Deterministic Encapsulation of Human Cardiac Stem Cells in Variable Composition Nanoporous Gel Cocoons To Enhance Therapeutic Repair of Injured Myocardium

ACS Nano. 2018 May 22;12(5):4338-4350. doi: 10.1021/acsnano.7b08881. Epub 2018 Apr 20.

Abstract

Although cocooning explant-derived cardiac stem cells (EDCs) in protective nanoporous gels (NPGs) prior to intramyocardial injection boosts long-term cell retention, the number of EDCs that finally engraft is trivial and unlikely to account for salutary effects on myocardial function and scar size. As such, we investigated the effect of varying the NPG content within capsules to alter the physical properties of cocoons without influencing cocoon dimensions. Increasing NPG concentration enhanced cell migration and viability while improving cell-mediated repair of injured myocardium. Given that the latter occurred with NPG content having no detectable effect on the long-term engraftment of transplanted cells, we found that changing the physical properties of cocoons prompted explant-derived cardiac stem cells to produce greater amounts of cytokines, nanovesicles, and microRNAs that boosted the generation of new blood vessels and new cardiomyocytes. Thus, by altering the physical properties of cocoons by varying NPG content, the paracrine signature of encapsulated cells can be enhanced to promote greater endogenous repair of injured myocardium.

Keywords: biomaterial; cardiac stem cells; exosomes; heart failure; myocardial infarct; nanoporous gel; nanovesicles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Gels / chemistry
  • Gels / pharmacology
  • Humans
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology
  • Myocytes, Cardiac / drug effects*
  • Nanoparticles / chemistry*
  • Particle Size
  • Porosity
  • Surface Properties

Substances

  • Gels