title: Pro-angiogenic efficacy of transplanting endothelial progenitor cells for treating hindlimb ischemia in hyperglycemic rabbits.
abstract: OBJECTIVE
  To evaluate the effectiveness of endothelial progenitor cells (EPCs) therapy in ischemia with or without hyperglycemia.
  
  
  METHODS
  Japanese White Rabbits were randomly assigned to three groups, group SH, hyperglycemia with sham therapy (n=10); group NE, normoglycemia with autologous EPCs transplantation therapy (n=12); and group HE, hyperglycemia with autologous EPCs transplantation therapy (n=12). Hyperglycemia was induced by injecting alloxan and sustained for 12weeks. Hindlimb ischemia was induced by complete excision of the femoral artery. Ex vivo-expanded EPCs were derived from autologous bone marrow and transplanted intermuscularily in the ischemic hindlimb. Fourteen days after transplantation, the indicators were determined.
  
  
  RESULTS
  There is no difference of the functions of ex vivo-expanded EPCs from autologous bone marrow between normoglycemic and hyperglycemic groups. We found significant improvement in both EPCs transplantation therapy groups compared to sham, in terms of the angiogenesis index (8.62±1.36, 11.12±2.23, 12.35±2.97), capillary density (7.06±0.91, 13.51±1.16, 13.90±2.78), capillary to muscle fiber ratio (0.68±0.09, 0.96±0.11,0.89±0.10), muscle VEGF expression (0.22±0.07, 0.41±0.08, 0.38±0.07ng/g). We found no significant differences between hyperglycemic and normoglycemic EPCs therapy groups except for 5 pro-angiogenic genes that were upregulated in HE as compared to NE.
  
  
  CONCLUSIONS
  Ex vivo expanded EPCs from autologous bone marrow transplantation is an effective therapeutic method for hindlimb ischemia in rabbits regardless of glycemic state.
authors.affiliation: Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. Electronic address: chinaqiangli@hotmail.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Daqing People's Hospital, the Fifth Affiliated Hospital of Harbin Medical University, Daqing 163316, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
authors.forename: Jinchao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Geriatrics Research Education and Clinical Center, Miami Veterans Affairs Healthcare System, Miami, FL 33125, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Seldeen
authors.affiliation: Geriatrics Research Education and Clinical Center, Miami Veterans Affairs Healthcare System, Miami, FL 33125, USA.
authors.forename: Manhui
authors.initials: M
authors.lastname: Pang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000637:transplantation*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006614:Hindlimb / Q000098:blood supply*; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D012039:Regional Blood Flow / Q000502:physiology; D016896:Treatment Outcome
keywords: EPCs; Hindlimb ischemia; Hyperglycemia; Neovascularization; Transplantation