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Growth of EngineeredHuman Myocardium WithMechanical Loadingand VascularCoculture Nathaniel L. TullochVeronica MuskheliMaria V. Razumova2011 год

Growth of Engineered Human Myocardium With Mechanical Loading and Vascular Coculture
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Аннотация: Rationale: The developing heart requires both mechanical load and vascularization to reach its proper size, yet the regulation of human heart growth by these processes is poorly understood. Objective: We seek to elucidate the responses of immature human myocardium to mechanical load and vascularization using tissue engineering approaches. Methods and Results: Using human embryonic stem cell and human induced pluripotent stem cell–derived cardiomyocytes in a 3-dimensional collagen matrix, we show that uniaxial mechanical stress conditioning promotes 2-fold increases in cardiomyocyte and matrix fiber alignment and enhances myofibrillogenesis and sarcomeric banding. Furthermore, cyclic stress conditioning markedly increases cardiomyocyte hypertrophy (2.2-fold) and proliferation rates (21%) versus unconditioned constructs. Addition of endothelial cells enhances cardiomyocyte proliferation under all stress conditions (14% to 19%), and addition of stromal supporting cells enhances formation of vessel-like structures by ≈10-fold. Furthermore, these optimized human cardiac tissue constructs generate Starling curves, increasing their active force in response to increased resting length. When transplanted onto hearts of athymic rats, the human myocardium survives and forms grafts closely apposed to host myocardium. The grafts contain human microvessels that are perfused by the host coronary circulation. Conclusions: Our results indicate that both mechanical load and vascular cell coculture control cardiomyocyte proliferation, and that mechanical load further controls the hypertrophy and architecture of engineered human myocardium. Such constructs may be useful for studying human cardiac development as well as for regenerative therapy.
Год издания: 2011
Авторы: Nathaniel L. Tulloch, Veronica Muskheli, Maria V. Razumova, F. Steven Korte, Michael Regnier, Kip D. Hauch, Lil Pabon, Hans Reinecke, Charles E. Murry
Издательство: Lippincott Williams & Wilkins
Источник: Circulation Research
Ключевые слова: Tissue Engineering and Regenerative Medicine, Electrospun Nanofibers in Biomedical Applications, Congenital heart defects research
Другие ссылки: Circulation Research (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)