Portalska - The Effect of Donor Variation and Senescence on Endothelial Differentiation of Human Mesenchymal Stromal Cells

Karolina Janeczek Portalska, Nathalie Groen, Guido Krenning, Nicole Georgi, Anouk Mentink, Martin C. Harmsen, Clemens van Blitterswijk, and Jan de Boer

Tissue Engineering Part A - 2013

Abstract

Application of autologous cells is considered for a broad range of regenerative therapies because it is not
surrounded by the immunological and ethical issues of allo- or xenogenic cells. However, isolation, expansion,
and application of autologous cells do suffer from variability in therapeutic efficacy due to donor to donor
differences and due to prolonged culture. One important source of autologous cells is mesenchymal stromal cells
(MSCs), which can differentiate toward endothelial-like cells, thus making them an ideal candidate as cell source
for tissue vascularization. Here we screened MSCs from 20 donors for their endothelial differentiation capacity
and correlated it with the gene expression profile of the whole genome in the undifferentiated state. Cells of all
donors were able to form tubes on Matrigel and induced the expression of endothelial genes, although with
quantitative differences. In addition, we analyzed the effect of prolonged in vitro expansion on the multipotency
of human MSCs and found that endothelial differentiation is only mildly sensitive to expansion-induced loss of
differentiation as compared to osteogenic and adipogenic differentiation. Our results show the robustness of the
endothelial differentiation protocol and the gene expression data give insight in the differences in endothelial
differentiation between donors.