Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction

Biomaterials. 2015 Aug:61:339-48. doi: 10.1016/j.biomaterials.2015.05.005. Epub 2015 May 28.

Abstract

Cardiac cell therapy suffers from limitations related to poor engraftment and significant cell death after transplantation. In this regard, ex vivo tissue engineering is a tool that has been demonstrated to increase cell retention and survival. The aim of our study was to evaluate the therapeutic potential of a 3D-printed patch composed of human cardiac-derived progenitor cells (hCMPCs) in a hyaluronic acid/gelatin (HA/gel) based matrix. hCMPCs were printed in the HA/gel matrix (30 × 10(6) cells/ml) to form a biocomplex made of six perpendicularly printed layers with a surface of 2 × 2 cm and thickness of 400 μm, in which they retained their viability, proliferation and differentiation capability. The printed biocomplex was transplanted in a mouse model of myocardial infarction (MI). The application of the patch led to a significant reduction in adverse remodeling and preservation of cardiac performance as was shown by both MRI and histology. Furthermore, the matrix supported the long-term in vivo survival and engraftment of hCMPCs, which exhibited a temporal increase in cardiac and vascular differentiation markers over the course of the 4 week follow-up period. Overall, we developed an effective and translational approach to enhance hCMPC delivery and action in the heart.

Keywords: Cardiac progenitor cells; Cardiac regeneration; Cardiac tissue engineering; Heart failure; Tissue printing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Female
  • Gelatin / chemistry*
  • Humans
  • Hyaluronic Acid / chemistry*
  • Mice
  • Mice, SCID
  • Myocardial Infarction / physiopathology*
  • Myocardial Infarction / therapy*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / transplantation*
  • Pericardium / pathology
  • Pericardium / physiopathology
  • Printing, Three-Dimensional
  • Stem Cell Transplantation / methods*
  • Tissue Scaffolds
  • Treatment Outcome

Substances

  • Gelatin
  • Hyaluronic Acid