Porcine Umbilical Cord Perivascular Cells for Preclinical Testing of Tissue-Engineered Heart Valves

Many children born with congenital heart disease need a heart valve repair or replacement. Currently available repair materials and valve replacements are incapable of growth, repair, and adaptation, rendering them inadequate for growing children. Heart valve tissue engineering (HVTE) aims to develop living replacement valves that can meet these needs. Among numerous cell sources for in vitro HVTE, umbilical cord perivascular cells (UCPVCs) are particularly attractive because they are autologous, readily available, and have excellent regenerative capacity. As an essential step toward preclinical testing of heart valves engineered from UCPVCs, the goal of this study was to establish methods to isolate, expand, and promote extracellular matrix (ECM) synthesis by UCPVCs from pigs (porcine umbilical cord perivascular cells [pUCPVCs]), as a relevant preclinical model. We determined that Dulbecco's modified Eagle's medium with 20% fetal bovine serum supported isolation and substantial expansion of pUCPVCs, whereas media designed for human mesenchymal stromal cell (MSC) expansion did not. We further demonstrated the capacity of pUCPVCs to synthesize the main ECM components of heart valves (collagen type I, elastin, and glycosaminoglycans), with maximal collagen and elastin per-cell production occurring in serum-free culture conditions using StemMACS (TM) MSC Expansion Media. Altogether, these results establish protocols that enable the use of pUCPVCs as a viable cell source for preclinical testing of engineered heart valves.

Automated summary

This study aimed to establish methods for isolating, expanding, and promoting ECM synthesis by pUCPVCs as a relevant preclinical model for engineered heart valves. The results demonstrated the potential of pUCPVCs to synthesize key ECM components of heart valves under specific culture conditions, providing protocols for the use of pUCPVCs as a viable cell source for preclinical testing.