Engineering Mature, Contractile Cardiac Tissue
Using human induced pluripotent stem cells (hiPSCs) to derive cardiomyocytes, we form engineered cardiac tissue (ECT) and stimulate them mechanically, electrically, and biochemically to promote cardiomyocyte maturation in vitro. A combination of approaches enables targeting unique cellular processes to induce maturation. Biochemical stimulation with insulin-like growth factor-1 (IGF1) and neuregulin-1 (NRG1) induces cardiomyocyte proliferation and promotes maturation of metabolic pathways and contractility to enable a positive force-frequency response (Rupert et al 2017 Stem Cells Int.). Purification of cardiomyocytes, co-culture of cardiomyocytes with other cardiac cell types, and understanding the non-myocyte hiPSC-derived population alters excitation-contraction coupling and the biophysics of contraction (Rupert et al 2020 Plos One, Rupert et al 2020 Stem Cells Int). Embedding of wet-spun collagen microfibers in a defined, anisotropic architecture aligns myofilaments and sarcomeres in ECTs (Kaiser et al 2019 ACS Biomater Sci Eng). With collaborators in the Srivastava lab at Brown, we developed a three-dimensional strain continuum predictive model to allow for micro-structural design optimization and analysis of effectiveness of the implanted patches (Bai et al 2021), and with collaborators in the Callanan lab at the University of Edinburgh, we are utilizing biomaterials beyond collagen in anisotropic scaffolds for applications in the heart and beyond (Reid et al 2021).
Publications:
Reid, J.A., Dwyer, K.D., Schmitt, P.R., Soepriatna, A.H., Coulombe, K., Callanan, A., 2021. Architected fibrous scaffolds for engineering anisotropic tissues. Biofabrication. https://doi.org/10.1088/1758-5090/ac0fc9
Bai, Y., Kaiser, N.J., Coulombe, K.L.K., Srivastava, V., 2021. A continuum model and simulations for large deformation of anisotropic fiber-matrix composites for cardiac tissue engineering. J Mech Behav Biomed Mater 121, 104627. https://doi.org/10.1016/j.jmbbm.2021.104627
Dwyer, K.D., Coulombe, K.L.K., 2021. Cardiac mechanostructure: Using mechanics and anisotropy as inspiration for developing epicardial therapies in treating myocardial infarction. Bioact Mater 6, 2198–2220. https://doi.org/10.1016/j.bioactmat.2020.12.015
Rupert, C.E., Irofuala, C., Coulombe, K.L.K., 2020. Practical adoption of state-of-the-art hiPSC cardiomyocyte differentiation techniques. PLoS One 15, e0230001. https://doi.org/10.1371/journal.pone.0230001
Rupert, C.E., Kim, T.Y., Choi, B.-R., Coulombe, K.L.K., 2020. Human Cardiac Fibroblast Number and Activation State Modulate Electromechanical Function of hiPSC-Cardiomyocytes in Engineered Myocardium. Stem Cells Int 2020, 9363809. https://doi.org/10.1155/2020/9363809
Kaiser, N.J., Bellows, J.A., Kant, R.J., Coulombe, K.L.K., 2019. Digital Design and Automated Fabrication of Bespoke Collagen Microfiber Scaffolds. Tissue Eng Part C Methods 25, 687–700. https://doi.org/10.1089/ten.TEC.2018.0379
Kaiser, N.J., Kant, R.J., Minor, A.J., Coulombe, K.L.K., 2019. Optimizing Blended Collagen-Fibrin Hydrogels for Cardiac Tissue Engineering with Human iPSC-derived Cardiomyocytes. ACS Biomater Sci Eng 5, 887–899. https://doi.org/10.1021/acsbiomaterials.8b01112
Kaiser, N.J., Munarin, F., Coulombe, K.L.K., 2018. Custom Engineered Tissue Culture Molds from Laser etched Masters. J Vis Exp. https://doi.org/10.3791/57239
Liu, M., Shi, G., Zhou, A., Rupert, C.E., Coulombe, K.L.K., Dudley, S.C., 2018. Activation of the unfolded protein response downregulates cardiac ion channels in human induced pluripotent stem cell-derived cardiomyocytes. J Mol Cell Cardiol 117, 62–71. https://doi.org/10.1016/j.yjmcc.2018.02.011
Munarin, F., Kaiser, N.J., Kim, T.Y., Choi, B.-R., Coulombe, K.L.K., 2017. Laser-Etched Designs for Molding Hydrogel-Based Engineered Tissues. Tissue Eng Part C Methods 23, 311–321. https://doi.org/10.1089/ten.TEC.2017.0068
Rupert, C.E., Coulombe, K.L.K., 2017. IGF1 and NRG1 Enhance Proliferation, Metabolic Maturity, and the Force-Frequency Response in hESC-Derived Engineered Cardiac Tissues. Stem Cells Int 2017, 7648409. https://doi.org/10.1155/2017/7648409
Rupert, C.E., Chang, H.H., Coulombe, K.L.K., 2017. Hypertrophy changes 3D shape of hiPSC cardiomyocytes: Implications for cellular maturation in regenerative medicine. Cell Mol Bioeng 10, 54–62. https://doi.org/10.1007/s12195-016-0462-7
Roberts, M.A., Tran, D., Coulombe, K.L.K., Razumova, M., Regnier, M., Murry, C.E., Zheng, Y., 2016. Stromal Cells in Dense Collagen Promote Cardiomyocyte and Microvascular Patterning in Engineered Human Heart Tissue. Tissue Eng Part A 22, 633–644. https://doi.org/10.1089/ten.TEA.2015.0482
Rupert, C.E., Coulombe, K.L., 2015. The roles of neuregulin-1 in cardiac development, homeostasis, and disease. Biomark Insights 10, 1–9. https://doi.org/10.4137/BMI.S20061
Kaiser, N.J., Coulombe, K.L.K., 2015. Physiologically inspired cardiac scaffolds for tailored in vivo function and heart regeneration. Biomed Mater 10, 034003. https://doi.org/10.1088/1748-6041/10/3/034003
Gerbin, K.A., Yang, X., Murry, C.E., Coulombe, K.L.K., 2015. Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts. PLoS One 10, e0131446. https://doi.org/10.1371/journal.pone.0131446
Coulombe, K.L.K., Bajpai, V.K., Andreadis, S.T., Murry, C.E., 2014. Heart regeneration with engineered myocardial tissue. Annu Rev Biomed Eng 16, 1–28. https://doi.org/10.1146/annurev-bioeng-071812-152344
