Bladder Cells Derived From Umbilical Cord Blood and Skin Cells Stem Cells
The human bladder is lined with a specialized cell group called the urothelium. Urothelium is found throughout the urinary tract and it is very elastic. Guiding stem cells to develop into a proper urothelium has proved troublesome. Scientists have succeeded in devising a method for converting differentiating human pluripotent stem cells into urothelial cells. Two types of induced pluripotent stem cells were used. Genetically modified human skin cells and genetically modified umbilical cord blood cells were used to create bladder cells. These stem cells were successfully differentiated into bladder cells. Not only did the newly produced cells look like urothelium, but they also expressed a specific protein that is unique to the bladder and helps make it impermeable to toxins found in urine.
Krishna S. Vyas
University of Kentucky College of Medicine
Shalin Jyotishi
University of Georgia
See Also: Bladder: Development and Regeneration Potential; Bladder: Stem and Progenitor Cells in Adults; Cord Blood Stem Cells; Mesenchymal Stem Cells.
Further Readings
Bharadwaj, Shantaram, et al. “Multi-Potential Differentiation of Human Urine-Derived Stem Cells: Potential for Therapeutic Applications in Urology.” Stem Cells, v.31/9 (2013).
Drzewiecki, Beth, John Thomas, and Stacy Tanaka. “Bone Marrow-Derived Mesenchymal Stem Cells: Current and Future Applications in the Urinary Bladder.” Stem Cell International, v.2010 (2010).
Osborn, Stephanie, et al. “Induction of Human Embryonic and Induced Pluripotent Stem Cells Into Urothelium.” Stem Cells Translational Medicine (March 2014).
Shin, Kunyoo, et al. “Hedgehog/Wnt Feedback Supports Regenerative Proliferation of Epithelial Stem Cells in Bladder.” Nature, v.472 (2011).
Weinberg, Robert and Chiaho Shih. “Isolation of a Transforming Sequence From a Human Bladder Carcinoma Cell Line.” Journal of Tissue Engineering and Regenerative Medicine, v.2/4 (2008).
Bladder: Development and Regeneration Potential
Bladder: Development and Regeneration Potential
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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.
The Development of Stem Cells Into Bladder Tissue
The use of autologous MSCs may be an alternative to current methods in bladder tissue regeneration. Bone marrow MSCs have the potential to differentiate into cell types like chondrocytes, osteoblasts, cardiomyocytes, and skeletal muscle cells. Human embryonic stem cells (hESCs) have great differentiation potential as well, but they are harder to obtain and are not as plentiful to use in research and therapy. Induced pluripotent stem cells (iPSCs) have potential in stem cell research, including induction into urothelium, and is readily accessible without invasive procedures.
The idea remains to harvest iPSCs from hair follicles or MSCs from bone marrow to induce the naïve cells into adult bladder cells for use in regenerative medicine. Many questions are unanswered: Will the differentiated stem cells be viable after transplantation? Can the cells avoid sudden cell death that usually occurs a few hours after implantation? Are the cells capable and sufficient to promote nerve growth and angiogenesis?
A group at Northwestern University looked at a unique alternative to current bladder regeneration methods based around neurological problems arising from the diseases. In spina bifida, for instance, the nerves do not properly convey the messages between the brain and the bladder, and the patient is therefore unable to pass urine normally. Cell therapy presents an opportunity to correct this pathology. The research group combined an elastomer scaffold with similar mechanical properties to the bladder and seeded this scaffold with donor-matched MSCs plus spina bifida hematopoietic progenitor cells. This would use a combination of donor cells but also the patient’s own spina bifida donated cells to decrease rejection. Together, the two types of progenitor cells showed increased tissue vascularization and induction of peripheral nerve growth. These specialized grafts demonstrated urothelium regeneration. This cell regenerative therapy is an attractive alternative to surgical bowel augmentation procedures.
Kurzrock’s group at the University of California–Davis developed a lab protocol to proliferate specialized bladder cells in vitro utilizing autologous iPSCs taken from human skin cells, which lowers the risk for rejection. The method of reliably differentiating stem cells can lead to greater testing of new bladder tissue to check for true regeneration, continued viability, and the ability to repair itself just like real tissue would.