TY - JOUR
T1 - Unsorted human adipose tissue-derived stem cells promote angiogenesis and myogenesis in murine ischemic hindlimb model
AU - Kang, Yujung
AU - Park, Chan
AU - Kim, Daham
AU - Seong, Chu Myong
AU - Kwon, Kihwan
AU - Choi, Chulhee
N1 - Funding Information:
This work was supported by Mid-career Researcher Program through NRF grant funded by the MEST (KOSEF, MEST; No. 2009-0080280 ) and the Korea Research Foundation Grant (MOEHRD, Basic Research Promotion Fund, KRF-2006-311-E00056 ), funded by the Korean government.
PY - 2010/12
Y1 - 2010/12
N2 - We examined the protective effect of unsorted human adipose tissue-derived stem cells (hADSCs) with a short-term culture in endothelial differentiation medium on tissue repair after ischemic injury. hADSCs were isolated from human subcutaneous adipose tissue and cultured in vitro in endothelial differentiation medium for 2. wks before transplantation. Cultured hADSCs showed a typical mesenchymal stromal cell-like phenotype, positive for endothelial-specific markers including VE-cadherin, Flt-1, eNOS, and vWF but not CD31. Two hours after ligation of the femoral artery and vein, mice were injected with the unselected hADSCs locally near the surgery site and tested for tissue perfusion and repair. Tissue perfusion rates of the ischemic limbs were significantly higher in the group treated with hADSCs compared with those of the control mice as early as post-operative day 3 (median 195.3%/min; interquartile range, 82.0-321.1 vs. median 47.1%/min; interquartile range, 18.0-58.7; p= 0.001 by Friedman two-way analysis). Subsequently, the mice treated with hADSC showed better prognosis at 4. wks after surgery, and the histological analysis revealed increased vascular density and reduced muscle atrophy in the hADSC-transplanted limbs. Moreover, hADSC-treated muscle contained differentiated myocytes positive for human NF-ΚB and myogenin antigen. These results collectively indicate that unsorted hADSCs after a 2-wk-in vitro culture have a therapeutic potential in ischemic tissue injury via inducing both angiogenesis and myogenesis.
AB - We examined the protective effect of unsorted human adipose tissue-derived stem cells (hADSCs) with a short-term culture in endothelial differentiation medium on tissue repair after ischemic injury. hADSCs were isolated from human subcutaneous adipose tissue and cultured in vitro in endothelial differentiation medium for 2. wks before transplantation. Cultured hADSCs showed a typical mesenchymal stromal cell-like phenotype, positive for endothelial-specific markers including VE-cadherin, Flt-1, eNOS, and vWF but not CD31. Two hours after ligation of the femoral artery and vein, mice were injected with the unselected hADSCs locally near the surgery site and tested for tissue perfusion and repair. Tissue perfusion rates of the ischemic limbs were significantly higher in the group treated with hADSCs compared with those of the control mice as early as post-operative day 3 (median 195.3%/min; interquartile range, 82.0-321.1 vs. median 47.1%/min; interquartile range, 18.0-58.7; p= 0.001 by Friedman two-way analysis). Subsequently, the mice treated with hADSC showed better prognosis at 4. wks after surgery, and the histological analysis revealed increased vascular density and reduced muscle atrophy in the hADSC-transplanted limbs. Moreover, hADSC-treated muscle contained differentiated myocytes positive for human NF-ΚB and myogenin antigen. These results collectively indicate that unsorted hADSCs after a 2-wk-in vitro culture have a therapeutic potential in ischemic tissue injury via inducing both angiogenesis and myogenesis.
KW - Angiogenesis
KW - Cell differentiation
KW - Endothelial cell
KW - Image-based flow modeling
KW - Perfusion
KW - Peripheral vascular diseases
KW - Stem cells
UR - http://www.scopus.com/inward/record.url?scp=78249280990&partnerID=8YFLogxK
U2 - 10.1016/j.mvr.2010.05.006
DO - 10.1016/j.mvr.2010.05.006
M3 - Article
C2 - 20510252
AN - SCOPUS:78249280990
VL - 80
SP - 310
EP - 316
JO - Microvascular Research
JF - Microvascular Research
SN - 0026-2862
IS - 3
ER -