must consider the condition of the tissue or organ to be replaced. In some cases, diseased organs may not provide suitable cells for regenerative medicine techniques either because of expansion problems or innate qualities that are incompatible with the type of healing process required. For example, re-introducing malignant cells into a scaffold designed to replace tissue or organs removed for cancer treatment would not be a desirable strategy. In some disease states, genetically normal progenitor cells live in the tissue and are reservoirs for new cell formation. These normal progenitor cells are programmed to give rise to normal tissue even if they may reside in a diseased environment. In regenerative medicine, tissue and organ-resident progenitor cells remain a very promising area of ongoing investigation and research.
Regenerative Medicine Strategies Using Progenitor and Stem Cells
The two important characteristics for cells in regenerative medicine therapies are the potential for self-renewal and differentiation. Cells limited in their capacity for self-renewal divide in culture for a finite number of passages. In contrast, cells with unlimited self-renewal may be grown in culture for extended times. Cell differentiation potential can be unipotent, multipotent, or pluripotent. Unipotent cells keep their phenotype. In the bladder, urothelial and bladder smooth-muscle progenitor cells isolated from bladder biopsies are unipotent. Multipotent cells are able to be guided into several phenotypes depending on culture conditions, but the range of possible phenotypic outcomes is more restricted. Bone marrow adipose tissue is a common source of multipotent progenitor cells. These cells can be turned into chondrocytes, adipocytes, or smooth-muscle differentiation pathways. Pluripotent cells have unlimited differentiation potential. Pluripotent cells can become virtually any cell in the body. An example of pluripotent cells are embryonic stem cells. Autologous homologous cells are typically progenitor cells and are usually preferred for regenerative medicine techniques. Sometimes, heterologous cells are used in situations when autologous cells cannot yet be expanded from a particular tissue, such as the pancreas, or are otherwise unavailable for expansion (total-bladder replacements for bladder cancer patients).
Researchers have invested a great deal of time and energy looking into pluripotent stem cells, because of their unlimited self-renewal and plasticity. However, clinical applications remain limited. Pluripotent stem cells are generally allogeneic, and there is a possibility to create immune responses when using them. Furthermore, issues persist with using embryonic stem cells and controlling localization and phenotype for the specific time frames needed for regenerative medicine and tissue-engineering processes. Embryonic stem cells can also form teratomas, which further complicate their implication into clinical procedures. Developers of products using embryonic stem cells will need to address these issues when seeking regulatory approval. Last, many countries have limited or banned clinical use of embryonic cells, because of ethical concerns.
Multiple preclinical studies have demonstrated that bladder implants with progenitor cells elicited superior structure and function when compared with cell-free implants.
Regenerative Medicine Techniques Using Cells Derived From Cloning Techniques
Somatic cell nuclear transfer (SCNT) is being researched as another possible source of pluripotent stem cells for regenerative medicine treatment of the bladder. SCNT involves implanting a nucleus from a donor somatic cell into an unfertilized oocyte and generating embryonic stem cells from the merging of donor genetic material and oocyte cytoplasm. SCNT is different from reproductive cloning in that cells from a SCNT procedure are generally allowed to develop into a blastocyst that is implanted into a pseudopregnant female, giving rise to a baby that is genetically identical to the donor of the nucleus. In regenerative medicine, cells from a SCNT procedure are propagated in cell culture and not as implantable embryos.
In conclusion, there exist a wide variety of regenerative medicine strategies and techniques for the treatment of the human bladder. Current research focuses on the expansion of existing techniques. Further studies may analyze the effectiveness of generated bladders in the long term. Longitudinal studies may prove useful in providing clinicians with effective and safe treatments.
Krishna S. Vyas
University of Kentucky College of Medicine
Shalin Jyotishi
University of Georgia
See Also: Bladder: Stem and Progenitor Cells in Adults; Neural: Development and Regeneration Potential; Tissue Regeneration: Humans.
Further Readings
Atala, Anthony. “Recent Developments in Tissue Engineering and Regenerative Medicine.” Current Opinion in Pediatrics, v.18/2 (2006).
Bajada, Stefan, et al. “Updates on Stem Cells and Their Applications in Regenerative Medicine.” Journal of Tissue Engineering and Regenerative Medicine, v.2/4 (2008).
Fodor, W. L. “Tissue Engineering and Cell Based Therapies, From the Bench to the Clinic: The Potential to Replace, Repair and Regenerate.” Reproductive Biology and Endocrinology, v.1 (2003).
Gimble, Jeffrey, Adam Katz, and Bruce Bunnell. “Adipose-Derived Stem Cells for Regenerative Medicine.” Circulation Research, v.100 (2007).
Sharma, Arun, and Manoj Rao. “Urinary Bladder Regenerative Medicine.” Stem Cells and Cancer Stem Cells, v.9 (2013).
Soler, Roberto, Claudius Fullhase, and Anthony Atala. “Regenerative Medicine Strategies for Treatment of Neurogenic Bladder.” Therapy, v.6/2 (2009).
Bladder: Major Pathologies
Bladder: Major Pathologies
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Bladder: Major Pathologies
Bladder pathologies often involve injury and dysfunction of the smooth muscle of the bladder as well as its nerve supply. Stem cell therapy for bladder pathology is directed toward regeneration of functional muscle and nerves to restore bladder function. There are also treatments using stem cells that take advantage of other specific properties that stem cells possess. Currently, many alternative treatments exist for these bladder pathologies, but, the goal of stem cell therapy research is to reduce the adverse effects of treatment and to reduce cost. Many of the pathologies described below have suboptimal treatments. Without treating the conditions described, one risks complications, such as urinary tract infections or loss of urinary continence.
Stem cells begin by migrating to the injured tissue, such as the bladder. This migration is directed by the release of cytokines from the damaged tissue. Next, the stem cells differentiate into the specific tissue needed, such as smooth muscle and neural tissue. Finally, there is the paracrine effect, in which stem cells release certain factors that induce tissue regeneration and modulate inflammatory responses to injury in the original tissue. Through these mechanisms, stem cells can lead to regeneration and growth of injured tissue and restoration of function of damaged organs.
Stress Urinary Incontinence
Stress incontinence is a common medical condition that affects over 200 million people in the world. It is defined as involuntary leakage of urine with exertive actions such as coughing or sneezing that increase intra-abdominal pressure. This happens when the muscular internal or external sphincter of the bladder outlet
