VEGF gene transfected umbilical cord mesenchymal stem cells transplantation improve the lower limb vascular lesions of diabetic rats

被引:24
作者
Li, Xiaoling [1 ]
Gan, Kexin [2 ]
Song, Guangyao [1 ]
Wang, Chao [2 ]
机构
[1] Hebei Med Univ, Dept Internal Med, Shijiazhuang 050017, Hebei Province, Peoples R China
[2] Hebei Gen Hosp, Dept Endocrinol, Shijiazhuang, Hebei, Peoples R China
关键词
Diabetes; Stem cells; VEGF; Lower limb vascular lesion; Transplantation; INSULIN-PRODUCING CELLS; FOOT ULCERS; MARROW; MICE; GENERATION; MURINE; TISSUE; ANGIOGENESIS; THERAPY; DISEASE;
D O I
10.1016/j.jdiacomp.2015.04.018
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Previous studies had explored the therapeutic effect of hUC-MSCs transplantation on ischemia; in this study, we further assessed the effectiveness of VEGF over-expressed hUC-MSCs cells transplantation on vascular proliferation in lower limb ischemia model in type 2 diabetic rats. Methods: hUC-MSCs cells were over-expressed with VEGF, and transplanted to lower limb ischemia rats model of type 2 diabetes. Results: VEGF over-expression increased the hUC-MSCs cells proliferation activity and VEGF secretion. VEGF gene transfected hUC-MSCs transplantation increased VEGF expression at a high level throughout 4 weeks in skeletal muscle tissues of rats. Importantly, the vascular proliferation and blood perfusion of VEGF over-expressed hUC-MSCs transplanted limb were significantly improved compared with those of control group. The expression levels of ERK, AKT, MMP2 and MMP9 in VEGF over-expressed hUC-MSCs transplantation group increased dramatically compared with control group, while TIMP1 and TIMP2 expression had no significant change. Conclusion: VEGF over-expressed hUC-MSCs transplantation was more effective to stimulate angiogenesis and increase blood perfusion than the simply hUC-MSCs transplantation, as maybe a new choice to improve the lower limb vascular lesions of diabetics. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:872 / 881
页数:10
相关论文
共 32 条
[1]  
Ala A., 2011, GLOBAL STATUS REPORT, P9
[2]   Practical guidelines on the management and prevention of the diabetic foot - Based upon the International Consensus on the Diabetic Foot (2007) prepared by the International Working Group on the Diabetic Foot [J].
Apelqvist, J. ;
Bakker, K. ;
van Houtum, W. H. ;
Schaper, N. C. .
DIABETES-METABOLISM RESEARCH AND REVIEWS, 2008, 24 :S181-S187
[3]   The global burden of diabetic foot disease [J].
Boulton, AJM ;
Vileikyte, L ;
Ragnarson-Tennvall, G ;
Apelqvist, J .
LANCET, 2005, 366 (9498) :1719-1724
[4]   Neuropathic diabetic foot ulcers [J].
Boulton, AJM ;
Kirsner, RS ;
Vileikyte, L .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (01) :48-55
[5]  
Bowering CK, 2001, CAN FAM PHYSICIAN, V47, P1007
[6]   Targeting Nonhealing Ulcers of Lower Extremity in Human Through Autologous Bone Marrow-Derived Mesenchymal Stem Cells [J].
Dash, Nihar Ranjan ;
Dash, Surjya Narayan ;
Routray, Padmanav ;
Mohapatra, Sribatsha ;
Mohapatra, Prakash C. .
REJUVENATION RESEARCH, 2009, 12 (05) :359-366
[7]   Towards Reaching the Target: Clinical Application of Mesenchymal Stem Cells for Diabetic Foot Ulcers [J].
Dash, Surjya Narayan ;
Dash, Nihar Ranjan ;
Guru, Bhikaricharan ;
Mohapatra, Prakash Chandra .
REJUVENATION RESEARCH, 2014, 17 (01) :40-53
[8]   Enhanced Healing of Diabetic Wounds by Topical Administration of Adipose Tissue-Derived Stromal Cells Overexpressing Stromal-Derived Factor-1: Biodistribution and Engraftment Analysis by Bioluminescent Imaging [J].
Di Rocco, Giuliana ;
Gentile, Antonietta ;
Antonini, Annalisa ;
Ceradini, Francesca ;
Wu, Joseph C. ;
Capogrossi, Maurizio C. ;
Toietta, Gabriele .
STEM CELLS INTERNATIONAL, 2011, 2011
[9]   Mesenchymal Stem-Cell Immunosuppressive Capabilities: Therapeutic Implications in Islet Transplantation [J].
Ding, Yunchuan ;
Bushell, Andrew ;
Wood, Kathryn J. .
TRANSPLANTATION, 2010, 89 (03) :270-273
[10]   Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds [J].
Falanga, Vincent ;
Iwamoto, Satori ;
Chartier, Molly ;
Yufit, Tatyana ;
Butmarc, Janet ;
Kouttab, Nicholas ;
Shrayer, David ;
Carson, Polly .
TISSUE ENGINEERING, 2007, 13 (06) :1299-1312