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TISSUE-SPECIFIC STEM CELLS |
aCardiopulmonary Division, Keio University School of Medicine, Tokyo, Japan;
bKeio University School of Medicine, Institute for Advanced Cardiac Therapeutics, Tokyo, Japan;
cDepartment of Reproductive Biology and Pathology, National Research Institute for Child Health and Development, Tokyo, Japan;
dDepartment of Surgery,
eDepartment of Pathology, and
fDepartment of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan
Key Words. Physiology • Transplantation • Action potentials • Cells • Heart failure
Correspondence: Shunichiro Miyoshi, M.D., Ph.D., Cardiopulmonary Division of Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan. Telephone: +81-3-3353-1211 (ext. 62310); Fax: +81-3-3353-2502; e-mail: smiyoshi{at}cpnet.med.keio.ac.jp
Received October 23, 2006;
accepted for publication May 6, 2007.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS May 10, 2007.
We tested the cardiomyogenic 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. The human UCBMSCs (5 x 103 per cm2) were cocultured with fetal murine cardiomyocytes ([CM] 1 x 105 per cm2). On day 5 of cocultivation, approximately half of the green fluorescent protein (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 milliseconds) was recorded with a glass microelectrode from the GFP-labeled UCBMSCs. CM were observed in UCBMSCs, which were cocultivated 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. Approximately 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.
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