Bone Marrow-derived Side Population Cells are Capable of Functional Cardiomyogenic Differentiation

  • Yoon, Jihyun (Department of Cardiology, College of Medicine, Korea University) ;
  • Choi, Seung-Cheol (Department of Cardiology, College of Medicine, Korea University) ;
  • Park, Chi-Yeon (Department of Cardiology, College of Medicine, Korea University) ;
  • Choi, Ji-Hyun (Department of Cardiology, College of Medicine, Korea University) ;
  • Kim, Yang-In (Department of Physiology and Neuroscience Research Institute, College of Medicine, Korea University) ;
  • Shim, Wan-Joo (Department of Cardiology, College of Medicine, Korea University) ;
  • Lim, Do-Sun (Department of Cardiology, College of Medicine, Korea University)
  • Received : 2007.07.13
  • Accepted : 2007.12.13
  • Published : 2008.04.30

Abstract

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 $19.59%{\pm}9.00\;CD14^+$, $8.22%{\pm}2.72\;CD34^+$, $92.93%{\pm}2.68\;CD44^+$, $91.86%{\pm}4.07\;CD45^+$, $28.48%{\pm}2.24\;c-kit^+$, $71.09%{\pm}3.67\;Sca-1^+$. 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, $7.2%{\pm}1.2$ 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.

Keywords

Bone Marrow;Cardiomyogenic Differentiation;Side Population Cells

Acknowledgement

Supported by : Ministry of Science and Technology

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