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Diabetic Mesenchymal Stem Cells Are Ineffective for Improving Limb Ischemia Due to Their Impaired Angiogenic Capability

 Hyongbum Kim  ;  Ji Woong Han  ;  Ji Yoon Lee  ;  Yong Jin Choi  ;  Young-Doug Sohn  ;  Myungjae Song  ;  Young-sup Yoon 
 CELL TRANSPLANTATION, Vol.24(8) : 1571-1584, 2015 
Journal Title
Issue Date
Animals ; Blood Vessels/physiology ; Capillaries/physiopathology ; Cell Differentiation ; Cell Proliferation ; Coculture Techniques ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology ; Disease Models, Animal ; Endothelial Cells/cytology ; Hindlimb/blood supply ; Hindlimb/metabolism ; Humans ; Ischemia/pathology ; Ischemia/therapy* ; Male ; Mesenchymal Stem Cell Transplantation* ; Mesenchymal Stromal Cells/cytology* ; Mesenchymal Stromal Cells/metabolism ; Neovascularization, Physiologic* ; Proto-Oncogene Proteins c-akt/metabolism ; Rats
Diabetes mellitus ; Mesenchymal stem cells (MSCs) ; Ischemic ; Angiogenesis
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.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Hyongbum(김형범) ORCID logo https://orcid.org/0000-0002-4693-738X
Yoon, Young Sup(윤영섭)
Lee, Ji Yoon(이지윤)
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