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Gelatin Based Polymer Cell Coating Improves Bone Marrow-Derived Cell Retention in the Heart after Myocardial Infarction

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Abstract

Background

Acute myocardial infarction (AMI) and the ensuing ischemic heart disease are approaching an epidemic state. Limited stem cell retention following intracoronary administration has reduced the clinical efficacy of this novel therapy. Polymer based cell coating is biocompatible and has been shown to be safe. Here, we assessed the therapeutic utility of gelatin-based biodegradable cell coatings on bone marrow derived cell retention in ischemic heart.

Methods

Gelatin based cell coatings were formed from the surface-mediated photopolymerization of 3% gelatin methacrylamide and 1% PEG diacrylate. Cell coating was confirmed using a multimodality approach including flow cytometry, imaging flow cytometry (ImageStream System) and immunohistochemistry. Biocompatibility of cell coating, metabolic activity of coated cells, and the effect of cell coating on the susceptibility of cells for engulfment were assessed using in vitro models. Following myocardial infarction and GFP+ BM-derived mesenchymal stem cell transplantation, flow cytometric and immunohistochemical assessment of retained cells was performed.

Results

Coated cells are viable and metabolically active with coating degrading within 72 h in vitro. Importantly, cell coating does not predispose bone marrow cells to aggregation or increase their susceptibility to phagocytosis. In vitro and in vivo studies demonstrated no evidence of heightened immune response or increased phagocytosis of coated cells. Cell transplantation studies following myocardial infarction proved the improved retention of coated bone marrow cells compared to uncoated cells.

Conclusion

Gelation based polymer cell coating is biologically safe and biodegradable. Therapies employing these strategies may represent an attractive target for improving outcomes of cardiac regenerative therapies in human studies.

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Acknowledgements

Dr. Abdel-Latif is supported by the University of Kentucky COBRE Early Career Program (P20 GM103527) and the NIH Grant R01 HL124266. This work was partially supported by R01 HL127682 and the National Science Foundation under Award CBET-1351531.

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  1. Anuhya Gottipati and Lakshman Chelvarajan contributed equally to this work.

Authors and Affiliations

  1. Department of Chemical and Materials Engineering, University of Kentucky, Lexington, KY, USA

    Anuhya Gottipati, Calvin F. Cahall, Cong Li & Brad J. Berron

  2. Gill Heart and Vascular Institute and Division of Cardiovascular Medicine, University of Kentucky and the Lexington VA Medical Center, Lexington, KY, USA

    Lakshman Chelvarajan, Hsuan Peng, Himi Tripathi, Ahmed Al-Darraji, Shaojing Ye, Eman Elsawalhy & Ahmed Abdel-Latif

  3. MilliporeSigma, Seattle, WA, 98119, USA

    Raymond Kong

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  1. Anuhya Gottipati
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Gottipati, A., Chelvarajan, L., Peng, H. et al. Gelatin Based Polymer Cell Coating Improves Bone Marrow-Derived Cell Retention in the Heart after Myocardial Infarction. Stem Cell Rev and Rep 15, 404–414 (2019). https://doi.org/10.1007/s12015-018-9870-5

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