to differentiate stem cells into specialized tissue without the use of a dedicated matrix or scaffold and without cell contact of any kind.
Developing stem cells into a viable treatment for bladder dysfunction eliminates some of the disadvantages of current methods. These treatments can eliminate invasive surgery like augmentation cystoplasty and the complications that could arise. Using a patient’s own cells for therapy eliminates the risk of immunologic rejection.
Human stem cells do need further testing before they can become a viable therapy. The differentiated cell products need to be completely pure, adult, differentiated cells without pluripotent cells that could cause issues when transplanted. To become a reliable therapy, the growth conditions and methods for differentiating stem cells needs to be consistent and replicable. The signals that cause differentiation need to be elucidated and the microenvironment needs to be well defined.
Beyond the Boundaries of Urothelial Stem Cell Differentiation
The scope of current studies is to relieve the complications of bowel resection and broaden the scope of regeneration of bladder tissue for all kinds of bladder pathologies. A healthy side-effect of discovering methods to differentiate hESCs, iPSCs, and MSCs into viable, healthy, lasting bladder cells is more than just the ability for replacing tissues and organs.
When researching the methods and proper signals needed to differentiate those pluripotent cells, scientists believe there is also potential to learn about the pathways that cause such diseases or malformations. Scientists speculate that this could lead to a greater understanding of the signals, cell components, and microenvironment that are responsible for bladder pathology and self-repair processes. There has also been suggestion that the bladder cell lines created, as a renewable, reliable source of in vitro cell models, could be a useful tool to test drug toxicity and clinical therapies before transition to animal models. These cell lines that are created can also be used to study cancer pathways and treatment targets. In addition, ongoing studies in bladder regenerative research increases the likelihood of successful strategies for other types of tissue and regenerative medical therapies.
Stem Cells Showing Promise in Regenerative Therapy of the Bladder
Human embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells are all potential sources of adult differentiated bladder cells. Grafts, scaffolds, and new cells need to be scaled up to a small animal model and then a larger animal model before use in human clinical trials. The methods of using stem cells for augmenting damaged tissue or full organ replacement need to be proven to avoid sudden cell death after transfer and prove long-term viability in the bladder. The cells need to be fully differentiated so there is no regression after implantation in the bladder. Using the patient’s own stem cells for differentiation lowers the risk of immunologic graft rejection and because of the self-renewal nature of stem cells, provides a resource for continued cell therapy if needed. The ability to reliably direct and differentiate pluripotent stem cells in the bladder shows promise toward the future, but also holds promise and insight into other types of tissue that can be used in regeneration from stem cells.
Mark Rodgers
University of Pittsburgh School of Medicine
See Also: Bladder: Current Research on Isolation or Production of Therapeutic Cells; Bladder: Existing or Potential Regenerative Medicine Strategies; Bladder: Stem and Progenitor Cells in Adults.
Further Readings
Bajada, Stefan, Irena Mazakova, James B. Richardson, et al. “Updates on Stem Cells and Their Applications in Regenerative Medicine.” Journal of Tissue Engineering and Regenerative Medicine, v.2 (2008).
Bajek, Anna, Tomasz Drewa, Romana Joachimiak, et al. “Stem Cells for Urinary Tract Regeneration.” Central European Journal of Urology, v.65 (2012).
California’s Stem Cell Agency. “Turning Stem Cells Into Therapies.” http://www.cirm.ca.gov/our-progress/stem-cells-therapies (Accessed May 2014).
Osborn, Stephanie L., Rayikumar Thangappan, Ayala Luria, et al. “Induction of Human Embryonic and Induced Pluripotent Stem Cells Into Urothelium.” Stem Cells Translational Medicine, v.1 (March 20, 2014).
Sharma, Arun K., Matthew I. Bury, Natalie J. Fuller, et al. “Cotransplantation With Specific Populations of Spina Bifida Bone Marrow Stem/Progenitor Cells Enhances Urinary Bladder Regeneration.” Proceedings of the National Academy of Sciences of the United States of America, v.110/10 (2013).
Bladder: Existing or Potential Regenerative Medicine Strategies
Bladder: Existing or Potential Regenerative Medicine Strategies
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Bladder: Existing or Potential Regenerative Medicine Strategies
Regenerative medicine strategies are being researched and developed for every type of tissue and organ within the urinary system. The bulk of research involving regenerative medicine strategies with the bladder has taken place within the past decade. There exists a wealth of regenerative medicine technologies, with products in discovery, preclinical testing, and clinical trials. Research is underway to expand both cell source and biomaterials options for regenerative medicine applications. Researchers have established the feasibility of using regenerative medicine to treat neurogenic bladder and the future promises that regenerative medicine therapies and treatment options will expand to patients with other bladder diseases and, ultimately, additional organs.
In modern bladder regeneration research, precursor urothelial and smooth-muscle cells are isolated and expanded to numbers suitable for regenerative medicine strategies from normal and neurogenic human bladder tissue. To use regenerative medicine strategies on the bladder, urothelial and smooth-muscle cells have been isolated and expanded to numbers suitable for regenerative medicine approaches from normal human bladder tissue. This has established a greater ability for clinicians to use autologous homologous cells in regenerative medicine for bladder augmentation and regeneration in humans. In preclinical studies, cell-free and progenitor cell-seeded, bladder-molded scaffolds made from specially constructed biodegradable polymers were compared. Several studies reveal that cell-free implants resulted in bladder wall reparative healing and the cells were needed to regenerate the bladder. In addition, the cell-seeded implants had a long-term durability and were bioresponsive to the recipients’ needs for bladder functionality.
Regenerative medicine therapies for bladder augmentation following cystoplasty were first used in humans in 1998. In a small study, implants made from collagen or poly(lactic-co-glycolic acid) (PLGA)-based scaffolds seeded with autologous progenitor cells were tested. Patients showed increased compliance, decreased end-filling pressures, increased capacities, and longer dry periods after implantation. This initial study first established the feasibility and safety of using regenerative medical products as an alternative to gastrointestinal tissue for bladder generation. Since this study, the production of progenitor cell-seeded, PLGA-based scaffolds for clinical use has been standardized and is currently in phase II clinical trials. Future goals are products for urinary diversion and total-bladder replacement, ultimately enhancing or fully restoring bladder function and nerve development.
Regenerative Medicine Strategies for Treatment of Neurogenic Bladder
Neurogenic bladder is a broad term describing various neurologic dysfunctions in the bladder and external urethral sphincter caused by disease or damage. The present standard for surgical treatment of the bladder is bladder augmentation using intestinal segments. However, intestinal tissues possess various functional characteristics similar to bladder tissue. There are a wealth of complications that can arise from this therapy. Regenerative medicine uses combinations of cells and biomaterials to induce regeneration of healthy tissue