Background: Due to the multilineage differentiation ability and paracrine role of adipose-derived stem cells (ASCs)\nfor bladder defect repair, various scaffolds have been applied in combination with ASCs to promote bladder\nregeneration and restore bladder function. However, the low survival rate of ASCs and the difficulty of promoting\nbladder functional recovery are still unsolved. To explore these problems, we investigated the feasibility of a novel\nscaffold seeded with ASCs in a rat model of bladder augmentation.\nMethods: A novel autologous myofibroblast (AM)-silk fibroin (SF) scaffold was harvested after subcutaneously\nprefabricating the bladder acellular matrix grafts (BAMG) and SF by removing the BAMG. The AM-SF scaffolds were\nthen seeded with ASCs (AM-SF-ASCs). Fifty percent supratrigonal cystectomies were performed followed by\naugmenting the cystectomized defects with AM-SF scaffolds or AM-SF-ASCs. The histological and functional\nassessments of bladders were performed 2, 4, and 12 weeks after surgery while the ASCs were tracked in vivo.\nResults: For bladder tissue regeneration, immunofluorescence analysis revealed that AM-SF-ASCs (the experimental\ngroup) promoted better morphological regeneration of the urothelium, vessels, bladder smooth muscle, and nerve\nthan AM-SF scaffolds (the control group). Regarding functional restoration, the AM-SF-ASC group exhibited higher\nbladder compliance and relatively normal micturition pattern compared to the AM-SF group. In addition, a certain\nnumber of surviving ASCs could be found in vivo 12 weeks after implantation, and some of them had differentiated\ninto smooth muscle cells.\nConclusions: The AM-SF scaffolds with ASCs could rapidly promote bladder morphological regeneration and\nimproved bladder urinary function. In addition, the bag-shaped structure of the AM-SF scaffold can improve the\nsurvival of ASCs for at least 12 weeks. This strategy of AM-SF-ASCs has a potential to repair large-scale bladder\ndefects in the clinic in the future.
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