and prevents leakage of fluid from the bladder. When the bladder is filled, the sphincter relaxes and the bladder contracts, thus emptying the urine.
Various Bladder Tissue Types
A smooth glistening tissue lines the inner surface of the bladder. This tissue is known as the mucosa and it is made up of transitional epithelial cells in a layer known as the urothelium.
A layer of connective tissue, nerves, and blood vessels form the layer next to the urothelium.
Next to this layer is the muscular bladder wall, which is formed by a layer of smooth muscle cells. The primary function of the muscular layer is to contract the bladder to excrete the stored urine. This layer is called the muscularis propria.
This layer of muscle cells is surrounded by the outermost layer of fat.
The transitional epithelial cells that line the interior of the bladder can transform into cancerous cells, thus leading to bladder cancer.
Bladder Dysfunctions and Cancers
About 90% of bladder cancers are derived from the transitional epithelial cells. The cancer type is determined based on the appearance of the cells.
Types of Bladder Cancers
1 Transitional cell carcinoma: This is the most common type of bladder cancer, and the cells of this type of cancer resemble those of urothelial cells. About 90% of bladder cancers in the United States are of this type. Transitional cell carcinoma can be either invasive or noninvasive.
2 Squamous cell carcinoma: The cells of this cancer appear like the flat cells on the surface of the skin. Only 1% to 2% of the bladder cancers in the United States are of this type. These are mostly invasive.
3 Small cell carcinoma: These types of cancer account only for 1% of the bladder cancers in the United States. The cells of this type of cancer appear like nerve cells.
4 Sarcoma: These are cancers that originate from the cells in the muscular layer of the bladder.
Other Bladder Dysfunctions
Spina bifida is the most common congenital bladder dysfunction in the United States. This leads to permanent, disabling birth defects. Children with this disability are unable to ambulate without the assistance of wheel chairs and crutches. The bladder and bowel functions are also out of control in these children.
These bladder cancers and dysfunctions can be treated using the inherent potential of adult stem cells or progenitor cells. To understand how these stem cells help in treating bladder cancers and dysfunctions, a brief understanding of stem cells is essential.
Stem Cells and Their Inherent Potential
Some stem cells are totipotent and form the biological source material for all cells, tissues, and organs. Stem cells are unspecialized cells that can self-renew and can differentiate into other cell types. Self-renewal is the ability to divide and produce more stem cells. Differentiation is the ability to develop into other types of cells.
There are cells in certain tissues of humans called adult stem cells. Adult stem cells have the capacity to self-renew (divide and produce more stem cells) or differentiate (divide and give rise to more mature cells that are not stem cells). Cells that have the capability to differentiate but not to self-renew are called progenitor cells. Progenitor cells are the progeny of stem cells.
Adult Stem/Progenitor Cells in the Bladder
Potential stem cells that can differentiate into bladder cells have been identified by researchers at the University of California–Davis Children’s Hospital. These human bladder stem/progenitor cells possess the ability of self-renewal. CD34+ CD45– cells are the progenitor cell types in the bladder. The discovery of these adult stem cells in the lining of the bladder paves the way for future research that will lead to artificial regeneration of entire bladder tissue.
Bladder Tissue Regeneration and Treatment of Bladder Dysfunctions and Cancers
Stem cell therapies for bladder cancers and for disabilities like spina bifida are in experimental stages. Here are few experiments that were conducted to demonstrate the ability of stem cells to regenerate into bladder tissue.
Ability to restore the underactive bladder.
In an experiment for treating underactive bladder in the rat, which was due to bladder outlet obstruction, Nishijima et al. demonstrated that an intra-bladder injection of unsorted bone marrow cells in rats with underactive bladder helped to restore bladder contractile function.
Treatment of overactive bladder (OAB).
Huang et al., in an experiment to correct overactive bladder, demonstrated that an intravenous injection of adipose-derived stem cells (ASCs) showed improvement in tissue parameters and the urodynamics in rat models.
Mesenchymal stem cells (MSCs) for partial bladder regeneration study.
Sharma et al. investigated research for partial regeneration of the bladder using MSCs in baboon bladder models in which an area of the bladder was surgically ablated. It was found that the MSCs that had populated and engrafted the ablated areas demonstrated the ability for continual expansion and contractile cycles of a functional bladder.
Stem Cell Therapy Research and Challenges
Numerous investigations are being conducted for the regeneration of the entire bladder using bone marrow stem cells and MSCs. Identification and characterization of new sources of stem cells is an essential requirement for the growth of stem cell therapy. Though there are various opportunities for stem cell therapy, an array of challenges is to be faced. A better understanding of bladder cell biology might help devise efficient bladder regeneration therapies. While efficient regeneration or transplantation therapies have been developed, rigorous clinical trials must be performed to measure efficacy and safety. A particular concern is the risk of cancer that is inherent to all stem cell therapies because of the self-renewal capability of these cells. Overcoming these challenges will pave way for a future of bladder therapies.
Suganya Raphael
University of Madras
See Also: Bladder: Development and Regeneration Potential; Bladder: Major Pathologies; Bladder: Stem and Progenitor Cells in Adults; Cancer Stem Cells: Overview; Mesenchymal Stem Cells.
Further Readings
Fierabracci, A., P. Caione, M. Di Giovine, et al. “Identification and Characterization of Adult Stem/Progenitor Cells in the Human Bladder (Bladder Spheroids): Perspectives of Application in Pediatric Surgery.” Pediatric Surgery International, v.23/9 (2007).
Forbes, S. J., P. Vig, R. Poulsom, et al. “Adult Stem Cell Plasticity: New Pathways of Tissue Regeneration Become Visible.” Clinical Science, v.103 (2002).
Nishijima, S., K. Sugaya, M. Miyazato, et al. “Restoration of Bladder Contraction by Bone Marrow Transplantation in Rats With Underactive Bladder.” Biomedical Research, v.28 (2007).
Sharma, Arun K., Matthew I. Bury, Andrew J. Marks, et al. “A Non-Human Primate Model for Urinary Bladder Regeneration Utilizing Autologous Sources of Bone Marrow Derived Mesenchymal Stem Cells.” Stem Cells, v.29/2 (2010).
Woo, L. L., S. T. Tanaka, G. Anumanthan, et al. “Mesenchymal Stem Cell Recruitment and Improved Bladder Function Following Bladder Outlet Obstruction: Preliminary Data.” Journal of Urology, v.185/3 (2011).