MSC Functional Phenotype: Assay, Age and Source Dependence

Abstract

We recently reported the use of human umbilical cord perivascular cells (HUCPVCs), delivered in a collagen sponge, in the healing of calvarial osteotomies in immune-suppressed rats, following their osteogenic differentiation in vitro. We compared these cells with a human bone marrow (BM) immortalized cell line, and also used conditioned medium from the latter to stimulate the osteogenic differentiation of the HUCPVCs. Our results showed that HUCPVCs provided statistically significant bony repair compared to controls, but failed to show osteogenic differentiation in vitro. On the contrary, BM cells exhibited high levels of alkaline phosphatase expression in vitro, in osteogenic assays, but when loaded onto collagen scaffolds and implanted did not produce a statistically different amount of bone from either sham or collagen-only controls. Our results demonstrated that the in vitro assays employed did not predict in vivo outcomes, and that the BM-MSC cell line employed, or CM from such cells, provided no osteogenic advantage over the use of HUCPVCs alone in vivo. Here, we discuss these findings in light of the contradictory findings of the functional phenotype of MSC within the context of the assay employed, the age of the donor, and the tissue source of the cells. From a therapeutic perspective, it is clear that only in vivo assays should be employed as predictors of clinical performance and that cells sourced from tissue originating from younger donors may be functionally more potent than adult tissue derived MSC sources.