A naturally derived cardiac extracellular matrix enhances cardiac progenitor cell behavior in vitro

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 attempt 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 to COL, as well as corresponding protein expression later. CPCs show stronger serum-induced proliferation on cECM as compared to 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 provide potential mechanisms for the shortcomings in naked cell therapy.

Polyurethane-based scaffolds for myocardial tissue engineering

“…However, quantitative evaluation of CPC behaviour in contact with scaffolds showed that they did not proliferate after 1-14 days of culture time. In the future, cell behaviour could be further improved by scaffold surface functionalization with bioactive peptides/ proteins of the natural cardiac extracellular matrix (ECM) [12].…”

Tissue-Specific Effects of Esophageal Extracellular Matrix

“…Recent work has described the potential benefits of ECM scaffold materials derived from homologous tissue versus heterologous tissue when used in selected anatomic locations. 2,[4][5][6][7][8][9][10][11] The homologous ECM can preferentially maintain tissuespecific cell phenotypes, [4][5][6][7] promote cell proliferation, 6,8 induce tissue-specific differentiation, 9 and enhance the chemotaxis of stem cells. 2,10,12 However, the preference or necessity for tissue-specific ECM has not been shown for all therapeutic applications.…”

Fate of Distal Lung Epithelium Cultured in a Decellularized Lung Extracellular Matrix

“…Both of these factors have been shown to promote the tissue-specific cell phenotype and function. [24][25][26][27][28] Clearly, in the experiments presented here, the ECM is not sufficient under the culture conditions used (DMEM + 10% FBS, perfusion, no ventilation) to maintain neonatal, rat lung epithelial phenotypes. Instead, these cells appear to undergo an EMT.…”