Hart, M., K. Neumayer, M. Vaegler, L. Daum, B. Amend, K. Sievert, and W. Aicher. “Cell-Based Therapy for the Deficient Urinary Sphincter.” Current Urology Reports, v.14 (2013).
Kim, J., S. Lee, Y. Song, and H. Lee. “Stem Cell Therapy in Bladder Dysfunction: Where Are We? And Where Do We Have to Go?” BioMed Research International (2013).
Kim, J., H. Lee, and Y. Song. “Treatment of Bladder Dysfunction Using Stem Cell or Tissue Engineering Technique.” Korean Journal of Urology, v.55 (2014).
Bladder: Stem and Progenitor Cells in Adults
Bladder: Stem and Progenitor Cells in Adults
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Bladder: Stem and Progenitor Cells in Adults
The urinary bladder is a muscular sac in the pelvis, just above and behind the pubic bone. The bladder consists of a transitional epithelium and three layers of smooth muscle tissue. When the bladder is empty, it is about the size and shape of a medium-sized pear. The bladder’s primary purpose is to store urine, which is made in the kidneys and travels through the ureters to the bladder. The bladder essentially enables voluntary and infrequent urination. There exist a number of clinical applications in using stem cells to treat various bladder conditions. Researchers already use artificially grown skin tissue in surgery, and scientists are working on a variety of strategies to treat bladder dysfunction using stem cells. The goal is for clinicians to be able to create patches or full replacements for virtually every organ in the body, including the bladder.
Pluripotent Stem Cells for Bladder Regeneration
Scientists have been studying the process by which clinicians can generate bladder urothelium from human pluripotent stem cells. Human stem cells are promising sources for bladder regeneration. Pluripotent stem cells are promising because they can differentiate into any cell type and proliferate indefinitely in vitro. Researchers have developed a protocol to differentiate human pluripotent cells into bladder urothelial cells. The protocol will be beneficial for producing cells for bladder regeneration and studying normal and pathological development of the human bladder urothelium in vitro.
Epithelial integrity in organs is maintained via a regulated proliferation and differentiation of organ-specific stem and progenitor cells. The epithelia of certain organs, such as the intestine, regenerate constantly and remain continuously proliferative. However, not all organs act in this manner. The bladder shifts from near-quiescence to a highly proliferative state in response to epithelial injury.
Current research focuses in identifying the molecular and cellular mechanisms involved in this injury-induced mode of regenerative response displayed by organs. In one study, investigators revealed that the bladder’s proliferative response to infection or chemical injury is regulated via signal feedback between basal cells of the urothelium and the stromal cells that underlie them. Basal cells include stem cells capable of regenerating all cell types within the urothelium, and are marked by expression of a specific secreted protein signal.
Stem Cells in the Bladder
Patients who suffer from spina bifida often experience degrees of bladder malfunction. The traditional solution, which uses a length of the intestine to reconstruct the bladder, is fraught with complications. Using intestine tissue to reconstruct the bladder may elevate the patient’s risk for bladder cancer. Bladders constructed from induced pluripotent stem cells (iPSCs) offer a new and innovative form of clinical treatment of the bladder using stem cells. Researchers have successfully been able to convert mouse embryonic stem cells and induced pluripotent stem cells into the bladder’s smooth muscle cells. The specialized epithelial cells that line the bladder have also undergone conversion. The findings revealed the cells were expressing the full range of proteins found exclusively in bladder epithelium. Investigators hope to repeat this success using human iPSCs.
Scientists at the University of California–Davis set out with a goal to utilize human stem cells to regenerate bladder tissue that could be used by clinicians to replace a malfunctioning bladder with functional tissue. The team was able to successfully develop bladder cells using two categories of human stem cells. The key experiment utilized induced pluripotent stem cells that were derived from lab cultures of human skin cells and umbilical blood cells that had been genetically reprogrammed to convert to an embryonic stem cell substitute. The research team is now looking to demonstrate safety and effectiveness of the grafts of bladder tissue grown from human stem cells. The source of the graft would be induced pluripotent stem cells derived from a patient’s own skin or umbilical cord blood cells. It would be highly beneficial for clinicians to use this type of tissue because it would significantly diminish the risk of immunological rejection that plagues most transplants. During their research, Kurzrock and his colleagues developed a protocol to develop the pluripotent cells into bladder cells. Importantly, the cells proliferated over a long period of time, a feature essential for tissue regenerative medicine strategies.
Patients suffering from spina bifida who are afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying levels of dysfunction. The current standard for treatment of the neurogenic bladder is through surgical intervention in the form of enterocystoplasty. However, it is still considered a stop-gap measure and comes with a number of complications due to the use of the bowel as a source of replacement tissue. At the moment, modern bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when applying autologous cell groups. In one paper, researchers demonstrated the role of two specific groups of bone marrow stem and progenitor cells used in conjunction with a synthetic elastomeric scaffold that provides a unique and alternative means to current bladder regenerative approaches. The researchers provided data to suggest that autologous bone marrow stem and progenitor cells may be used as an alternate, nonpathogenic cell source for spina bifida patient-specific bladder tissue regeneration in place of current treatment procedures. These research findings have implications for other bladder regenerative therapies.
Krishna S. Vyas
University of Kentucky College of Medicine
Shalin Jyotishi
University of Georgia
See Also: Bladder: Cell Types Composing the Tissue; Bladder: Development and Regeneration Potential; University of California, Davis.
Further Readings
De Coppi, Paolo, et al. “Amniotic Fluid and Bone Marrow Derived Mesenchymal Stem Cells Can be Converted to Smooth Muscle Cells in the Cryo-Injured Rat Bladder and Prevent Compensatory Hypertrophy of Surviving Smooth Muscle Cells.” The Journal of Urology, v.177/1 (2007).
Kurzrock, Eric, Deborah Lieu, Lea deGraffenried, et al. “Label-Retaining Cells of the Bladder: Candidate Urothelial Stem Cells.”Renal Physiology, v.294 (2008).
Nguyen, M. M., D. K. Lieu, L. A. deGraffenried, et al. “Urothelial Progenitor Cells: Regional Differences in the Rat Bladder.”Cell Proliferation, v.40/2 (2007).
Oottamasathien, Siam, et al. “Directed Differentiation of Embryonic Stem Cells Into Bladder Tissue.” Developmental Biology, v.304/2 (2007).
Shin, Kunyoo, John Lee, Nini
