Grant Award Details
The objective is to develop stable, ex vivo culture conditions for mouse and human hematopoietic stem cells by modulating TPO signaling
Grant Application Details
- Optimizing self-renewal signaling kinetics to stabilize ex vivo hematopoietic stem cell expansion
Research Objective
We aim to develop conditions for stable expansion of blood stem cells outside of the body
Impact
Blood stem cells are a rare but necessary cell type for curative bone marrow transplantation and related gene therapies. Stable blood stem cell expansion will increase therapy availability and success
Major Proposed Activities
- Validate a fully defined all-recombinant protein culture system for long-term HSC expansion
- Develop pharmacological strategies to provide robust ex vivo human HSC maintenance and expansion
Blood stem cell availability is a major bottleneck in bone marrow transplantation, a curative therapy for numerous blood diseases. Blood stem cells currently cannot be stably maintained outside the body. Stable culture conditions would therefore increase blood stem cell availability, and improve accessibility to clinical bone marrow transplantation and related gene therapies. This research will ultimately improve bone marrow transplantation and related gene therapies for patients in California.
Publications
- Nat Protoc (2020) Long-term ex vivo expansion of mouse hematopoietic stem cells. (PubMed: 31915389)
- Exp Hematol (2019) Use of polyvinyl alcohol for chimeric antigen receptor T-cell expansion. (PubMed: 31874780)
- Development (2019) Hematopoietic stem cell-independent hematopoiesis and the origins of innate-like B lymphocytes. (PubMed: 31371526)
- Nature (2019) Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation. (PubMed: 31142833)
- Exp Hematol (2018) Branched-chain amino acid depletion conditions bone marrow for hematopoietic stem cell transplantation avoiding amino acid imbalance-associated toxicity. (PubMed: 29705267)
- Science (2016) Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation. (PubMed: 27934766)