Autologous Smooth Muscle Progenitor Cells Enhance Regeneration of Tissue-Engineered Bladder

Tissue engineering techniques provide a great potential to de novo construct a histological bladder. Smooth muscle regeneration is extremely important for the functional recovery of engineered neobladder. However, many challenges remain for the use of bladder smooth muscle cells (SMCs) as the cell sources. Recent evidences showed that smooth muscle progenitor cells (SPCs) in the peripheral blood have the capacity of differentiating into SMCs, while their use for bladder regeneration has not yet been reported. The aim of our study was to investigate the effect and mechanism of autologous SPCs on bladder regeneration in a rabbit model. In this study, autologous SPCs were isolated and cultured from the peripheral blood, labeled with CM-DiI, and then seeded into a porcine bladder acellular matrix (BAM) to construct a SPC-BAM complex, which was finally implanted to substitute the partial bladder with an equivalent size. In the results, SPCs demonstrated the phenotype of stem/progenitor cells, expressed SMs markers (alpha-smooth muscle actin [α-SMA], desmin, calponin, SM22α, and smooth muscle myosin heavy chain [SMMHC]), and displayed carbachol-induced contraction. Compared with cell-free BAM, the SPC-BAM was able to improve histological regeneration (smooth muscle regeneration, vascularization, and nerve formation) and functional recovery (urodynamic function and smooth muscle contraction) of the engineered neobladder. Cell tracing indicated that seeded SPCs could survive and directly integrated into the regenerated neobladder. In addition, SPCs could also promote proliferation and migration of rabbit bladder SMCs through the paracrine platelet-derived growth factor-BB (PDGF-BB). In conclusion, our study first demonstrated that SPCs from the peripheral blood could enhance histological regeneration and functional recovery of the tissue-engineered neobladder through both the direct integration and indirect paracrine effect, supporting the use of SPCs as the cell sources for tissue engineering of the bladder.