Curing bladder cancer by replacing corrupted urothelium with differentiated hES cells

In this project we sought to develop a novel cell replacement therapy to treat human bladder cancer. The development of the lethal form of bladder cancer (invasive carcinoma of the bladder epithelium), proceeds through a precursor stage, carcinoma in situ (CIS), that aggressively takes over the entire bladder epithelium before becoming invasive. Given the extensive spread of this corrupted bladder epithelium prior to invasion, wholesale bladder epithelial replacement at this intermediate stage may be essential for an effective bladder cancer cure. The strategy adopted is to generate bladder epithelial progenitor cells from human embryonic stem cells, and use these cells to replace the corrupted bladder epithelial cells of the CIS intermediate. The first step of this strategy, and the aim of this project, is to demonstrate proof-of-principle by replacing the bladder epithelium of mice with bladder epithelial progenitor cells from human embryonic stem cells.

In our work we successfully generated bladder epithelial progenitor cells from human embryonic stem cells, and we successfully bred mice in which we should be able to effectively remove the resident bladder epithelium. In future work, we will establish methods that allow us to replace the resident mouse bladder epithelium with the progenitor cells derived from human embryonic stem cells.

Successful completion of this work would indicate that a similar approach to cell replacement by differentiated hES cells could provide a definitive cure for bladder cancer patients, reducing the risk of recurrence and the need for expensive monitoring.