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Construction of a vascularized hydrogel for cardiac tissue formation in a porcine model.
- Source :
-
Journal of tissue engineering and regenerative medicine [J Tissue Eng Regen Med] 2018 Apr; Vol. 12 (4), pp. e2029-e2038. Date of Electronic Publication: 2018 Jan 10. - Publication Year :
- 2018
-
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 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 <superscript>+</superscript> cardiomyocytes/high power field [HPF]) as compared to peripherally implanted constructs (hESC-derived cardiomyocyte [n = 4]: 59.0 ± 19.6 troponin I <superscript>+</superscript> cardiomyocytes/HPF; human induced pluripotent stem cell-derived cardiomyocyte [n = 3]: 50.9 ± 8.5 troponin I <superscript>+</superscript> cardiomyocytes/HPF, p = ns). However, the myocardial-grafted constructs showed an increased in neovascularization (194.4 ± 24.7 microvessels/mm <superscript>2</superscript> tissue, p < .05), microvascular maturation (82.8 ± 24.7 mature microvessels/mm <superscript>2</superscript> , p < .05), and tissue-like formation whereas the peripherally implanted constructs of hESC-derived cardiomyocyte (168.3 ± 98.2 microvessels/mm <superscript>2</superscript> tissue and 68.1 ± 33.4 mature microvessels/mm <superscript>2</superscript> ) and human induced pluripotent stem cell-derived cardiomyocyte (86.8 ± 57.4 microvessels/mm <superscript>2</superscript> tissue and 22.0 ± 32.7 mature microvessels/mm <superscript>2</superscript> ) were not significantly different in vascularized response when compared to the control human fibroblasts (n = 3) constructs (65.6 ± 34.1 microvessels/mm <superscript>2</superscript> tissue and 30.7 ± 20.7 mature microvessels/mm <superscript>2</superscript> ). 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.<br /> (Copyright © 2017 John Wiley & Sons, Ltd.)
- Subjects :
- Animals
Cell Line
Collagen chemistry
Fibrin chemistry
Human Embryonic Stem Cells cytology
Humans
Induced Pluripotent Stem Cells cytology
Myocardium cytology
Myocytes, Cardiac cytology
Swine
Cell Differentiation
Human Embryonic Stem Cells metabolism
Hydrogels chemistry
Induced Pluripotent Stem Cells metabolism
Myocardium metabolism
Myocytes, Cardiac metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-7005
- Volume :
- 12
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of tissue engineering and regenerative medicine
- Publication Type :
- Academic Journal
- Accession number :
- 29266858
- Full Text :
- https://doi.org/10.1002/term.2634