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1Division of Cardiovascular Surgery and Toronto General Research Institute, Toronto General Hospital and University of Toronto, Toronto, Ontario, Canada; 2Department of Gynecology and Obstetrics, First Clinical College of Harbin Medical University; 3Division of Cardiovascular Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China; and 4Department of Surgery, Division of Cardiovascular Surgery, Shiga University of Medical Science, Shiga, Japan
Submitted 15 May 2006 ; accepted in final form 13 June 2006
Characteristically, uterine myometrial cells (MCs) are proliferative, inducing angiogenesis within the female reproductive organ. We evaluated whether MCs implanted into myocardium could also induce angiogenesis and restore heart function after injury. MCs were isolated from the adult rat uterus and cultured for three studies: 1) Intracellular VEGF levels were measured in MCs cultured with progesterone (1011, 109, and 107 M) (n = 6 tests per group). 2) Blood vessel density was evaluated 8 days after MCs (3 x 106 or 6 x 106), smooth muscle cells (SMCs), or endothelial cells (n = 6 rats per group) were injected with matrigel into the subcutaneous tissue of adult rats. 3) MCs, SMCs (5 x 106/rat), or media were injected into a transmural scar 3 wk after cryoinjury in rat hearts (n = 12 rats per group), and heart function, blood vessel density, and myocardial scar size and thickness were evaluated 5 wk later. In study 1, cultured MCs expressed VEGF, with levels significantly (P < 0.05) upregulated by progesterone at an optimal dose of 1011 M. In study 2, MCs injected into the subcutaneous tissue with matrigel induced significantly more blood vessels, especially large-diameter vessels, than did SMCs or endothelial cells (P < 0.01 for all groups). This angiogenic effect was greatest (P < 0.01) at higher doses of MCs and was enhanced by progesterone (1011 M). In study 3, MCs implanted into the injured myocardium increased blood vessel density at the implant area, reduced scar size, and improved cardiac function relative to SMCs and media. Overall, MCs induced angiogenesis in vitro and in vivo, prevented cardiac remodeling, and improved heart functional recovery after cardiac injury.
cell transplantation; heart failure; ischemic cardiomyopathy; angiogenic effect; heart function
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M. Boodhwani and F. W. Sellke Myometrium: another candidate for cell-based myocardial angiogenesis Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2039 - H2040. [Full Text] [PDF] |
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