HUMAN iPSC ENGINEERED CARDIAC TISSUE PLATFORM FAITHFULLY MODELS IMPORTANT CARDIAC PHYSIOLOGY,American Journal of Physiology-Heart and Circulatory Physiology

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HUMAN iPSC ENGINEERED CARDIAC TISSUE PLATFORM FAITHFULLY MODELS IMPORTANT CARDIAC PHYSIOLOGY
American Journal of Physiology-Heart and Circulatory Physiology ( IF 4.8 ) Pub Date : 2021-02-19 , DOI: 10.1152/ajpheart.00941.2020
Willem J de Lange ₁ , Emily T Farrell ₁ , Caroline R Kreitzer ₁ , Derek R Jacobs ₁ , Di Lang ₂ , Alexey V Glukhov ₂ , J Carter Ralphe ₁

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Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CM) may provide an important bridge between animal models and intact human myocardium. Fulfilling this potential is hampered by their relative immaturity. hiPSC-CMs grown in monolayer culture lack a t-tubular system, have rudimentary intracellular calcium-handling systems, express predominantly embryonic sarcomeric protein isoforms, and preferentially use glucose as energy substrate. Culturing hiPSC-CM in a 3D environment and the addition of nutritional, pharmacologic and electromechanical stimuli have proven to be beneficial for maturation. We present an assessment of a model in which hiPSC-CMs and hiPSC-derived cardiac fibroblasts are co-cultured in a 3D fibrin matrix to form human engineered cardiac tissue constructs (hECT).The hECT respond to physiological stimuli, including stretch, frequency and β-adrenergic stimulation, develop a t-tubular system, and demonstrate calcium-handling and contractile kinetics that compare favorably with ventricular human myocardium. Transcript levels of genes involved in calcium-handling and contraction are increased. These markers of maturation become more robust over a short period of time in culture (6 weeks vs. 2 weeks in hECT). A comparison of the hECT molecular and performance variables with those of human cardiac tissue and other available engineered tissue platforms is provided to highlight strengths and weaknesses of these preparations. Important and noteworthy aspects of this human cardiac model system are its reliance on 'off-the-shelf' equipment, ability to provide detailed physiological performance data, and the ability to achieve a relatively mature cardiac physiology without additional nutritional, pharmacological and electromechanical stimuli that may elicit unintended effects on function.

更新日期：2021-02-19

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