Bone marrow-derived side population cells are capable of functional cardiomyogenic differentiation.
It has been reported that bone marrow (BM)-side population (SP) cells, with hematopoietic stem cell activity, can transdifferentiate into cardiomyocytes and contribute to myocardial repair. However, this has been questioned by recent studies showing that hematopoietic stem cells (HSCs) adopt a hematopoietic cell lineage in the ischemic myocardium. The present study was designed to investigate whether BM-SP cells can in fact transdifferentiate into functional cardiomyocytes. Phenotypically, BM-SP cells were 19.59% (+/-)9.00 CD14+, 8.22% (+/-)2.72 CD34+, 92.93% (+/-)2.68 CD44+, 91.86% (+/-)4.07 CD45+, 28.48% (+/-)2.24 c-kit+, 71.09% (+/-)3.67 Sca-1+. Expression of endothelial cell markers (CD31, Flk-1, Tie-2 and VEGF-A) was higher in BM-SP cells than whole BM cells. After five days of co-culture with neonatal cardiomyocytes, 7.2% (+/-)1.2 of the BM-SP cells expressed sarcomeric alpha-actinin as measured by flow cytometry. Moreover, BM-SP cells co-cultured on neonatal cardiomyocytes fixed to inhibit cell fusion also expressed sarcomeric alpha-actinin. The co-cultured BM-SP cells showed neonatal cardiomyocyte-like action potentials of relatively long duration and shallow resting membrane potential. They also generated calcium transients with amplitude and duration similar to those of neonatal cardiomyocytes. These results show that BM-SP cells are capable of functional cardiomyogenic differentiation when co-cultured with neonatal cardiomyocytes.
Yoon
Jihyun
J
Department of Cardiology, College of Medicine, Korea University, Seoul 136-705, Korea.
Choi
Seung-Cheol
SC
Park
Chi-Yeon
CY
Choi
Ji-Hyun
JH
Kim
Yang-In
YI
Shim
Wan-Joo
WJ
Lim
Do-Sun
DS
D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D020013:Calcium Signaling; D002454:Cell Differentiation; D002459:Cell Fusion; D002469:Cell Separation; D054338:Cell Transdifferentiation; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D032383:Myocytes, Cardiac / Q000166:cytology*
D015415:Biomarkers