RESUMO
Decellularized natural bladder matrices (neobladders) represent an exciting means to regenerate the bladder following bladder cancer-associated cystectomy. In this study, we compare the evolution of decellularized matrices with recellularized matrices by seeding it with human adipose-derived mesenchymal stem cells (ADSC) after implantation following partial cystectomy in rats. We discovered significant anatomical differences since 10 days after neobladder implantation with the ADSC-containing matrices promoting a significant recovery of mature p63- and cytokeratin 7-positive urothelium. We also discovered significantly induced expression of the vimentin mesoderm marker in the submucosal layer in ADSC-seeded matrices. Interestingly, we found a higher expression of smooth muscle actin in transversal and longitudinal smooth muscle layers with ADSC-seeded matrices. Furthermore, ADSC also showed increased vascularization and nerve innervation of the neobladder as determined by the distribution of CD31 and S100ß reactivity, respectively. We believe that ADSC and their paracrine-acting pro-regenerative secretome within decellularized matrices represent an efficient bladder substitution strategy; however, we require a fuller understanding of the mechanisms involved before clinical studies can begin.
RESUMO
Animal experimentation models are a necessary prerequisite to human trials for the use of regenerative medicine in the treatment of spinal cord injuries. Considerable effort is required for the generation of a consistent and reproducible methodology to incur an injury and evaluate the results. The traumatic contusion model has been accepted as a model that closely mimics a typical human traumatic injury, and here we detail step by step an approach to generate a reproducible lesion in rats. Acute cell transplantation by intramedullar or intrathecal administration is described for regenerative interventions. The same model is suitable to design subacute or chronic therapeutic approaches by interventions 1 week or 1 month after lesion.