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 and offers an alternative approach for the replacement of lost or deficient organs including the bladder. There exists promising research using the foundations of regenerative medicine that have been demonstrated in children with neurogenic bladder caused by myelomeningocele, which is a birth defect in which the spinal canal and backbone do not close.
There are several preclinical experiences with alternatives to enterocystoplasty. Tissue expansion involving the progressive dilation of the bladder with an expansion balloon device has been suggested as a method of bladder augmentation. However, this has not yet been attempted clinically. In preclinical models, tissue expansion increased bladder capacity significantly. Histology of bladder tissue revealed that the bladder compliance was in the normal range. Seromuscular grafts replacing the traditional gastrointestinal segments used for bladder augmentation was another attempted approach. In preclinical models, seromuscular flaps used for bladder augmentation revealed normal re-epithelialization, but the tissue experienced significant shrinkage that severely limited the clinical feasibility of the technique. Using de-epithelialized segments over native tissue was also attempted and revealed little success. In recent years, seromuscular grafts have mostly been abandoned. Extracellular matrices and synthetic grafts for bladder repair have been used to encourage growth of bladder wall segments for partial bladder repair in vivo. These matrices are prepared by mechanical and chemical treatment of native tissue from allogenic or xenogenic donors to remove all the cellular components. In preclinical models of bladder augmentation, small intestine submucosa resulted in bladder wall regeneration in vivo. Bladder repair was shown to be more stabilized when small intestine submucosa was gained from distal ileum.
Regenerative Medicine Strategies Involving Biomaterials
Biomaterials used in regenerative medicine are constructed to support restoration of biological properties of original tissue. Biomaterials may act as a carrier for transplanted cells and provide support for structured tissue formation by endogenous cells. Biomaterials may be synthetic materials, or they may be derived from natural substances. In some instances, both techniques are used. Tissue matrices from naturally derived materials are considered to have biological properties that can mimic native tissue or organ extracellular matrices. Synthetic polymers, naturally derived materials, and acellular tissue matrices are the three primary classes of biomaterials that may be used in regenerative medicine therapies for the bladder and other organs. On the other hand, synthetic scaffolds can be produced on a large scale with controlled properties of strength, microstructure, and degradation rate.
One advantage to using biomaterials is that they can physically control where and when injected cell suspensions localize in the body. Biomaterials can also provide guidance for appropriate development of new tissues. Furthermore, biomaterials are specially designed as artificial extracellular matrices that can deliver growth factor signals to regulate and improve cellular function.
Regenerative Medicine Strategies Involving Cells
Researchers can isolate cells from several sources. Some cells, autologous cells, are isolated from the recipient of the regenerative medicine procedure. In contrast, cells derived from any other human being besides the recipient are allogeneic. Cells obtained from nonhuman origins are called xenogeneic cells. Cells can be applied in different physical states. Cells can be administered in a suspension or attached to a support matrix. The goal of the chosen approach is to repair the tissue and organs with the most native outcome and the fewest complications. One benefit to using autologous homologous cells is rejection is generally not an issue and so avoids the use of immunosuppressant therapies. The cells are also re-implanted into a homologous tissue. When planning regenerative medicine
