title: Multipotent vasculogenic pericytes from human pluripotent stem cells promote recovery of murine ischemic limb.
abstract: BACKGROUND
  Pericytes represent a unique subtype of microvessel-residing perivascular cells with diverse angiogenic functions and multilineage developmental features of mesenchymal stem cells. Although various protocols for derivation of endothelial and/or smooth muscle cells from human pluripotent stem cells (hPSC, either embryonic or induced) have been described, the emergence of pericytes in the course of hPSC maturation has not yet been elucidated.
  
  
  RESULTS
  We found that during hPSC development, spontaneously differentiating embryoid bodies give rise to CD105(+)CD90(+)CD73(+)CD31(-) multipotent clonogenic mesodermal precursors, which can be isolated and efficiently expanded. Isolated and propagated cells expressed characteristic pericytic markers, including CD146, NG2, and platelet-derived growth factor receptor β, but not the smooth muscle cell marker α-smooth muscle actin. Coimplantation of hPSC-derived endothelial cells with pericytes resulted in functional and rapid anastomosis to the murine vasculature. Administration of pericytes into immunodeficient mice with limb ischemia promoted significant vascular and muscle regeneration. At day 21 after transplantation, recruited hPSC pericytes were found incorporated into recovered muscle and vasculature.
  
  
  CONCLUSIONS
  Derivation of vasculogenic and multipotent pericytes from hPSC can be used for the development of vasculogenic models using multiple vasculogenic cell types for basic research and drug screening and can contribute to angiogenic regenerative medicine.
authors.affiliation: Department of Ob-Gyn, Rambam Health Care Campus, Haifa 31096, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Dar
authors.forename: Hagit
authors.initials: H
authors.lastname: Domev
authors.forename: Oren
authors.initials: O
authors.lastname: Ben-Yosef
authors.forename: Maty
authors.initials: M
authors.lastname: Tzukerman
authors.forename: Naama
authors.initials: N
authors.lastname: Zeevi-Levin
authors.forename: Atara
authors.initials: A
authors.lastname: Novak
authors.forename: Igal
authors.initials: I
authors.lastname: Germanguz
authors.forename: Michal
authors.initials: M
authors.lastname: Amit
authors.forename: Joseph
authors.initials: J
authors.lastname: Itskovitz-Eldor
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000637:transplantation; D005121:Extremities / Q000098:blood supply* / Q000601:surgery; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000601:surgery*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D039902:Multipotent Stem Cells / Q000637:transplantation*; D020286:Pericytes / Q000637:transplantation*; D039904:Pluripotent Stem Cells / Q000637:transplantation*; D020127:Recovery of Function / Q000502:physiology*