Cardiac Stem Cells Differentiate into Sinus Node-Like Cells

Cardiac Stem Cells Differentiate into Sinus Node-Like Cells

JUN ZHANG,¹ CONGXIN HUANG,¹ PAN WU,¹ JING YANG,¹ TAO SONG,¹ YONGJUN CHEN,¹ XINRONG FAN¹ and TEN WANG¹

¹Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Cardiovascular Research Institute, Wuhan University, Wuhan, PR China

The advent of stem cell therapy brings about the hope to restore the loss of cardiac pacemaker cells. However, it is largely unknown whether cardiac stem cells are able to differentiate into pacemaker cells. The purpose of this study was to determine whether the heart of large juvenile mammals contains cardiac stem cells (CSCs), which are suitable as seed cells for restoration of cardiac pacemaker cell. The c-kit⁺ CSCs were isolated from one-month-old mongrel dogs. CSCs that we sorted were self-renewing, and they could proliferate by clonal expansion. CSCs could differentiate into cardiac muscle, smooth muscle and endothelial cells at rates of 10.5 ± 4.2%, 13.5 ± 5.1% and 12.9 ± 3.5%, respectively, at week 4, as judged by the expression of respective differentiation markers: cardiac troponin I, smooth muscle actin, and CD31. At week 8, the differentiation rates were further increased to 23.2 ± 3.6%, 25.9 ± 6.6% and 28.3 ± 6.1% (P < 0.05 for each marker). Some of cells derived from CSCs could express cardiac transcription factor GATA-4 after week 2 and express pacing-related genes, including hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) and HCN4 after week 4. Importantly, a fraction of CSCs demonstrated the presence of inward currents that indicate the expression of inward current channels. In conclusion, c-kit⁺ CSCs may differentiate into cardiac muscle cell and sinus node-like cells, suggesting that CSCs would be useful as seed cells in treating sinus bradycardiac disorders or exploring the mechanism of pacemaker activity.

keywords —— cardiac stem cell; expansion; differentiation; c-kit; dog

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Tohoku J. Exp. Med., 2010, 222, 113-120

Correspondence: Congxin Huang, M.D., Department of Cardiology, Renmin Hospital of Wuhan University and Cardiovascular Research Institute of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, 430060, People's Republic of China.

e-mail: huangcongxing@yahoo.com.cn