Congenital disorders, cancer, trauma, infection, inflammation, iatrogenic injuries or any other condition of the genitourinary system can lead to bladder damage. Most of these situations require eventual reconstructive procedures. In addition to individual cell replacement applications, in recent years, tissue engineering has successfully progressed to contribute to cover the demand of tissue and even organs transplantations. In this regard, the use of decellularized natural matrices to recover a functional organ have been shown to be the most appropriate and powerful source to reconstruct complex biological structures. Such matrices retain chemical and biological cues, while showing similar composition and microstructure as the native tissue. These properties are crucial for tissue engineering approaches, making the decellularized matrices a more physiological environment for the target cells but full of chances and clinical challenges.
All experimental procedures were performed into consideration the ethical processes described by the animal committee of CIPF. Sprague-Dawley rats were used for the experiment. Here we compared the efficient and functional integration of a recellularized acellular matrix, previously seeded in vitro with human adipose tissue derived mesenchymal stem cells with a non-recelullarized matrix. In a rat model of partial cystectomy and bladder substitution.
Relevant and significant anatomical differences were found few days after neo bladders implantation. The human ADSC containing matrix showed a significant recovery of mature urothelium measured as the positive reactivity to p63 at the transitional epithelium layers. The expression of the mesoderm marker, cytokeratin 7 was also significantly induced within the regenerated connective tissue. Interestingly a higher expression of smooth muscle actin was found at both, the internal and peripheral transversal and longitudinal smooth muscle layers in the hADSC-recellularized matrix. However, no significant induction in any of the transplanted groups, in comparison with native bladder, was found for CD31 expression, endothelium marker. The presence of the hADSC, by most probably the paracrine release of pro-regenerative factors, favors a faster and more efficient endogenous regeneration of the ectopic bladder allowing a faster voluntary urodynamic recovery within a more specialized an mature tissue.
Although bladder recellularization and urodynamic functional recovery have been successfully tested in small animals, and here we show the relevant benefits of the use of human ADSC on this regeneration process, more efficient procedures ex-vivo with a better understanding of the mechanisms involved of the ectopic transplanted cells is required in order to improve the tissue maturation in terms of peripheral nerve innervation and vascularization for a proper clinical translation.