Stem Cell Treatments for Bladder Dysfunction


Spina bifida is a birth defect in which the backbone and spinal canal do not close before birth. The damage to the central nervous system affects various organs that receive nervous inputs from the spinal cord and one such organ is the urinary bladder. A condition called “neurogenic bladder” results from an inability of the nervous system to properly control the urinary bladder and the muscle tissue that lines the wall of the bladder. Neurogenic bladder can lead to spasms and a pressure build-up in the bladder. This results in urinary incontinence, and children with spina bifida and neurogenic bladder often have an urge to urinate after drinking comparatively small amounts of liquid. They can also involuntarily leak urine, and this creates a great deal of social embarrassment and emotional stress. If untreated, the long-standing and frequent pressure build-up in the bladder can lead to infections and even kidney damage.

Spina bifida

Surgical treatments for neurogenic bladder involve reconstruction of the bladder that increases its size by grafting patches from the patient’s bowel. Because the graft comes from the patient’s own body, it is unlikely that the immune system will reject these grafts. Also, the intestinal tissue patches are, on the average, strong enough to withstand the pressures in the bladder. However, there is a certain incompatibility between intestinal and bladder tissue, and this can cause long-term complications that include urinary tract infections, urinary tract stones and, rarely, cancers. Thus, researchers have been searching for newer safer patches which resemble the actual bladder wall.

Northwestern University researchers have published a study that used stem cells of children with spina bifida to generate tissue patches for bladder surgery. This paper, “Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration,” was published in the Proceedings of the National Academy of Sciences. Arun Sharma and colleagues from Earl Cheng’s laboratory isolated two types of cells from the bone marrow of child spina bifida patients. They isolated mesenchymal stem cells (MSCs) and CD34+ cells, which are stem and progenitor cells that usually give rise to blood cells. Sharma and her colleagues used these cells to coated molds that were made with a special polymer scaffold called POC (poly(octanediol-co-citrate). These cell-filled molds were used to create a patch graft that was transplanted into rat bladders. This type of surgery is not that unlike the bladder augmentation surgery used for spina bifida patients.

Next, the Cheng lab workers determined if the human tissue survived in the implanted patch. In those cases where both human cell types (MSCs and CD34+) were combined, over half the implanted patch was covered with muscle tissue, four weeks after the implantation. However, if only CD34+ cells were used, only a quarter of the patch was covered with muscle tissue. Interestingly, the implanted patch also showed evidence of some peripheral nerve growth and blood vessel formation, both of which are found in healthy, normal bladder walls. These experiments demonstrate suggest that a patient’s own bone marrow stem cells can be used to help construct a tissue patch that can potentially act as a graft patch for bladder augmentation surgeries. Also, since some nerve growth in the implanted patch was observed, and this definitely an exciting result. Could it be possible to re-connect the reconstructed bladder tissue with the main nervous system? Possibly, but the most severe cases of neurogenic bladder are almost certainly more difficult cases to treat successfully.

bladder_wall_pic

Despite the exciting possibilities in this study, there are some caveats. First of all, was the muscle formed from the stem cells or the surrounding tissue? It is not clear from this paper, and since implantation of an empty POC scaffold without any human stem cells results in 20% coverage with muscle tissue, at least some of the newly formed muscle tissue is actually derived from the host rat and not from human stem cells. Secondly, how do these patch grafts compare to the intestinal patches? This was not assessed. Finally, rats with neurogenic bladder were not implanted, and this is an important control, since it is at least possible, that the muscle growth would be less robust in an animal with neurogenic bladder. Thus, despite this great potential shown in this paper, several questions remain.

A second paper used a very different approach. Debra Franck and others in Joshua R. Mauney’s lab at Harvard Medical School coated a silk thread scaffold with extracellular matrix proteins and coated with smooth muscle cells that were made from induced pluripotent stem cells into the smooth muscle cells. Unfortunately, Franck and colleagues did not evaluate the newly created patch in a living animal. Also, this paper used mouse induce pluripotent stem cells, and it is not clear that human induced pluripotent stem cells would be able to do the same thing.

While these two studies are strictly experimental, they might provide some new avenues of research for new treatments for neurogenic bladder.