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Author Notes:

Michael E. Davis, Ph.D, Assistant Professor of Biomedical Engineering and Medicine, The Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 101 Woodruff Circle, Suite 2001, Atlanta, GA 30322, USA, michael.davis@bme.emory.edu, Telephone: (404) 727-9858, Fax: (404) 727-9873

Dr. Christman has an equity interest in Ventrix, Inc., a company that may potentially benefit from the research results, and also serves on the company’s Scientific Advisory Board.

The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies.

Subjects:

Research Funding:

This work has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN268201000043C to MED, a DuPont Young Faculty Award to HL, NHLBI R21HL104493 to KLC, an American Heart Association predoctoral fellowship 11PRE7840078 to AVB.

This material is also based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1148903 to KMF.

Keywords:

  • Science & Technology
  • Technology
  • Engineering, Biomedical
  • Materials Science, Biomaterials
  • Engineering
  • Materials Science
  • Extracellular matrix
  • Progenitor cell
  • Cell adhesion
  • Cell proliferation
  • Gene expression
  • RANDOMIZED PHASE-1 TRIAL
  • MESENCHYMAL STEM-CELLS
  • MYOCARDIAL-INFARCTION
  • ADULT MYOCARDIUM
  • HEART-FAILURE
  • DIFFERENTIATION
  • CARDIOMYOCYTES
  • REGENERATION
  • TRANSPLANTATION
  • MULTIPOTENT

A Naturally-Derived Cardiac Extracellular Matrix Enhances Cardiac Progenitor Cell Behavior In Vitro

Tools:

Journal Title:

Acta Biomaterialia

Volume:

Volume 8, Number 12

Publisher:

, Pages 4357-4364

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Myocardial infarction (MI) produces a collagen scar, altering the local microenvironment and impeding cardiac function. Cell therapy is a promising therapeutic option to replace the billions of myocytes lost following MI. Despite early successes, chronic function remains impaired and is likely a result of poor cellular retention, proliferation, and differentiation/ maturation. While some efforts to deliver cells with scaffolds have attempted to address these shortcomings, they lack the natural cues required for optimal cell function. The goal of this study was to determine whether a naturally derived cardiac extracellular matrix (cECM) could enhance cardiac progenitor cell (CPC) function in vitro. CPCs were isolated via magnetic sorting of c-kit + cells and were grown on plates coated with either cECM or collagen I (Col). Our results show an increase in early cardiomyocyte markers on cECM compared with Col, as well as corresponding protein expression at a later time. CPCs show stronger serum-induced proliferation on cECM compared with Col, as well as increased resistance to apoptosis following serum starvation. Finally, a microfluidic adhesion assay demonstrated stronger adhesion of CPCs to cECM compared with Col. These data suggest that cECM may be optimal for CPC therapeutic delivery, as well as providing potential mechanisms to overcome the shortcomings of naked cell therapy.

Copyright information:

© 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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