The use of stem cell therapy in bladder reconstruction is limited by ineffective scaffolds to convey and sustain stem cells in the desired region. The aims of this study were to evaluate the feasibility of using the bladder acellular matrix grafts-alginate di-aldehyde-gelatine hydrogel-silk mesh (BAMG-HS) composite scaffold encapsulated with adipose-derived stem cells (ASCs) for bladder augmentation and to investigate the potential mechanisms of regeneration.
Male Sprague-Dawley rats (8 weeks old) were randomly assigned to the BAMG-HS-ASCs group (n=18, allocated to 2, 4 and 12 weeks post-operation subgroups, n=6/subgroup), acellular BAMG-HS group (n=6 at 12 weeks post-operation) or cystotomy control group (n=6 at 12 weeks post-operation). At each time point, histological and functional bladder regeneration was evaluated. Quantitative real-time PCR and western blot analyses were performed to probe the angiogenetic potential of ASCs.
Equipped with good cytocompatibility and superior mechanical properties, BAMG-HS acted a tri-layer “sandwich” scaffold with trivial interference in systematic homeostasis. BAMG-HS delivered and sustained ASCs in the initial implantation area for 12 weeks. ASCs in BAMG-HS promoted morphological and histological bladder restoration by accelerating scaffold degradation, ameliorating fibrosis and regulating inflammation. Additionally, ASCs facilitated the recovery of bladder function by enhancing smooth muscle regeneration, innervation and angiogenesis. With the exception of a small number of endothelium-differentiated ASCs that incorporated into the regenerated vessels, the pro-angiogenetic effects of ASCs were associated with the stromal cell-derived factor-1a (SDF-1α)/CXC chemokine receptor 4 (CXCR4) pathway by activating extracellular signal-regulated kinases 1/2 (ERK1/2).
The BAMG-HS composite scaffold is a safe and effective vehicle for encapsulating ASCs that promotes bladder histological regeneration and functional restoration via SDF-1α/CXCR4 pathway with clinical applications potential.