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Hybrid Gel Composed of Native Heart Matrix and Collagen Induces Cardiac Differentiation of Human Embryonic Stem Cells without Supplemental Growth Factors

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Abstract

Our goal was to assess the ability of native heart extracellular matrix (ECM) to direct cardiac differentiation of human embryonic stem cells (hESCs) in vitro. In order to probe the effects of cardiac matrix on hESC differentiation, a series of hydrogels was prepared from decellularized ECM from porcine hearts by mixing ECM and collagen type I at varying ratios. Maturation of cardiac function in embryoid bodies formed from hESCs was documented in terms of spontaneous contractile behavior and the mRNA and protein expression of cardiac markers. Hydrogel with high ECM content (75% ECM, 25% collagen, no supplemental soluble factors) increased the fraction of cells expressing cardiac marker troponin T, when compared with either hydrogel with low ECM content (25% ECM, 75% collagen, no supplemental soluble factors) or collagen hydrogel (100% collagen, with supplemental soluble factors). Furthermore, cardiac maturation was promoted in high-ECM content hydrogels, as evidenced by the striation patterns of cardiac troponin I and by upregulation of Cx43 gene. Consistently, high-ECM content hydrogels improved the contractile function of cardiac cells, as evidenced by increased numbers of contracting cells and increased contraction amplitudes. The ability of native ECM hydrogel to induce cardiac differentiation of hESCs without the addition of soluble factors makes it an attractive biomaterial system for basic studies of cardiac development and potentially for the delivery of therapeutic cells into the heart.

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Acknowledgment

The authors gratefully acknowledge the funding support of this work by the NIH (grants HL076485 and EB002520 to GVN), NYSTEM (grant C026721 to DOF), Columbia University and Helmsley Foundation (grant CU11-0138 to GVN).

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  1. Department of Biomedical Engineering, Columbia University, 622 west 168th Street, VC12-234, New York, NY, 10032, USA

    Yi Duan, Zen Liu, John O’Neill, Leo Q. Wan, Donald O. Freytes & Gordana Vunjak-Novakovic

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  1. Yi Duan
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  2. Zen Liu
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  3. John O’Neill
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  4. Leo Q. Wan
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  6. Gordana Vunjak-Novakovic
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Correspondence to Gordana Vunjak-Novakovic.

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Duan, Y., Liu, Z., O’Neill, J. et al. Hybrid Gel Composed of Native Heart Matrix and Collagen Induces Cardiac Differentiation of Human Embryonic Stem Cells without Supplemental Growth Factors. J. of Cardiovasc. Trans. Res. 4, 605–615 (2011). https://doi.org/10.1007/s12265-011-9304-0

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