Construction of a vascularized hydrogel for cardiac tissue formation in a porcine model
| Autor: | Winston Shim, Allen Chen, K P Myu Mai Ja, Chrishan J A Ramachandra, Steve Oh, Kee Pah Lim, Sherwin Ting, Ashish Mehta, Shi Qi Li, Philip Wong, Nicole Tee |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cardiac function curve Pathology medicine.medical_specialty Angiogenesis Swine Human Embryonic Stem Cells Induced Pluripotent Stem Cells Biomedical Engineering Medicine (miscellaneous) 030204 cardiovascular system & hematology Fibrin Cell Line Biomaterials Cell therapy Neovascularization 03 medical and health sciences 0302 clinical medicine Troponin I medicine Animals Humans Myocytes Cardiac Induced pluripotent stem cell biology Chemistry Myocardium Cell Differentiation Hydrogels Embryonic stem cell 030104 developmental biology biology.protein Collagen medicine.symptom |
| Zdroj: | Journal of tissue engineering and regenerative medicine. 12(4) |
| ISSN: | 1932-7005 |
| Popis: | 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 macrosized 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 remodelled collagen matrix. Nevertheless, no significant changes in intraconstruct density of cardiomyocytes were observed in the myocardial-grafted constructs (human embryonic stem cell [hESC]-derived cardiomyocyte [n = 4]: 70.5 ± 22.8 troponin I+ cardiomyocytes/high power field [HPF]) as compared to peripherally implanted constructs (hESC-derived cardiomyocyte [n = 4]: 59.0 ± 19.6 troponin I+ cardiomyocytes/HPF; human induced pluripotent stem cell-derived cardiomyocyte [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 < .05), microvascular maturation (82.8 ± 24.7 mature microvessels/mm2 , p < .05), and tissue-like formation whereas the peripherally implanted constructs of hESC-derived cardiomyocyte (168.3 ± 98.2 microvessels/mm2 tissue and 68.1 ± 33.4 mature microvessels/mm2 ) and human induced pluripotent stem cell-derived cardiomyocyte (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 human fibroblasts (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 centimetre-sized human cardiac construct that may spur novel approaches in cardiac tissue replacement strategy. |
| Databáze: | OpenAIRE |
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