Genetically Modified Human Umbilical Cord Perivascular Cells for Bone Tissue Engineering

INTRODUCTION: Tissue engineering and ex vivo gene therapy can be used synergically as a tool to regenerate bone that overcomes the problems of currently available bone replacements. Recently, in our lab a new source of mesenchymal stem cells (MSCs) has been found in the umbilical cord; Human Umbilical Cord Perivascular cells (HUCPVCs) provide an alternative to bone marrow derived MSCs. Due to their high proportion of colony forming unit-fibroblast, low doubling time (1), no telomerase activity and immunoprivileged phenotype (in vitro) (2), they are an excellent source for cell based tissue engineering strategies. Thus, our goal is to engineer an osteogenic/osteoinductive cell population, by genetically modifying HUCPVCs to express four bone formation related genes: vascular endothelial growth factor A (VEGF-A) acts as a mitogenic and chemoattractant for endothelial cells during angiogenesis and vasculogenesis; bone morphogenetic protein 2 (BMP 2) most widely used growth factor to stimulate osteoblastic differentiation, acts in autocrine and paracrine manner by interacting with cell-surface receptors and triggering an intracellular signaling cascade; runt-related transcription factor 2 (Runx2) essential for osteoblast differentiation and, endochondral and intramembranous bone formation and turnover; and Osterix (OSX/SP7) transcription factor required for osteoblast differentiation and bone formation, commits osteochondroprogenitor cells to the osteoblast lineage.