Evaluation of Placental Mesenchymal Stem Cell Sheets for Myocardial Repair and Regeneration

Abstract

Surgical solutions for congenital heart defects include implantation of synthetic materials that do not grow with the child. Reoperation associated with use of such materials would be greatly reduced through the use of live scaffold-less autologous tissue patches constructed from stacked cell sheets that have growth potential. We assessed placental mesenchymal stem cells (pMSCs) as a potential cell source for cardiac repair and regeneration. We evaluated pMSCs for their differentiation capacity into cardiomyocytes by comparing protein expression of cardiac troponin I, sarcomeric α-actinin, connexin 43, and Nkx2.5 before and after pMSCs were treated with cardiomyocyte differentiation medium. We used a migration assay to monitor undifferentiated pMSC effects on cardiac cell movement and proliferation as measured by ki67 staining. Undifferentiated pMSCs were grown into cell sheets that could be stretched with a uniaxial tensile tester to quantify single layer cell sheet modulus and ultimate tensile strength. We found that pMSC cardiac protein content was enhanced by differentiation medium treatment, but no beating cells were produced. However, undifferentiated pMSCs improved migration and proliferation of a cardiac cell population. Undifferentiated pMSCs formed intact aligned cell sheets. Experimental results presented provide sufficient evidence to warrant further pursuit of undifferentiated pMSC cellular sheets as surgical implants for pediatric cardiac regeneration and repair solutions. This work explores placental tissue as a cell source for fabrication of tissue-engineered surgical patches for myocardial repair of congenital heart defects. This study demonstrates promising findings for the clinically driven evaluation of the cell source as defined by potential cardiac benefit, compatibility, cell source availability, and implant deliverability. It documents methods for the isolation of mesenchymal stem cells from human placental amnion and chorion tissues, characterization of these cells, and eventual cell sheet growth that can be leveraged going forward for patch fabrication. It establishes support to continue pursuing the placenta as a valuable cell source for myocardial repair.