Mechanical Cyclic Stretch Regulate Angiogenic Abilities of Endothelial Progenitor cells

Abstract

Background & Aim Human endothelial progenitor cells (EPCs) are adult stem cells, located in the bone marrow (BM), peripheral blood, placenta and others. EPCs have important role in tissue regeneration via angiogenesis and vasculogenesis. In response to tissue injury, BM-EPCs mobilize to injury site where various growth factors such as vascular endothelial growth factors (VEGF), stromal derived factor 1 alpha (SDF-1a) are released. At the injured site, EPCs can differentiate into mature endothelial cells (ECs) and then directly incorporate into the blood vessel through the stimulation of growth factors and change of cell to cell contact. Because of immunogenicity, autologous EPC therapy is preferable than allograft. However, the number and function of EPCs derived from old and chronic patients are insufficient for successful treatment. In order to retrieve sufficient numbers of EPC from old or chronic patients and restore its function for clinical application, suitable cell preconditioning such as cell stretch, shear stress, and mechanical pressure given by blood flow in vivo may be required before transplantation. Our previous studies have shown that exposure of ECs to mechanical stretch in vitro increased the abilities of migration, proliferation, and tube formation, which could accelerate angiogenesis in impaired tissue. Methods, Results & Conclusion In this study, we explored whether mechanical stretch can improve the survival and proliferation of EPC derived from old or chronic patients by applying cyclic stretch in the range of 5%-15% with use of computerized cell strain system Flexcell-6000. In response to cyclic strain, EPCs increased cell viability, migration and tube formation ability based on matrigel tube assay. Effect of cyclic stretch on the expression of a variety of paracrine factors and extracellular matrix and also their efficacy on vasculogenesis in vivo using limb ischemia model will be estimated.