A Combination of Distinct Vascular Stem/Progenitor Cells for Neovascularization and Ischemic Rescue.

Autor: Zhao L; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Surgery, Division of Plastic and Reconstructive Surgery (L.Z., Y.W., R.C.R., C.M., H.M.S., L.S.K., M.R.B., L.L.Y.L., T.H.A., D.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (L.Z., Y.W., J.X.)., Lee AS; School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, China (A.S.L.).; Institute for Cancer Research, Shenzhen Bay Laboratory, China (A.S.L.)., Sasagawa K; Stanford Cardiovascular Institute (K.S., J.S., X.Z., X.H., J.C.W., M.T.L., P.K.N., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Medicine, Division of Cardiovascular Medicine (K.S., J.S., X.Z., X.H., J.C.W., P.K.N.), Stanford University School of Medicine, CA., Sokol J; Stanford Cardiovascular Institute (K.S., J.S., X.Z., X.H., J.C.W., M.T.L., P.K.N., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Medicine, Division of Cardiovascular Medicine (K.S., J.S., X.Z., X.H., J.C.W., P.K.N.), Stanford University School of Medicine, CA.; Center for Integrative Medical Sciences and Advanced Data Science Project, RIKEN, Tokyo, Japan (J.S.)., Wang Y; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Surgery, Division of Plastic and Reconstructive Surgery (L.Z., Y.W., R.C.R., C.M., H.M.S., L.S.K., M.R.B., L.L.Y.L., T.H.A., D.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (L.Z., Y.W., J.X.)., Ransom RC; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Surgery, Division of Plastic and Reconstructive Surgery (L.Z., Y.W., R.C.R., C.M., H.M.S., L.S.K., M.R.B., L.L.Y.L., T.H.A., D.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA., Zhao X; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Stanford Cardiovascular Institute (K.S., J.S., X.Z., X.H., J.C.W., M.T.L., P.K.N., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Medicine, Division of Cardiovascular Medicine (K.S., J.S., X.Z., X.H., J.C.W., P.K.N.), Stanford University School of Medicine, CA., Ma C; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Surgery, Division of Plastic and Reconstructive Surgery (L.Z., Y.W., R.C.R., C.M., H.M.S., L.S.K., M.R.B., L.L.Y.L., T.H.A., D.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA., Steininger HM; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Surgery, Division of Plastic and Reconstructive Surgery (L.Z., Y.W., R.C.R., C.M., H.M.S., L.S.K., M.R.B., L.L.Y.L., T.H.A., D.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA., Koepke LS; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Surgery, Division of Plastic and Reconstructive Surgery (L.Z., Y.W., R.C.R., C.M., H.M.S., L.S.K., M.R.B., L.L.Y.L., T.H.A., D.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA., Borrelli MR; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA., Brewer RE; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA., Lee LLY; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Surgery, Division of Plastic and Reconstructive Surgery (L.Z., Y.W., R.C.R., C.M., H.M.S., L.S.K., M.R.B., L.L.Y.L., T.H.A., D.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA., Huang X; Stanford Cardiovascular Institute (K.S., J.S., X.Z., X.H., J.C.W., M.T.L., P.K.N., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Medicine, Division of Cardiovascular Medicine (K.S., J.S., X.Z., X.H., J.C.W., P.K.N.), Stanford University School of Medicine, CA., Ambrosi TH; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Surgery, Division of Plastic and Reconstructive Surgery (L.Z., Y.W., R.C.R., C.M., H.M.S., L.S.K., M.R.B., L.L.Y.L., T.H.A., D.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA., Sinha R; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA., Hoover MY; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA., Seita J, Weissman IL; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Developmental Biology (I.L.W., C.K.F.C.), Stanford University School of Medicine, CA., Wu JC; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Stanford Cardiovascular Institute (K.S., J.S., X.Z., X.H., J.C.W., M.T.L., P.K.N., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Medicine, Division of Cardiovascular Medicine (K.S., J.S., X.Z., X.H., J.C.W., P.K.N.), Stanford University School of Medicine, CA., Wan DC; Department of Surgery, Division of Plastic and Reconstructive Surgery (L.Z., Y.W., R.C.R., C.M., H.M.S., L.S.K., M.R.B., L.L.Y.L., T.H.A., D.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA., Xiao J; Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (L.Z., Y.W., J.X.)., Longaker MT; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Surgery, Division of Plastic and Reconstructive Surgery (L.Z., Y.W., R.C.R., C.M., H.M.S., L.S.K., M.R.B., L.L.Y.L., T.H.A., D.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA., Nguyen PK; Stanford Cardiovascular Institute (K.S., J.S., X.Z., X.H., J.C.W., M.T.L., P.K.N., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Medicine, Division of Cardiovascular Medicine (K.S., J.S., X.Z., X.H., J.C.W., P.K.N.), Stanford University School of Medicine, CA., Chan CKF; Institute for Stem Cell Biology and Regenerative Medicine (L.Z., Y.W., R.C.R., X.Z., C.M., H.M.S., L.S.K., M.R.B., R.E.B., L.Y.L., T.H.A., R.S., M.Y.H., I.L.W., J.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Surgery, Division of Plastic and Reconstructive Surgery (L.Z., Y.W., R.C.R., C.M., H.M.S., L.S.K., M.R.B., L.L.Y.L., T.H.A., D.C.W., M.T.L., C.K.F.C.), Stanford University School of Medicine, CA.; Department of Developmental Biology (I.L.W., C.K.F.C.), Stanford University School of Medicine, CA.
Jazyk: angličtina
Zdroj: Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2023 Jul; Vol. 43 (7), pp. 1262-1277. Date of Electronic Publication: 2023 Apr 13.
DOI: 10.1161/ATVBAHA.122.317943
Abstrakt: 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: The 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: 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, 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.
Conclusions: These findings suggest that autologous cotransplantation of synergistic VSPCs from nonessential adipose tissue can promote neovascularization and represents a promising treatment for ischemic disease.
Competing Interests: Disclosures None.
Databáze: MEDLINE