TY - JOUR
T1 - The effect of urine-derived stem cells expressing VEGF loaded in collagen hydrogels on myogenesis and innervation following after subcutaneous implantation in nude mice
AU - Liu, Guihua
AU - Wang, Xisheng
AU - Sun, Xiangzhou
AU - Deng, Chunhua
AU - Atala, Anthony
AU - Zhang, Yuanyuan
PY - 2013/11/1
Y1 - 2013/11/1
N2 - Impairment of sphincter muscles or their neural and vascular support leads to stress urinary incontinence. The aim of this study was to determine the role of urine-derived stem cells (USCs) over-expressing vascular endothelial growth factor (VEGF) in collagen-I gel on angiogenesis, cell survival, cell growth, myogenic phenotype differentiation of the implanted cells and innervations following implantation invivo. USCs were infected with adenovirus containing the human VEGF165 and green fluorescent protein genes. A total of 5×106 cells, USCs alone, or plus endothelial cells or human skeletal myoblasts (as control) suspended in collagen-I gel were subcutaneously implanted into nude mice. Extensive vascularization and more implanted cells was noted in VEGF-expressing USCs groups compared to the non-VEGF groups invivo. Numbers of the cells displaying endothelial markers (CD 31 and von Willebrand's factor) and myogenic markers (myf-5, MyoD and desmin), and regenerated nerve fibers displaying neural markers (S-100, GFAP and neurofilament) significantly increased in the grafts of VEGF-expressing USCs. Improved angiogenesis by VEGF-expressing USCs enhanced grafted cell survival, recruited the resident cells and promoted myogenic phenotype differentiation of USCs and innervation. This approach has important clinical implications for the development of cell therapies for the correction of stress urinary incontinence.
AB - Impairment of sphincter muscles or their neural and vascular support leads to stress urinary incontinence. The aim of this study was to determine the role of urine-derived stem cells (USCs) over-expressing vascular endothelial growth factor (VEGF) in collagen-I gel on angiogenesis, cell survival, cell growth, myogenic phenotype differentiation of the implanted cells and innervations following implantation invivo. USCs were infected with adenovirus containing the human VEGF165 and green fluorescent protein genes. A total of 5×106 cells, USCs alone, or plus endothelial cells or human skeletal myoblasts (as control) suspended in collagen-I gel were subcutaneously implanted into nude mice. Extensive vascularization and more implanted cells was noted in VEGF-expressing USCs groups compared to the non-VEGF groups invivo. Numbers of the cells displaying endothelial markers (CD 31 and von Willebrand's factor) and myogenic markers (myf-5, MyoD and desmin), and regenerated nerve fibers displaying neural markers (S-100, GFAP and neurofilament) significantly increased in the grafts of VEGF-expressing USCs. Improved angiogenesis by VEGF-expressing USCs enhanced grafted cell survival, recruited the resident cells and promoted myogenic phenotype differentiation of USCs and innervation. This approach has important clinical implications for the development of cell therapies for the correction of stress urinary incontinence.
KW - Cell therapy
KW - Stress urinary incontinence (SUI)
KW - Urine-derived stem cells (USCs)
KW - Vascular endothelial growth factor (VEGF)
UR - http://www.scopus.com/inward/record.url?scp=84882890381&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84882890381&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2013.07.077
DO - 10.1016/j.biomaterials.2013.07.077
M3 - Article
C2 - 23932297
AN - SCOPUS:84882890381
VL - 34
SP - 8617
EP - 8629
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
IS - 34
ER -