Rapamycin enhances long-term hematopoietic reconstitution of ex vivo expanded mouse hematopoietic stem cells by inhibiting senescence.

ABSTRACT:

Background

The mammalian target of rapamycin (mTOR) is an important regulator of hematopoietic stem cell (HSC) self-renewal and its overactivation contributes to HSC premature exhaustion in part via induction of HSC senescence. Inhibition of mTOR with rapamycin has the potential to promote long-term hematopoiesis of ex vivo expanded HSCs to facilitate the clinical application of HSC transplantation for various hematologic diseases.

Methods

A well-established ex vivo expansion system for mouse bone marrow HSCs was used to investigate whether inhibition of overactivated mTOR with rapamycin can promote long-term hematopoiesis of ex vivo expanded HSCs and to elucidate the mechanisms of action of rapamycin.

Results

HSC-enriched mouse bone marrow LSK cells exhibited a time-

SUBMITTER: Luo Y 

PROVIDER: S-EPMC3877183 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature