title: A novel approach for myocardial regeneration with educated cord blood cells cocultured with cells from brown adipose tissue.
abstract: Umbilical cord blood (CB) is a promising source for regeneration therapy in humans. Recently, it was shown that CB was a source of mesenchymal stem cells as well as hematopoietic stem cells, and further that the mesenchymal stem cells could differentiate into a number of cells types of mesenchymal lineage, such as cardiomyocytes (CMs), osteocytes, chondrocytes, and fat cells. Previously, we reported that brown adipose tissue derived cells (BATDCs) differentiated into CMs and these CMs could adapt functionally to repair regions of myocardial infarction. In this study, we examined whether CB mononuclear cells (CBMNCs) could effectively differentiate into CMs by coculturing them with BATDCs and determined which population among CBMNCs differentiated into CMs. The results show that BATDCs effectively induced CBMNCs that were non-hematopoietic stem cells (HSCs) (educated CB cells: e-CBCs) into CMs in vitro. E-CBCs reconstituted infarcted myocardium more effectively than non-educated CBMNCs or CD34-positive HSCs. Moreover, we found that e-CBCs after 3 days coculturing with BATDCs induced the most effective regeneration for impaired CMs. This suggests that e-CBCs have a high potential to differentiate into CMs and that adequate timing of transplantation supports a high efficiency for CM regeneration. This strategy might be a promising therapy for human cardiac disease.
authors.affiliation: Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita-shi, 565-0871, Japan. yamaday@biken.osaka-u.ac.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kidoya
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Huang
authors.forename: Hisamichi
authors.initials: H
authors.lastname: Naitoh
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Satoh
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
mesh_terms: D017667:Adipocytes / Q000637:transplantation*; D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000637:transplantation*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods*; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D048091:Guided Tissue Regeneration / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology* / Q000601:surgery*; D051381:Rats; D011923:Rats, Nude; D016896:Treatment Outcome