Optimizing self-renewal signaling kinetics to stabilize ex vivo hematopoietic stem cell expansion
Grant Award Details
Grant Type:
Grant Number:
DISC1-10555
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$210,906
Status:
Closed
Grant Application Details
Application Title:
Optimizing self-renewal signaling kinetics to stabilize ex vivo hematopoietic stem cell expansion
Public Abstract:
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
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
Statement of Benefit to California:
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
- 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)
- Development (2019): Hematopoietic stem cell-independent hematopoiesis and the origins of innate-like B lymphocytes. (PubMed: 31371526)
- Nat Protoc (2020): Long-term ex vivo expansion of mouse hematopoietic stem cells. (PubMed: 31915389)
- Nature (2019): Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation. (PubMed: 31142833)
- Exp Hematol (2019): Use of polyvinyl alcohol for chimeric antigen receptor T-cell expansion. (PubMed: 31874780)
