Methods for Stimulating Hematopoietic Stem Recovery by Inhibiting TGFβ Signaling
- 詳細技術說明
- This invention discloses methods for promoting hematopoietic recovery after myelosuppression or other hematologic stresses by administering an inhibitor of TGFβ signaling to expand hematopoietic stem and progenitor cells.
- *Abstract
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Hematopoietic stem cells (HSCs) are required for lifelong blood cell production. Normally, the majority of HSCs are deeply quiescent but during times of hematologic stress—for example after chemotherapy, bone marrow transplantation, massive infection or bleeding—HSCs undergo extensive self-renewal and differentiation to meet increased hematopoietic demands.
Cornell researchers studied the mechanism for how these processes wind down after stress. This had never been studied previously. They found that transforming growth factor-β (TGFβ) signals drive activated HSCs back to homeostasis during recovery from the stress. Blockade of TGFβ after a hematopoietic stress delayed the return of HSCs to quiescence and accelerated hematopoietic reconstitution. The outcome was faster recovery of all blood cell counts after myelosuppressive chemotherapy and faster hematopoietic engraftment after transplantation.
This discovery provides a novel approach to promote hematopoietic recovery by blocking the TGFβ signaling. This invention provides novel methods for stimulating hematopoietic regeneration by administering an inhibitor of TGFβ signaling to a subject with hematopoietic deficiencies such as after chemotherapy, hematopoietic stem cell transplant or other causes of hematopoietic stress and/or deficiency.
Potential Commercial Applications:
- Therapeutic target to stimulate recovery from myelosuppression or other causes of hematopoietic deficiency or stress.
Advantages:
- A novel target and novel methods to stimulate robust recovery of all blood lineages simultaneously including neutrophils, platelets, lymphocytes, red blood cells.
- *Licensing
- Brian J. Kellybjk44@cornell.edu212-746-6186
- 其他
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TGFβ restores hematopoietic homeostasis after myelosuppressive chemotherapy. J Exp Med, 2013, 210, 623-39.
- 國家/地區
- 美國
