TY - JOUR
T1 - Stem cell therapy in the aging hearts of Fisher 344 rats
T2 - Synergistic effects on myogenesis and angiogenesis
AU - Min, Jiang Yong
AU - Chen, Yu
AU - Malek, Sohail
AU - Meissner, Achim
AU - Xiang, Meixiang
AU - Ke, Qinen
AU - Feng, Xin
AU - Nakayama, Masaharu
AU - Kaplan, Emel
AU - Morgan, James P.
N1 - Funding Information:
Supported in part by National Institutes of Health Grant R01 DA-12774 (Dr Morgan) and National Institute of Aging Grant 5P60 AG08814-13 (Dr Min). Dr Xiang (the 2nd affiliated Hospital, Medical College of Zhejiang University, China) is the recipient of a scholarship from the China Scholarship Council.
PY - 2005/8
Y1 - 2005/8
N2 - Objective: Advanced age is a major risk factor for ventricular dysfunction and reduction of cardiac reserve. Finding novel approaches to prevent and attenuate heart dysfunction associated with advanced age is a major therapeutic challenge. The present study was designed to test whether engrafted embryonic stem cells could improve myocardial function in aging hearts. Methods: Cultured mouse embryonic stem cells used for cell therapy were transfected with green fluorescent protein. Aging rats in the cell-treated group received intramyocardial injection of embryonic stem cells. Hemodynamic measurement, myocyte counting, and evaluation of blood flow were performed 6 weeks after cell transplantation. Results: Embryonic stem cell therapy partially improved cardiac reserve, as reflected by the in vivo response to isoproterenol (INN: isoprenaline) stimulation in aging hearts 6 weeks after cell implantation. The functional benefits from engrafted embryonic stem cells were associated with increased myocyte numbers and enhanced left ventricular blood perfusion in the aging heart. The characteristic phenotype of engrafted embryonic stem cells was identified in the transplanted heart on the basis of green fluorescent protein-positive spots that were further demonstrated to differentiate into cardiac tissue with positive staining for cardiac α-myosin heavy chain. Conclusions: Regenerating cardiomyocytes and increasing regional blood perfusion in the aging heart after embryonic stem cell transplantation synergistically resulted in improvement of cardiac function. Embryonic stem cell transplantation might hold significant clinical potential in attenuating the progressive decrease of cardiac function associated with advanced aging.
AB - Objective: Advanced age is a major risk factor for ventricular dysfunction and reduction of cardiac reserve. Finding novel approaches to prevent and attenuate heart dysfunction associated with advanced age is a major therapeutic challenge. The present study was designed to test whether engrafted embryonic stem cells could improve myocardial function in aging hearts. Methods: Cultured mouse embryonic stem cells used for cell therapy were transfected with green fluorescent protein. Aging rats in the cell-treated group received intramyocardial injection of embryonic stem cells. Hemodynamic measurement, myocyte counting, and evaluation of blood flow were performed 6 weeks after cell transplantation. Results: Embryonic stem cell therapy partially improved cardiac reserve, as reflected by the in vivo response to isoproterenol (INN: isoprenaline) stimulation in aging hearts 6 weeks after cell implantation. The functional benefits from engrafted embryonic stem cells were associated with increased myocyte numbers and enhanced left ventricular blood perfusion in the aging heart. The characteristic phenotype of engrafted embryonic stem cells was identified in the transplanted heart on the basis of green fluorescent protein-positive spots that were further demonstrated to differentiate into cardiac tissue with positive staining for cardiac α-myosin heavy chain. Conclusions: Regenerating cardiomyocytes and increasing regional blood perfusion in the aging heart after embryonic stem cell transplantation synergistically resulted in improvement of cardiac function. Embryonic stem cell transplantation might hold significant clinical potential in attenuating the progressive decrease of cardiac function associated with advanced aging.
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U2 - 10.1016/j.jtcvs.2005.03.017
DO - 10.1016/j.jtcvs.2005.03.017
M3 - Article
C2 - 16077426
AN - SCOPUS:23044439145
SN - 0022-5223
VL - 130
SP - 547
EP - 553
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 2
ER -