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 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.
Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA 30322, USA; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Kristin M
0000-0002-1055-5689
KM
French
Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Joshua T
0000-0001-7389-5245
JT
Maxwell
Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA 30322, USA; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Srishti
0000-0001-6315-2990
S
Bhutani
Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA 30322, USA.
Shohini
S
Ghosh-Choudhary
Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA 30322, USA.
Marcos J
MJ
Fierro
Department of Bioengineering, Sanford Consortium for Regenerative Medicine, University of California, La Jolla, San Diego, CA 92037, USA.
Todd D
0000-0002-8090-0134
TD
Johnson
Department of Bioengineering, Sanford Consortium for Regenerative Medicine, University of California, La Jolla, San Diego, CA 92037, USA.
Karen L
KL
Christman
Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA 30322, USA; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
W Robert
WR
Taylor
Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA 30322, USA; Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA; Children's Heart Research and Outcomes Center, Emory University and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
Michael E
0000-0002-9239-2886
ME
Davis