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Author Notes:

Correspondence should be addressed to Michael E. Davis; michael.davis@bme.emory.edu

The authors would like to acknowledge Dr. Ashley Brown for her silanization protocol.

Competing Interests: Dr. Christman is a cofounder, board member, and holds equity in Ventrix, Inc.

Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

Subjects:

Research Funding:

This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant no. DGE-1148903 (to Kristin M. French) and the NIH (R01HL113468 to Karen L. Christman).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell & Tissue Engineering
  • Cell Biology
  • STEM-CELLS
  • MYOCARDIAL-INFARCTION
  • C-KIT(+) CELLS
  • MOUSE HEART
  • MATRIX
  • CARDIOMYOCYTES
  • PROLIFERATION
  • DIFFERENTIATION
  • CONNEXIN-43
  • EXPRESSION
  • Cardiology

Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro

Tools:

Journal Title:

Stem Cells International

Volume:

Volume 2016

Publisher:

, Pages 8364382-8364382

Type of Work:

Article | Final Publisher PDF

Abstract:

Cardiac progenitor cells (CPCs) have rapidly advanced to clinical trials, yet little is known regarding their interaction with the microenvironment. Signaling cues present in the microenvironment change with development and disease. This work aims to assess the influence of two distinct signaling moieties on CPCs: cyclic biaxial strain and extracellular matrix. We evaluate four endpoints for improving CPC therapy: paracrine signaling, proliferation, connexin43 expression, and alignment. Vascular endothelial growth factor A (about 900 pg/mL) was secreted by CPCs cultured on fibronectin and collagen I. The application of mechanical strain increased vascular endothelial growth factor A secretion 2-4-fold for CPCs cultured on poly-L-lysine, laminin, or a naturally derived cardiac extracellular matrix. CPC proliferation was at least 25% higher on fibronectin than that on other matrices, especially for lower strain magnitudes. At 5% strain, connexin43 expression was highest on fibronectin. With increasing strain magnitude, connexin43 expression decreased by as much as 60% in CPCs cultured on collagen I and a naturally derived cardiac extracellular matrix. Cyclic mechanical strain induced the strongest CPC alignment when cultured on fibronectin or collagen I. This study demonstrates that culturing CPCs on fibronectin with 5% strain magnitude is optimal for their vascular endothelial growth factor A secretion, proliferation, connexin43 expression, and alignment.

Copyright information:

© 2016 Kristin M. French et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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