I am happy to inform you that this project has been fully funded and I began working on it recently. Human pluripotent stem cell-derived pancreatic beta cells are promising cell source for the treatment of diabetes. However, to use these beta cells in clinic, we have to overcome several major problems, the tumorigenesis risk caused the remaining stem cells, and the high cost of producing these beta cells using these time-consuming protocols. The aim of this project is to purify and expand the intermediate cell types generated in the process of inducing human pluripotent stem cell into pancreatic beta cells, and thus to (a) exclude remaining stem cells, and (b) greatly reduce the cost and time by shortening the differentiation protocol.
In the first stage of this project I will differentiate human pluripotent stem cells into beta cells using our step-wised protocol. We will then purify the intermediate cell types using stage-specific gene markers (e.g. fluorescent proteins, surface proteins). These isolated cells will be tested using different cocktails of factors (growth factors and pathway modulators).
If we could find certain condition(s) which could expand some intermediate cell type(s), we will then investigate these expanded cells for their ability to differentiate further into functional beta cells. We will also test if these expanded intermediate cells could generate human pancreas or pancreatic tissue after injecting into pancreas-deficient animal embryos.
The project will be completed on April 30th 2020. Thank you for your generosity and for allowing DRC to support innovative scientific inquiry until diabetes is eliminated.
Currently, the best treatment for T1D is the transplantation of pancreatic beta cells (in the form of pancreatic islet) from a donor. However, pancreas donations are extremely limited. Human stem cells multiply infinitely and differentiate into different cell types that can be used in cell replacement therapy, providing new hope for curing T1D. After more than 15 years of continual endeavor, scientists have successfully converted human stem cells into functional insulin-producing pancreatic beta cells. The stem cell-derived pancreatic beta cells have been demonstrated to cure T1D in experimental animals. In fact, stem cell-derived pancreatic beta cells are very close to being used in the clinic to treat patients.
However, before we can use stem cell-derived pancreatic beta cells in the clinic, we first have to overcome three problems:
- Safety issue: tumors are frequently observed after transplantation of certain types of human stem cells.
- High Cost: The current seven-step process is expensive.
- Time-consuming: The seven-step protocol takes more than one month to complete.
My strategy is to improve the generation of pancreatic beta cells in a safe and cost-effective way. I also intend to generate the entire human pancreas by injecting intermediate pancreatic cells into pancreas-deficient animal embryos (such as rabbit and sheep). Since the experimental animal embryo can’t develop a pancreas, the human pancreatic cells may fill the developmental gap and form a human pancreas in the animal.
Expectations from the project:
- Development of purified pancreatic progenitors or later stage cells, that only generate pancreatic cells, thereby preventing the potential for tumor formation.
- Reduce the process from 7 steps to 1-3 steps, enhancing the stability of the cells and greatly reducing time and cost.
- Making beta cells in bulk which is more efficient and suitable for clinical applications.