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TISSUE-SPECIFIC STEM CELLS |
1 Cardio-pulmonary division of Keio University School of Medicine, Tokyo, JAPAN
2 Cardio-pulmonary division of Keio University School of Medicine, Tokyo, JAPAN; Keio University School of Medicine Institute for Advanced Cardiac Therapeutics, Tokyo, JAPAN
3 Cardio-pulmonary division of Keio University School of Medicine, Tokyo, JAPAN; Department of Reproductive Biology and Pathology, National Research Institute for Child Health and Development, Tokyo, JAPAN
4 Department of Reproductive Biology and Pathology, National Research Institute for Child Health and Development, Tokyo, JAPAN
5 Department of Surgery, Keio University School of Medicine, Tokyo, JAPAN
6 Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, JAPAN
7 Department of Pathology, Keio University School of Medicine, Tokyo, JAPAN
* To whom correspondence should be addressed. E-mail: smiyoshi{at}cpnet.med.keio.ac.jp.
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Abstract |
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We tested the cardiomyogenic (CM) potential of the human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs). Both the number and function of stem cells may be depressed in senile patients with severe coronary risk factors. Therefore, stem cells obtained from such patients may not function well. For this reason, UCBMSCs are potentially a new cell source for stem cell-based therapy, since such cells can be obtained from younger populations and are being routinely utilized for clinical patients.
Methods and Results: The human UCBMSCs (5x103/cm2) were co-cultured with fetal murine cardiomyocytes (CM:1x105/cm2). On day 5 of co-cultivation, about half of the GFP-labeled UCBMSCs contracted rhythmically and synchronously, suggesting the presence of electrical communication between the UCBMSCs. The fractional shortening of the contracted UCBMSCs was 6.5 ± 0.7 % (n=20). The UCBMSC-derived cardiomyocytes stained positive for cardiac troponin-I (clear striation +) and connexin 43 (diffuse dot-like staining at the margin of the cell) by the immunocytochemical method. Cardiac troponin-I positive cardiomyocytes accounted for 45 ± 3 % of GFP-labeled UCBMSCs. The cardiomyocyte-specific long action potential duration (186 ± 12 msec) was recorded with a glass microelectrode from the GFP-labeled UCBMSCs. CM was observed in UCBMSCs, which were co-cultivated in the same dish with mouse cardiomyocytes separated by a collagen membrane. Cell fusion, therefore, was not a major cause of CM in the UCBMSCs.
Conclusions: About half of the human UCBMSCs were successfully transdifferentiated into cardiomyocytes in vitro. UCBMSCs can be a promising cellular source for cardiac stem cell-based therapy.
Key Words. Physiology, Transplantation, Action potentials, Cells, Heart failure
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