Cardiac stem cells differentiate into sinus node-like cells.
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.
Zhang
Jun
J
Department of Cardiology, Renmin Hospital and Cardiovascular Research Institute of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, People's Republic of China.
Huang
Congxin
C
Wu
Pan
P
Yang
Jing
J
Song
Tao
T
Chen
Yongjun
Y
Fan
Xinrong
X
Wang
Ten
T
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002469:Cell Separation; D002999:Clone Cells / Q000166:cytology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics; D004285:Dogs; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005434:Flow Cytometry; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D032386:Myoblasts, Cardiac / Q000166:cytology* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012849:Sinoatrial Node / Q000166:cytology* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology*
D015415:Biomarkers; D054815:Cyclic Nucleotide-Gated Cation Channels; D050991:GATA4 Transcription Factor; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D009124:Muscle Proteins; D019009:Proto-Oncogene Proteins c-kit