Pre-Conditioning Stem Cells in a Biomimetic Environment for Enhanced Cardiac Tissue Repair: In Vitro and In Vivo Analysis
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Issue Date
2018-10-01Author
Chakravarti, Aparna R.
Pacelli, Settimio
Alam, Perwez
Bagchi, Samik
Modaresi, Saman
Czirok, Andras
Ahmed, Rafeeq P. H.
Paul, Arghya
Publisher
Springer
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Rights
© Biomedical Engineering Society 2018
Metadata
Show full item recordAbstract
Introduction
Stem cell-based therapies represent a valid approach to restore cardiac function due to their beneficial effect in reducing scar area formation and promoting angiogenesis. However, their translation into the clinic is limited by the poor differentiation and inability to secrete sufficient therapeutic factors. To address this issue, several strategies such as genetic modification and biophysical pre-conditioning have been used to enhance the efficacy of stem cells for cardiac tissue repair.Methods
In this study, a biomimetic approach was used to mimic the natural mechanical stimulation of the myocardium tissue. Specifically, human adipose-derived stem cells (hASCs) were cultured on a thin gelatin methacrylamide (GelMA) hydrogel disc and placed on top of a beating cardiomyocyte layer. qPCR studies and metatranscriptomic analysis of hASCs gene expression were investigated to confirm the correlation between mechanical stimuli and cardiomyogenic differentiation. In vivo intramyocardial delivery of pre-conditioned hASCs was carried out to evaluate their efficacy to restore cardiac function in mice hearts post-myocardial infarction.Results
The cyclic strain generated by cardiomyocytes significantly upregulated the expression of both mechanotransduction and cardiomyogenic genes in hASCs as compared to the static control group. The inherent angiogenic secretion profile of hASCs was not hindered by the mechanical stimulation provided by the designed biomimetic system. Finally, in vivo analysis confirmed the regenerative potential of the pre-conditioned hASCs by displaying a significant improvement in cardiac function and enhanced angiogenesis in the peri-infarct region.Conclusion
Overall, these findings indicate that cyclic strain provided by the designed biomimetic system is an essential stimulant for hASCs cardiomyogenic differentiation, and therefore can be a potential solution to improve stem-cell based efficacy for cardiovascular repair.
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Citation
Chakravarti, A. R., Pacelli, S., Alam, P., Bagchi, S., Modaresi, S., Czirok, A., … Paul, A. (2018). Pre-Conditioning Stem Cells in a Biomimetic Environment for Enhanced Cardiac Tissue Repair: In Vitro and In Vivo Analysis. Cellular and molecular bioengineering, 11(5), 321–336. doi:10.1007/s12195-018-0543-x
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