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Engineered early embryonic cardiac tissue retains proliferative and contractile properties of developing embryonic myocardium

¹Cardiovascular Development Research Program, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, and Department of Pediatrics, University of Pittsburgh School of Medicine; and Departments of ²Bioengineering and of ³Physiology and Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Submitted 27 February 2006 ; accepted in final form 6 April 2006

Embryonic myocardium has a high rate of cell proliferation and regulates cellular proliferation, contractile function, and myocardial architecture in response to changes in external mechanical loads. However, the small and complex three-dimensional (3D) structure of the embryonic myocardium limits our ability to directly investigate detailed relationships between mechanical load, contractile function, and cardiomyocyte proliferation. We developed a novel 3D engineered early embryonic cardiac tissue (EEECT) from early embryonic ventricular cells to test the hypothesis that EEECT retains the proliferative and contractile properties of embryonic myocardium. We combined freshly isolated White Leghorn chicken embryonic ventricular cells at Hamburger-Hamilton (HH) stage 31 (day 7 of a 46-stage, 21-day incubation period), collagen type I, and matrix factors to construct cylindrical-shaped EEECTs. We studied tissue architecture, cell proliferation patterns, and contractile function. We then generated engineered fetal cardiac tissue (EFCT) from HH stage 40 (day 14) fetal ventricular cells for direct comparison with EEECT. Tissue architecture was similar in EEECT and EFCT. EEECT maintained high cell proliferation patterns by culture day 12, whereas EFCT decreased cell proliferation rate by culture day 9 (P < 0.05). EEECT increased active contractile force from culture day 7 to day 12. The culture day 12 EEECT contractile response to the -adrenergic stimulation was less than culture day 9 EFCT (P < 0.05). Cyclic mechanical stretch stimulation induced myocardial hyperplasia in EEECT. Results indicate that EEECT retains the proliferative and contractile properties of developing embryonic myocardium and shows potential as a robust in vitro model of developing embryonic myocardium.

cardiomyocyte; morphogenesis; growth and development; hyperplasia; tissue engineering

This article has been cited by other articles:

				B. B. KELLER, L. J. LIU, J. P. TINNEY, and K. TOBITA Cardiovascular Developmental Insights from Embryos Ann. N.Y. Acad. Sci., April 1, 2007; 1101(1): 377 - 388. [Abstract] [Full Text] [PDF]