Cardiac stem cells in brown adipose tissue express CD133 and induce bone marrow non-hematopoietic cells to differentiate into cardiomyocytes

¹ Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Department of Stem Cell Biology, Cancer Research Institute of Kanazawa University, Kanazawa, Japan; PREST, Japan Science and Technology Agency, Saitama, Japan
² Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan
³ Department of Stem Cell Biology, Cancer Research Institute of Kanazawa University, Kanazawa, Japan

^* To whom correspondence should be addressed. E-mail: ntakaku{at}biken.osaka-u.ac.jp.

	Abstract

Recently, there has been noteworthy progress in the field of cardiac regeneration therapy. We previously reported that brown adipose tissue (BAT) contained cardiac progenitor cells that were relevant to the regeneration of damaged myocardium. In this study, we found that CD133, not c-Kit or Sca-1, positive cells in BAT differentiated into cardiomyocytes (CMs) with a high frequency. Moreover, we found that CD133⁺BAT derived cells (BATDCs) effectively induced bone marrow cells (BMCs) into CMs. BMCs are considered to have the greatest potential as a source for CMs, and two sorts of stem cell populations, the mesenchymal (MSCs) and hematopoietic (HSCs) stem cells, have been reported to differentiate into CMs; however, it has not been determined which population is a better source for CMs. Here we show that CD133-positive BATDCs induce BMCs into CMs, not through cell fusion, but through bivalent cation mediated cell-to-cell contact when cocultured. Moreover, BMCs induced by BATDCs are able to act as CM repletion in an in vivo infarction model. Finally, we found that CD45^-CD31^-CD105⁺ non-hematopoietic cells, when cocultured with BATDCs, generated more than 20 times the number of CMs compared with lin^-c-Kit⁺ HSCs. Taken together, we suggest that CD133-positive BATDCs are a useful tool as CM inducers, as well as a source of CMs and that the non-hematopoietic fraction in BM is also a major source for CMs.

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