title: Diabetic Mesenchymal Stem Cells Are Ineffective for Improving Limb Ischemia Due to Their Impaired Angiogenic Capability.
abstract: The purpose of this study was to investigate the effects of diabetes on mesenchymal stem cells (MSCs) in terms of their angiogenic and therapeutic potential for repairing tissue ischemia. We culture-isolated MSCs from streptozotocin-induced diabetic rats (D-MSCs) and compared their proliferation, differentiation, and angiogenic effects with those from normal rats (N-MSCs). The angiogenic effects of MSCs were evaluated by real-time PCR, in vitro tube formation assay, and transplantation of the MSCs into a hindlimb ischemia model followed by laser Doppler perfusion imaging. The number of MSCs derived from diabetic rats was smaller, and their proliferation rate was slower than N-MSCs. Upon induction of differentiation, the osteogenic and angiogenic differentiation of D-MSCs were aberrant compared to N-MSCs. The expression of angiogenic factors was lower in D-MSCs than N-MSCs. D-MSCs cocultured with endothelial cells resulted in decreased tube formation compared to N-MSCs. D-MSCs were ineffective to improve hindlimb ischemia and showed lower capillary density and angiogenic gene expression in ischemic limbs than N-MSCs. D-MSCs have defective proliferation and angiogenic activities and are ineffective for repairing hindlimb ischemia. Newer measures are needed before MSCs can be employed as a source for autologous cell therapy.
authors.affiliation: Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Hyongbum
authors.initials: H
authors.lastname: Kim
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Han
authors.forename: Ji Yoon
authors.initials: JY
authors.lastname: Lee
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Choi
authors.forename: Young-Doug
authors.initials: YD
authors.lastname: Sohn
authors.forename: Myungjae
authors.initials: M
authors.lastname: Song
authors.forename: Young-sup
authors.initials: YS
authors.lastname: Yoon
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000502:physiology; D002196:Capillaries / Q000503:physiopathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology; D006614:Hindlimb / Q000098:blood supply / Q000378:metabolism; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D018919:Neovascularization, Physiologic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats
chemical_list: C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt