Inhibition of T cell protein tyrosine phosphatase enhances interleukin-18-dependent hematopoietic stem cell expansion.

ABSTRACT: The clinical application of hematopoietic progenitor cell-based therapies for the treatment of hematological diseases is hindered by current protocols, which are cumbersome and have limited efficacy to augment the progenitor cell pool. We report that inhibition of T-cell protein tyrosine phosphatase (TC-PTP), an enzyme involved in the regulation of cytokine signaling, through gene knockout results in a ninefold increase in the number of hematopoietic progenitors in murine bone marrow (BM). This effect could be reproduced using a short (48 hours) treatment with a pharmacological inhibitor of TC-PTP in murine BM, as well as in human BM, peripheral blood, and cord blood. We also demonstrate that the ex vivo use of TC-PTP inhibitor only provides a temporary effect on stem cells and did not alt

SUBMITTER: Bourdeau A 

PROVIDER: S-EPMC3593175 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature