., Hida, N., Asada, H., Togashi, I., Suzuki, J., Satake, M., Nakamizo, H., Tanaka, M., Mori, T., Segawa, K., Nishiyama, N., Inoue, J., Makino, H., Miyado, K., Ogawa, S., Yoshimura, Y., & Umezawa, A. (2010). Xenografted human amniotic membrane-derived mesenchymal stem cells are immunologically tolerated and transdifferentiated into cardiomyocytes. Circulation research, 106(10), 1613-1623. https://doi.org/10.1161/CIRCRESAHA.109.205260