Grant Award Details
Deriving pluripotent stem cell-derived bladder epithelial progenitors for definitive cell replacement therapy of bladder cancer
Grant Application Details
- Pluripotent stem cell-derived bladder epithelial progenitors for definitive cell replacement therapy of bladder cancer
We will 1) identify non-invasive bladder cancer patients with (pre)cancerous urothelium by single-cell RNA-seq and 2) replace this dangerous lesion with normal hESC-derived bladder progenitors.
Replacement of corrupted (pre)cancerous urothelium with pluripotent cell-derived normal bladder progenitors will provide a definitive treatment for bladder cancer, expected to eliminate recurrence.
Major Proposed Activities
- To develop a diagnostic surface marker assay to quantify the purity of hPSC-derived human bladder progenitor populations
- To use single-cell RNA-seq to determine the purity of hPSC-derived human bladder progenitors and how closely they resemble primary human bladder cells
- To test engraftment of primary mouse bladder stem cells, and eventually, hPSC-derived bladder progenitors, in injured mouse bladders
- To profile (pre)cancerous bladder cells from patient samples and to develop diagnostic tools to monitor their spread using single-cell RNA-seq
Bladder cancer frequently recurs and progresses after treatment because of an extensive reservoir of (pre)cancerous cells that can serve as a source for development of new cancers. We propose to develop a stem cell-based cell replacement therapy to eliminate the devastating effects of bladder cancer recurrence and progression, and reduce the need for and expense of continuous patient monitoring. We also propose to develop methods to identify patients that would benefit most from such treatment.