title: Cardiac stem cells in brown adipose tissue express CD133 and induce bone marrow nonhematopoietic cells to differentiate into cardiomyocytes.
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-positive, but not c-Kit- or Sca-1-positive, cells in BAT differentiated into cardiomyocytes (CMs) with a high frequency. Moreover, we found that CD133(+) brown adipose tissue-derived cells (BATDCs) effectively induced bone marrow cells (BMCs) into CMs. BMCs are considered to have the greatest potential as a source of CMs, and two sorts of stem cell populations, the MSCs and hematopoietic stem cells (HSCs), have been reported to differentiate into CMs; however, it has not been determined which population is a better source of 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(+) nonhematopoietic cells, when cocultured with BATDCs, generated more than 20 times the number of CMs compared with lin(-)c-Kit(+) HSCs. Taken together, these data suggest that CD133-positive BATDCs are a useful tool as CM inducers, as well as a source of CMs, and that the nonhematopoietic fraction in bone marrow is also a major source of CMs. Disclosure of potential conflicts of interest is found at the end of this article.
authors.affiliation: Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita-shi, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Xiang-Di
authors.initials: XD
authors.lastname: Wang
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
mesh_terms: D000071916:AC133 Antigen; D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002413:Cations, Divalent / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002459:Cell Fusion; D018920:Coculture Techniques; D006023:Glycoproteins / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects; D010455:Peptides / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D002413:Cations, Divalent; D006023:Glycoproteins; D010455:Peptides; C000606024:Prom1 protein, mouse; C000606025:Prom1 protein, rat