Methods and compositions relating to hematopoietic stem cell expansion, enrichment, and maintenance
AssigneesChildren's Medical Center Corporation, President and Fellows of Harvard College
InventorsDerrick J. Rossi, Wataru Ebina, Morag Stewart, Paula Gutierrez-Martinez, Lee L. Rubin, Lance Davidow
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Abstract
The methods and compositions described herein relate to producing, expanding, enriching, and/or maintaining hematopoietic stem cells ex vivo by treating the cells with an agent(s) that exhibits two or more activities selected from modulation of histone methylation; inhibition of TGFβ signaling; inhibition of p38 signaling; activation of canonical Wnt signaling; and modulation of histone acetylation. In some embodiments, the technology described herein relates to transplantation of hematopoietic stem cells.
Claims21
A method of producing an expanded population of hematopoietic stem cells ex vivo, said method comprising contacting a population of hematopoietic stem cells with one or more agents that together exhibit the activities of:
- a. modulation of histone methylation;
- b. inhibition of TGFβ signaling;
- and
- c. modulation of histone acetylation,
- wherein the one or more agents are present in amounts that are sufficient to produce an expanded population of hematopoietic stem cells.
A composition comprising one or more agents that together exhibit the activities of:
- a. modulation of histone methylation;
- b. inhibition of TGFβ signaling;
- and
- c. modulation of histone acetylation.
Dependencies are inferred from the claim text.