Augmentation or replacement of the bladder is often necessary for the treatment of adults with bladder cancer and children with spinal cord injury or spina bifida. Current surgical techniques utilize segments of intestine or stomach as a substitute for bladder wall. Use of intestinal segments is associated with many complications including infection, stones, salt imbalance, and most concerning, cancer. An ideal substitute for bladder wall would be bioengineered bladder tissue. Stem cells appear to be the ideal solution for bioengineering tissue. The ability to induce human embryonic stem cells (hESC) or induced pluripotent stem cells (iPSC) into urothelium, the cells that line the bladder, would provide a major advancement in the tissue engineering field, scientifically and clinically.
Our specific aims are to induce the differentiation of hESC into urothelium via cell signaling. We will also investigate the genes involved in this process. And, we will test the feasibility of transplanting hESC-derived urothelium into a bladder.
In the last year we have made progress developing a technique for the induction of human embryonic stem cells into urothelium. In the developing embryo, embryonic stem cells are preprogrammed to turn into urothelium when induced by the appropriate and timely signals. The challenge is to simulate this in a culture dish. We have found that embryonic stem cells can be induced to form urothelium when they are exposed to growth factors released by cultured adult urothelium. We have done this by growing them together (without contact) and currently are testing solutions with these growth factors. We are also studying the molecular mechanisms and genes involved in this process.
We have also made significant progress on our third aim which is to test the feasibility of transplanting cultured urothelium. In a small animal model we have been able to reliably transplant these cells into the bladder and demonstrate their survival and incorporation into the bladder. We are currently testing better techniques of transplantation and following the animals longer to determine the life span of these cells.
This investigation will lead to advances in stem cell biology in an important area not addressed by other scientists. The successful completion of this project will improve human health, indirectly through increased knowledge of differentiation pathways relevant to normal development and neoplasia, and directly through development of novel methodologies for bioengineering tissue for adults and children with urologic disorders and cancer. We are working in a very novel field, which has a high potential to save lives and to vastly improve the quality of life for many patients who need their bladder removed or enlarged.