First Trimester Human Umbilical Cord Perivascular Cells Differentiated into Immunoprivileged, Contracting Cardiomyocyte-like Cells in Vitro

Myocardial infarction (MI) is the leading cause of mortality and morbidity worldwide. The extensive loss of cardiomyocutes without replacing them with healthy cells leads to congestive heart disease (CAD). Mesenchymal stromal cells are extensively studied for both allogeneic and autologous tissue regeneration applications due to their availability and beneficial immunomodulatory profile. While MSC based cell therapy is a widely investigated treatment option to substitute highly invasive surgical interventions, their limited differentiation potential restricts applications aiming to replace host cardiomyocytes. The ideal MSC type should have the ability to provide micro- or macro-tissue significant to achieve cardiac regeneration after MI.

We aimed to investigate the cardiomyogenic differentiation potential of first trimester human umbilical cord perivascular cells (FTM HUCPVCs), a novel, young source of immunoprivileged mesenchymal stromal cells. Our aggregation-based differentiation method achieved significantly increased expression of cardiomyocyte markers (cTnT, MYH6, SIRPA, and CX43) in both FTM and term HUCPVCs compared to bone marrow MSCs, while HUCPVCs immunogenicity remained significantly lower as indicated by HLA-A and HLA-G expression levels and significantly lower susceptibility towards T cell mediated cytotoxicity.

FTM HUCPVCs showed increased aggregate formation potential and generated spontaneously contracting cells within 1 week of co-culture with rat cardiac feeder layer. This makes them the first MSC type that displays such ability. Our results indicate that young FTM HUCPVCs have superior cardiomyogenic potential combined with immunopriviledged properties when compared to MSCs of older tissue sources. We postulate that in vitro pre-differentiation of MSCs from young sources – such as FTM HUCPVCs - could be a potential strategy to increase their efficiency in vivo and provide with better treatment strategies for MI.