Construction of a Vascularized Hydrogel for Cardiac Tissue Formation in a Porcine Model

Myu Mai Ja, K.P. and Lim, Kee Pah and Chen, Allen and Ting, Sherwin and Li, Shi Qi and Tee, Nicole and Ramachandra, Chrishan and Mehta, Ashish and Wong, Philip and Oh, Steve and Shim, Winston (2018) Construction of a Vascularized Hydrogel for Cardiac Tissue Formation in a Porcine Model. Journal of Tissue Engineering and Regenerative Medicine, 2018. pp.1-10. ISSN 19326254 (Not OA)

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Link to published document: http://doi.org/10.1002/term.2634

Abstract

Replacing cardiac tissues lost to myocardial infarction remains a therapeutic goal for regenerative therapy in recovering cardiac function. We assessed the feasibility of constructing a macro-sized human cardiac tissue construct using pluripotent stem cell-derived cardiomyocytes or control fibroblasts infused fibrin/collagen hydrogel and performed ectopic implantation in peripheral vascular system of a porcine model for 3 weeks. Finally, an optimized vascularized cardiac construct was explanted and grafted onto porcine myocardium for 2 weeks. Myocardial grafted human cardiac constructs showed a nascent tissue-like organization with aligned cardiomyocytes within the remodeled collagen matrix. Nevertheless, no significant changes in intra-construct density of cardiomyocytes were observed in the myocardial grafted constructs (hESC-CM (n=4): 70.5 ± 22.8 troponin I+ cardiomyocytes/HPF) as compared to peripherally implanted constructs (hESC-CM (n=4): 59.0 ± 19.6 troponin I+ cardiomyocytes/HPF; hiPSC-CM (n=3): 50.9 ± 8.5 troponin I+ cardiomyocytes/HPF, p=ns). However, the myocardial grafted constructs showed an increased in neovascularization (194.4 ± 24.7 microvessels/mm2 tissue, p<0.05), microvascular maturation (82.8 ± 24.7 mature microvessels/mm2 , p<0.05) and tissue-like formation whereas the peripherally implanted constructs of hESC-CM (168.3 ± 98.2 microvessels/mm2 tissue and 68.1 ± 33.4 mature microvessels/mm2 ) and hiPSC-CM (86.8 ± 57.4 microvessels/mm2 tissue and 22.0 ± 32.7 mature microvessels/mm2 ) were not significantly different in vascularized response when compared to the control hFB (n=3) constructs (65.6 ± 34.1 microvessels/mm2 tissue and 30.7 ± 20.7 mature microvessels/mm2 ). We presented results on technical feasibility and challenges of grafting vascularized centimeter-sized human cardiac construct that may spur novel approaches in cardiac tissue replacement strategy.

Item Type: Article
Keywords: Innovation Centre
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 01 Jan 2018 22:22
Last Modified: 30 Jan 2018 01:04
URI: https://eprints.victorchang.edu.au/id/eprint/678

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