Transdifferentiation potentiality of human Wharton's jelly stem cells towards vascular endothelial cells

Abstract

Human Wharton's jelly stem cells (HWJSC) emerged as a potential source of viable cells for use in tissue engineering. In this work, we have analyzed the transdifferentiation capabilities of HWJSC towards transdifferentiated endothelial-like cells (Tr-ELC) in order to establish the potential usefulness of these cells in vascular tissue engineering. Our results show that Tr-ELC became more polygonal and less proliferative than HWJSC, resembling the structure and proliferation rate of the endothelial cells. In addition, the markers of mesenchymal undifferentiation CD9, E-cad, PODXL, and SSEA-4 are downregulated in Tr-ELC, suggesting that these cells can be in the process of adult differentiation. Besides, RT-PCR and microarray analyses revealed that some genes with a role in defining the endothelial phenotype and structure are upregulated (VEGF-R1, EDF1, AAMP, CD31, CD34, CDH5, and ICAM2) or downregulated (VEGF) in Tr-ELC, although a number of genes related to relevant endothelial cell functions (CD36, ECE2, VWF, THBD, PGI2, ECE1, and ACE) did not change or were only partially induced. All this implies that HWJSC are able to efficiently transdifferentiate towards Tr-ELC at the phenotypical level following a hierarchical pattern of gene activation, with an earlier induction of morphological and phenotypical genes.