Pre-Conditioning Stem Cells in a Biomimetic Environment for Enhanced Cardiac Tissue Repair: In Vitro and In Vivo Analysis

Aparna R. Chakravarti, Settimio Pacelli, Perwez Alam, Samik Bagchi, Saman Modaresi, A. Czirók, Rafeeq P.H. Ahmed, Arghya Paul

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalCellular and Molecular Bioengineering
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Biomimetics
Stem Cells
Preconditioning
Stem cells
Cardiac
Repair
Tissue
Efficacy
Angiogenesis
Cardiac Myocytes
Mechanotransduction
In Vitro Techniques
Hydrogel
Cell Differentiation
Myocardial Infarction
Myocardium
Secretion
Gelatin
Cell- and Tissue-Based Therapy
Human

Keywords

  • Angiogenesis
  • Cardiac repair
  • Mechanical stimulation
  • Myogenic differentiation

ASJC Scopus subject areas

  • Modelling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Pre-Conditioning Stem Cells in a Biomimetic Environment for Enhanced Cardiac Tissue Repair : In Vitro and In Vivo Analysis. / Chakravarti, Aparna R.; Pacelli, Settimio; Alam, Perwez; Bagchi, Samik; Modaresi, Saman; Czirók, A.; Ahmed, Rafeeq P.H.; Paul, Arghya.

In: Cellular and Molecular Bioengineering, 01.01.2018.

Research output: Contribution to journalArticle

Chakravarti, Aparna R. ; Pacelli, Settimio ; Alam, Perwez ; Bagchi, Samik ; Modaresi, Saman ; Czirók, A. ; Ahmed, Rafeeq P.H. ; Paul, Arghya. / Pre-Conditioning Stem Cells in a Biomimetic Environment for Enhanced Cardiac Tissue Repair : In Vitro and In Vivo Analysis. In: Cellular and Molecular Bioengineering. 2018.
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AU - Alam, Perwez

AU - Bagchi, Samik

AU - Modaresi, Saman

AU - Czirók, A.

AU - Ahmed, Rafeeq P.H.

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AB - 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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