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1 Cardiovascular Surgery, Toronto General Hospital, Toronto, Canada; Gynecology and Obstetrics, Harbin Medical University, Harbin, China
2 Cardiovascular Surgery, Toronto General Hospital, Toronto, Canada; Cardiovascular Surgery, Harbin Medical University, Harbin, China
3 Cardiovascular Surgery, Toronto General Hospital, Toronto, Canada
4 Surgery, Shiga University of Medical Science, Shiga, Japan
* To whom correspondence should be addressed. E-mail: renkeli{at}uhnres.utoronto.ca.
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. Methods: MCs were isolated from the adult rat uterus and cultured for three studies: (1) Intracellular VEGF levels were measured in MCs cultured with progesterone (10-11, 10-9 and 10-7M) (N=6 tests per group). (2) Blood vessel density was evaluated eight days after MCs (3x106 or 6x106), 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 (5x106/rat), or media were injected into a transmural scar three weeks after cryoinjury in rat hearts (N=12 rats per group), and heart function, blood vessel density, and myocardial scar size and thickness were evaluated five weeks later. Results: In study (1), cultured MCs expressed VEGF, with levels significantly (p<0.05) up-regulated by progesterone at an optimal dose of 10-11M. 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 (10-11M). 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.
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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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