The bladder serves as a reservoir for the storage and emptying of urine. Spina bifida and bladder cancer are conditions that adversely affect the bladder, and many patients must undergo bladder replacement. Unfortunately, current bladder replacement techniques require the use of intestine, which is associated with significant perioperative morbidity and long-term complications. Recently, tissue engineered bladder segments derived from autologous biopsy have been identified as an alternative to the use of intestine for bladder replacement in both animal studies and in clinical trials.
Unfortunately, suitable unaffected donor cells may not exist in patients with spina bifida or bladder cancer. In these situations, hESCs are envisioned as a viable source of cells from which the desired tissue can be derived. Combining the techniques learned in tissue engineering over the past few decades with this potentially endless source of versatile cells could lead to novel sources of replacement organs such as the bladder.
This proposal will build upon principles from both tissue engineering and developmental biology with the intent of bioengineering bladder tissue derived from hESCs to avoid the complications and morbidity associated with the use of intestine for bladder replacement.
In addition to NIH-approved hESC lines, this proposal will involve the use of non-NIH approved hESC lines that were developed in xenogen-free and pathogen-free conditions, which would make them eligible for future clinical applications. This is in contrast to the approved hESC lines on the NIH registry, which were contaminated with mouse products.
In summary, this proposal will investigate the targeting of lineage-specific differentiation of hESCs toward the bladder cell lineages for bladder tissue engineering applications. Due to ongoing clinical studies using constructs derived from autologous bladder cells, the transition to clinical applications should be greatly shortened. The findings will greatly improve the lives of patients with spina bifida and bladder cancer, and will help to solidify California’s leadership in these fields.
Statement of Benefit to California:
This proposal will utilize novel hESC lines that were developed outside of the United States in political and social environments that have allowed rapid advancements in human embryonic stem cell research over the past 10 years. These cell lines include those that were derived in xenogen-free and pathogen-free conditions that render them eligible for future clinical applications. As these cell lines have not been used in the United States thus far, this proposal will allow the importation of these novel stem cell lines, which eventually can be made available to all interested scientists in California and the rest of the United States.
In addition, this proposal will investigate the targeting of lineage-specific differentiation of hESCs toward the bladder cell lineages for bladder tissue engineering applications. Due to ongoing FDA-approved clinical studies using tissue engineered constructs derived from autologous bladder cells, the transition to clinical applications should be greatly shortened. The findings will greatly improve the lives of patients with spina bifida and bladder cancer by avoiding the use of intestine, and will help to solidify California’s leadership in these fields.