Human adipose-derived mesenchymal stem cells accelerate decellularized neobladder regeneration

Autores de CIPF

• 

  M Victoria Moreno Manzano

  Autor

• 

  Maravillas Mellado López

  Autor

• Ana Alastrue Agudo

  Autor

• Viviana Bisbal Velasco

  Autor

• Jerónimo Forteza Vila

  Autor

Participantes ajenos a CIPF

• Morera-Esteve, MJ
• Serrano-Aroca, A
• Vera-Donoso, CD

Grupos de Investigación

• Laboratorio de Regeneración Tisular y Neuronal

  

  Jefe/a de Grupo

  M Victoria Moreno Manzano

Abstract

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 S100 beta 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.

Keywords

• mesenchymal stem cells; bladder regeneration; decellularized matrices; neobladder