title: G-CSF-mobilized peripheral blood mononuclear cells from diabetic patients augment neovascularization in ischemic limbs but with impaired capability.
abstract: BACKGROUND
  Autologous transplantation of mobilized peripheral blood mononuclear cells (M-PBMNCs) is a novel approach to improve critical limb ischemia (CLI) in diabetes. However, endothelial progenitor cells (EPCs) from diabetes are dysfunctional and impaired in ischemia-induced neovascularization.
  
  
  OBJECTIVE
  This study aimed to confirm the compromised efficiency of diabetic M-PBMNCs in therapeutic neovascularization, and to determine the underlying mechanisms of this impairment.
  
  
  METHODS
  Diabetic M-PBMNCs from 17 diabetic patients or healthy controls, or phosphate-buffered saline (PBS) were injected into the ischemic limbs of streptozotocin-induced diabetic nude mice. The limb blood perfusion, ambulatory score, ischemia damage, capillary/fiber ratio, arteriole density, collateral vessel formation, and pericytes recruitment were evaluated between these three groups. Non-invasive real time image and histopathology were used to detect the in vivo role of transplanted M-PBMNCs. Proliferation and adhesion of EPCs were assayed. In vitro vascular network incorporation and matrigel plug assay were used to test the pro-neovascularization role of M-PBMNCs.
  
  
  RESULTS
  Transplantation of diabetic M-PBMNCs also improved neovascularization, but to a lesser extent from that observed with non-diabetic ones. This was associated with the impairment of diabetic M-PBMNCs capacity to differentiate into EPCs, to incorporate into vessel-like tubules in vitro, to participate in vascular-like structure formation in a subcutaneous matrigel plug, and to stimulate the recruitment of pericytes/smooth muscle cells. In addition, there was impairment in vasculogenesis, which was related to the reduced adhesion ability of EPCs from diabetic M-PBMNCs.
  
  
  CONCLUSIONS
  Diabetes reduced the capacity of M-PBMNCs to augment neovascularization in ischemia.
authors.affiliation: State Key Laboratory of Experimental Hematology, National Research Center for Stem Cell Engineering and Technology, Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.
authors.forename: B
authors.initials: B
authors.lastname: Zhou
authors.forename: Y Y
authors.initials: YY
authors.lastname: Bi
authors.forename: Z B
authors.initials: ZB
authors.lastname: Han
authors.forename: H
authors.initials: H
authors.lastname: Ren
authors.forename: Z H
authors.initials: ZH
authors.lastname: Fang
authors.forename: X F
authors.initials: XF
authors.lastname: Yu
authors.forename: M-C
authors.initials: MC
authors.lastname: Poon
authors.forename: Z C
authors.initials: ZC
authors.lastname: Han
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D017690:Cell Transplantation; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology*; D005121:Extremities / Q000098:blood supply*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007511:Ischemia / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects*; D018919:Neovascularization, Physiologic
chemical_list: D016179:Granulocyte Colony-Stimulating Factor