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

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 mo...

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Main Authors: Kristin M. French, Joshua T. Maxwell, Srishti Bhutani, Shohini Ghosh-Choudhary, Marcos J. Fierro, Todd D. Johnson, Karen L. Christman, W. Robert Taylor, Michael E. Davis
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/8364382
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author Kristin M. French
Joshua T. Maxwell
Srishti Bhutani
Shohini Ghosh-Choudhary
Marcos J. Fierro
Todd D. Johnson
Karen L. Christman
W. Robert Taylor
Michael E. Davis
author_facet Kristin M. French
Joshua T. Maxwell
Srishti Bhutani
Shohini Ghosh-Choudhary
Marcos J. Fierro
Todd D. Johnson
Karen L. Christman
W. Robert Taylor
Michael E. Davis
author_sort Kristin M. French
collection DOAJ
description 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.
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spelling doaj-art-6de0e541fe5a45b19336e150975bb8d62025-02-03T05:52:53ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/83643828364382Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In VitroKristin M. French0Joshua T. Maxwell1Srishti Bhutani2Shohini Ghosh-Choudhary3Marcos J. Fierro4Todd D. Johnson5Karen L. Christman6W. Robert Taylor7Michael E. Davis8Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA 30322, USADivision of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USAWallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA 30322, USAWallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA 30322, USAWallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Bioengineering, Sanford Consortium for Regenerative Medicine, University of California, La Jolla, San Diego, CA 92037, USADepartment of Bioengineering, Sanford Consortium for Regenerative Medicine, University of California, La Jolla, San Diego, CA 92037, USAWallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA 30322, USAWallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA 30322, USACardiac 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.http://dx.doi.org/10.1155/2016/8364382
spellingShingle Kristin M. French
Joshua T. Maxwell
Srishti Bhutani
Shohini Ghosh-Choudhary
Marcos J. Fierro
Todd D. Johnson
Karen L. Christman
W. Robert Taylor
Michael E. Davis
Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro
Stem Cells International
title Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro
title_full Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro
title_fullStr Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro
title_full_unstemmed Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro
title_short Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro
title_sort fibronectin and cyclic strain improve cardiac progenitor cell regenerative potential in vitro
url http://dx.doi.org/10.1155/2016/8364382
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