Adipose-derived stem cells-seeded bladder acellular matrix graft-silk fibroin enhances bladder reconstruction in a rat model
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Dongdong Xiao1,*, Qiong Wang2,*, Hao Yan1, Xiangguo Lv1, Yang Zhao1, Zhe Zhou1, Ming Zhang1, Qian Sun3, Kang Sun3, Wei Li3,** and Mujun Lu1,**
1Department of Urology and Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
2Department of Urology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
3The State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
*These authors contributed equally and are co-first authors of this manuscript
**These authors are co-corresponding authors of this manuscript
Mujun Lu, email: email@example.com
Wei Li, email: firstname.lastname@example.org
Keywords: bladder augmentation, adipose stem cell, silk fibroin, bladder acellular matrix graft, angiogenesis
Received: July 22, 2017 Accepted: August 28, 2017 Published: September 23, 2017
The unfavourable clinical outcomes of host cell-seeded scaffolds for bladder augmentation warrant improved bioactive biomaterials. This study aimed to examine the feasibility of adipose-derived stem cells (ASCs)-seeded bilayer bladder acellular matrix graft (BAMG)-silk fibroin (SF) scaffold in enhancing bladder reconstruction. Sprague Dawley rats were randomly divided into three groups: the BAMG-SF-ASCs group, the acellular BAMG-SF group and the cystotomy group. The BAMG-SF-ASCs group was sampled at 2, 4 and 12 weeks, and compared with the other groups at 12 weeks. In the BAMG-SF-ASCs group, the normal bladder contour was reformed similar to that in the cystotomy group, with abundant urothelium and smooth muscle regeneration, as well as a suitable scaffold degradation speed, and trivial fibrosis and inflammation. The ASCs seeded in BAMG-SF were maintained in the regenerated region during the 12-week experimental period and significantly enhanced the vessel density, nerve regeneration and bladder function compared with acellular BAMG-SF. In addition, the BAMG-SF-ASCs group presented elevated levels of SDF-1α, VEGF and their receptors, with an obvious increase in ERK 1/2 phosphorylation. BAMG-SF is a promising biomaterial for ASCs seeding to facilitate bladder augmentation and demonstrated an enhanced angiogenic potential possibly related to the SDF-1α/CXCR4 pathway via ERK 1/2 activation.
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