title: The effect of donor variation and senescence on endothelial differentiation of human mesenchymal stromal cells.
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.
authors.affiliation: 1 Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede, The Netherlands .
authors.forename: Karolina Janeczek
authors.initials: KJ
authors.lastname: Portalska
authors.forename: Nathalie
authors.initials: N
authors.lastname: Groen
authors.forename: Guido
authors.initials: G
authors.lastname: Krenning
authors.forename: Nicole
authors.initials: N
authors.lastname: Georgi
authors.forename: Anouk
authors.initials: A
authors.lastname: Mentink
authors.forename: Martin C
authors.initials: MC
authors.lastname: Harmsen
authors.forename: Clemens
authors.initials: C
authors.lastname: van Blitterswijk
authors.forename: Jan
authors.initials: J
authors.lastname: de Boer
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D016133:Polymerase Chain Reaction