| 윤지현, 안혜진, 최승철, 신성희, 박미영, 김영훈, 심완주, 노영무, 임도선 |
Background : There have been known that bone marrow-derived cells have been suggested to regenerate cardiomyocytes through transdifferentiation in myocardial infarcts. However, there are still debates whether engrafted bone marrow-derived cells can transdifferentiate into cardiomyocytes or not. Here, we demonstrate cardiac differentiation of bone marrow derived hematopoietic stem cells under in vitro and in vivo assays. Method and Results : Single-cell suspensions of bone marrow of C57BL/6 (6 to 12-wk-old) mice were isolated with Hoechst 33342 dye, called side population cells, and analyzed for hematopoietic cell surface marker expression. The phenotype characteristics and differentiation potential of enriched cells were analyzed by immunocytochemical, real time-PCR, and electrophysiological analyses. Side population(SP) cells existed at a frequency of 0.03 % to 0.1% in the bone marrow cell suspension. The vast majority of SP (n = 5) showed primitive cell phenotype such as Sca-1+, c-kit+, and CD45+ (71.6 ± 11.1 %, 27.7 ± 3.9 %, and 96.7 ± 1.1 %, respectively). DiI-labeled SP cells underwent cardiomyogenic specification after co-culture with beating neonatal cardiomyocytes(1-day old). We found some beating SP cells 6 days after coculture. They also expressed sarcomeric-α-actinin as a cardiac marker and were displayed similar electrophysiologic action potentials with neonatal cardiomyocytes based on current-voltage profiles, suggesting their potential of functional activity of cardiomyocytes. DiI-labeled SP cells were directly injected into infarcted myocardium and harvested the heart after 2 weeks. DiI-labeled SP cells were engrafted in infarcted myocardium and expressed sarcomeric-α-actinin and cardiac myosin heavy chain. Echocardiography showed that DiI-labeled SP cell group had better (p<0.05) left ventricular performance than control group. Discussion: The present data demonstrates that bone marrow derived hematopoietic cells can differentiate into beating cardiomyocytes and eventually improve heart function after SP transplantation.
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