Abstract 606: Ischemic Rescue By Transplantation Of Vascular Progenitor Cells Isolated From Fat

Abstract

Background: Peripheral vascular disease remains a leading cause of vascular morbidity and mortality worldwide despite advances in medical and surgical therapy. Besides traditional approaches, which can only restore blood flow to native arteries, an alternative approach is to enhance the growth of new vessels, thereby facilitating the physiological response to ischemia. Methods: Actin CreER /R26 VT2/GK3 “Rainbow” reporter mouse was used for unbiased in vivo survey of injury-responsive vasculogenic clonal formation. Prospective isolation and transplantation were used to determine vessel-forming capacity of different populations. Single-cell RNA sequencing was used to characterize distinct vessel-forming populations and their interactions. Results: Two populations of distinct vascular stem/progenitor cells (VSPCs) were identified from adipose-derived mesenchymal stromal cells (MSCs): VSPC1 is CD45-Ter119-Tie2+PDGFRa-CD31+CD105 high Sca1 low , which gives rise to stunted vessels (incomplete tubular structures) in a transplant setting, and VSPC2 which is CD45-Ter119-Tie2+PDGFRa+CD31-CD105 low Sca1 high and forms stunted vessels and fat. Interestingly, co-transplantation of VSPC1 and VSPC2 is required to form functional vessels that improve perfusion in the mouse hindlimb ischemia model. Similarly, VSPC1 and VSPC2 populations isolated from human adipose tissue could rescue the ischemic condition in mice. Conclusions: These findings suggest that autologous co-transplantation of synergistic VSPCs from non-essential adipose tissue can promote neovascularization and represents a promising treatment for ischemic disease.