Grant: Operating Grant - PA: Genetics (Bridge Funding: Research Priorities)

Human pluripotent stem cells (hPSCs) have the special ability to "expand" - make copies of themselves - and give rise to all cell types of the body. Since their discovery over 20 years ago, hPSCs have opened the door to producing cell therapies by transplanting lab-grown cells into the body to restore damaged function. With several clinical trials already underway, such as the transplantation of beta cells derived from hPSCs to treat diabetes, clinical demand for hPSCs is growing. Canada's booming biotechnology sector is strategically positioned to meet this demand, with the capability of growing billions of hPSCs for cell therapy production. However, these hPSC expansion pipelines are currently plagued by abnormal cells, which emerge as hPSCs divide and acquire undesirable genetic changes. These cancer-like cells outgrow normal hPSCs and go on to overtake the cell batch, rendering it unsafe for clinical use. To tackle this significant challenge, we will use a bioengineering approach to detect, remove, and curb the growth of abnormal cells in culture. We will use our existing cutting-edge genetic tools to track each hPSC, providing a high-resolution look at the growth of each cell. Using computational models, we will untangle these complex datasets to identify all problematic cells based on their cancer-like growth properties, regardless of the genetic changes they carry. To preserve the safety of costly hPSC batches, we will both optimize culture parameters to limit the growth of abnormal cells and use new genetic tools to remove these cells from batches. With support from translational partners, we will create the first standardized quality control strategy for hPSCs, ensuring that all cell batches meet rigorous standards for clinical use. Our technology will enable the safe and reliable large-scale production of hPSCs, bolstering Canada's position as a world leader in cell therapy manufacturing for regenerative medicine.