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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Wiley
2016-01-01
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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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id | doaj-art-6de0e541fe5a45b19336e150975bb8d6 |
institution | Kabale University |
issn | 1687-966X 1687-9678 |
language | English |
publishDate | 2016-01-01 |
publisher | Wiley |
record_format | Article |
series | Stem Cells International |
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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