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Bladder: Development and Regeneration Potential

Since the discovery of stem cells and the understanding of their propensity for self-renewal and differentiation into a variety of cell progenitors, there has been promise for use in cell therapy. The pluripotent nature of stem cells has made them a target for research and development in pathologies affecting all parts of the human body, including the urinary bladder. Urologists have traditionally treated bladder replacement with complicated bowel resection or with less invasive methods such as autologous urothelial or smooth muscle cells. However, this method is not effective in patients where the cells are compromised, like cancer. However, new research has shown that using bone marrow mesenchymal stem cells (MSCs) or human induced pluripotent stem cells (iPSCs) from the skin could have a great impact on tissue regeneration in the bladder because of the differentiation potential of these cells.

The Differentiation Potential of Stem Cells

The research and therapeutic potential of stem cells comes from the cell’s ability to self-renew and also produce progeny cells that can differentiate into many different cell types. These cells are committed progenitors that can go down any one of multiple pathways to create tissue- and organ-specific cell types. Stem cells undergo asymmetric division, producing one cell with a fate to become a differentiated progenitor and one cell that remains as a pluripotent stem cell. This special division and unique ability can be controlled by the microenvironment that surrounds the stem cells. The extracellular components surrounding the cells, secreted signaling proteins, and various cell types surrounding the stem cells play a large role in self-renewal and how the progenitors differentiate into specific cell types. The key to understanding this asymmetrical division and the pathways to differentiation lie in figuring out the minimal signals and extracellular proteins that must be present in the microenvironment to make the stem cells thrive. For stem cells to reach their full therapeutic potential, reaching an understanding of the biology of these cells sufficient to be able to recreate that microenvironment in-vitro is paramount, and the same is true in developing bladder tissue from stem cells.

Bladder Tissue’s Prospective for Regenerative Therapy

Urologists, researchers, and tissue engineers have long been striving for the best methods for bladder reconstruction or regeneration. Stem cell technologies have been considered in pathologies that lead to malfunction or malformation of the bladder, such as spina bifida, interstitial cystitis, stress urinary incontinence, and cancer. For decades, surgeons constructed urinary bladder tissue using the ileum. Later, bowel walls were utilized to recreate urethra and tissue grafts for the bladder. However, this comes with potential complications like adhesions, mucus secretions, metabolic derangements, and even malignant cyst formation. This is also a very invasive procedure. Researchers also harvested autologous urothelial and smooth muscle cells, seeded them onto a biodegradable scaffold, and repopulated those grafts in healthy bladder tissue. This method, however, only works for patients with healthy, uncompromised cells that can be harvested. In cancer patients, the use of autologous bladder cells is too risky to use for tissue grafts. In addition, the size of the bladder surface limits how large a graft can be.

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