1. A Combination of Distinct Vascular Stem/Progenitor Cells for Neovascularization and Ischemic Rescue.
- Author
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Zhao, Liming, Lee, Andrew S, Sasagawa, Koki, Sokol, Jan, Wang, Yuting, Ransom, Ryan C, Zhao, Xin, Ma, Chao, Steininger, Holly M, Koepke, Lauren S, Borrelli, Mimi R, Brewer, Rachel E, Lee, Lorene LY, Huang, Xianxi, Ambrosi, Thomas H, Sinha, Rahul, Hoover, Malachia Y, Seita, Jun, Weissman, Irving L, Wu, Joseph C, Wan, Derrick C, Xiao, Jun, Longaker, Michael T, Nguyen, Patricia K, and Chan, Charles KF
- Subjects
Adipose Tissue ,Mesenchymal Stem Cells ,Hindlimb ,Animals ,Humans ,Mice ,Ischemia ,Disease Models ,Animal ,Neovascularization ,Pathologic ,Neovascularization ,Physiologic ,adipose tissue ,angiogenesis ,hindlimb ischemia ,mesenchymal stem cells ,neovascularization ,peripheral vascular disease ,stem cells ,Regenerative Medicine ,Stem Cell Research - Nonembryonic - Non-Human ,Stem Cell Research ,Biotechnology ,Transplantation ,2.1 Biological and endogenous factors ,Aetiology ,Cardiovascular ,Good Health and Well Being ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Cardiovascular System & Hematology - Abstract
BackgroundPeripheral 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.MethodsThe ActinCreER/R26VT2/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.ResultsTwo populations of distinct vascular stem/progenitor cells (VSPCs) were identified from adipose-derived mesenchymal stromal cells: VSPC1 is CD45-Ter119-Tie2+PDGFRa-CD31+CD105highSca1low, which gives rise to stunted vessels (incomplete tubular structures) in a transplant setting, and VSPC2 which is CD45-Ter119-Tie2+PDGFRa+CD31-CD105lowSca1high and forms stunted vessels and fat. Interestingly, cotransplantation 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.ConclusionsThese findings suggest that autologous cotransplantation of synergistic VSPCs from nonessential adipose tissue can promote neovascularization and represents a promising treatment for ischemic disease.
- Published
- 2023