Grant Award Details
Curing bladder cancer by replacing corrupted urothelium with differentiated hES cells
<p>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 <em>in situ </em>(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.</p><p>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.</p><p>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.</p>
Grant Application Details
- Curing bladder cancer by replacing corrupted urothelium with differentiated hES cells
The goal of the proposed research is to use human embryonic stem cells to generate bladder epithelial progenitor cells that can be used to replace a cancerous bladder epithelium in vivo.
The long-term goal of the proposed research is to cure bladder cancer. Successful completion of this work may indicate that transplantation of differentiated pluripotent stem cells is a feasible cure.
Major Proposed Activities
- We seek to differentiate human embryonic stem cells into bladder epithelial progenitors. To this end, we will test stem cell culture conditions that promote the bladder epithelial progenitor state.
- Using a mouse model for bladder cancer, we will determine whether transplantation of differentiated human embryonic stem cells can functionally replace a cancerous bladder epithelium.
Statement of Benefit to California:
The long-term goal of the proposed research is to develop a cure for bladder cancer, one of the most prevalent cancers worldwide. Muscle invasive bladder cancer (MIBC) is uniformly lethal if left untreated. Surgical removal of MIBC is frequently followed by recurrence and/or a dramatic reduction in quality of life. Moreover, bladder cancer is the most expensive cancer to treat per patient. A definitive cure for bladder cancer therefore would have wide-ranging positive impacts.
Source URL: https://www.cirm.ca.gov/our-progress/awards/curing-bladder-cancer-replacing-corrupted-urothelium-differentiated-hes-cells