Team hopes technique will lead to new approach to repair developmental bladder abnormalities.
Researchers in the U.S. reported on the development of a new technique that uses bone marrow mesenchymal stem cells (MSCs) to partially regenerate bladder tissue in nonhuman primates. They hope their achievement will provide new insights into the bladder-regeneration process in vivo, and ultimately lead to new approaches to correcting developmental bladder abnormalities in pediatric patients. The studies, reported by Arun Sharma, Ph.D., and Earl Cheng, Ph.D., from the Feinberg School of Medicine at Northwestern University, are published in Stem Cells, in a paper titled, A Non-Human Primate Model for Urinary Bladder Regeneration Utilizing Autologous Sources of Bone Marrow Derived Mesenchymal Stem Cells.
Therapeutic approaches to address developmental urinary bladder abnormalities in pediatric patients have to date relied heavily on surgical intervention in the form of bladder-augmentation cystoplasty, Drs. Sharma, Cheng, and colleagues report. However, the technique is beset by drawbacks and can only be considered a stopgap measure. Moreover, they add, clinical attempts to create functional bladder tissue and overcome the problems associated with traditional bladder augmentation have also been met by numerous obstacles. One such technique has used myelomeningocele patient-derived urothelial and bladder smooth muscle cells (bSMCs) to reconstruct the urothelium and smooth muscle components of the bladder. Although highly innovative in approach, the authors admit, “these studies demonstrated lackluster physiological effects and did not address the possibility that the use of pathologic bladder cells may eventually result in the reformation of a diseased bladder state as well as the decline in urodynamic function of patients undergoing this treatment.”
Drs. Sharma and Cheng’s approach instead used bone marrow MSCs that in a clinical setting would be taken from the patient. They found that such cells have both phenotypic and physiological similarities with bSMCs, which they hypothesized could allow the cells to serve as an alternative source of cells for damaged bSMCs.
“For our research we developed a primate-based model, using a baboon bladder in conjunction with bone marrow MSCs to attempt partial bladder regeneration,” Sharma explains. “We found that the mesenchymal stem cells used throughout the study retained the ability to populate a surgically grafted area while remaining active 10 weeks after surgery.”
The researchers hope their approach could provide valuable new insight into the cellular and molecular interactions that govern bladder regeneration. “The newly described bladder-augmentation model represents a unique insight into the bladder-regeneration process and provides strong evidence that MSCs can be exploited for tissue-engineering purposes,” Sharma concludes. “The nonhuman primate bladder-augmentation model established in this study will also further provide key preclinical data that may eventually be translated in a clinical setting.”