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Version of Record online: 12 FEB 2013
Copyright © 2012 AlphaMed Press
Volume 31, Issue 2, pages 293–304, February 2013
How to Cite
Bourdeau, A., Trop, S., Doody, K. M., Dumont, D. J. and Tremblayef, M. L. (2013), Inhibition of T Cell Protein Tyrosine Phosphatase Enhances Interleukin-18-Dependent Hematopoietic Stem Cell Expansion. STEM CELLS, 31: 293–304. doi: 10.1002/stem.1276
Author contributions: A.B.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; S.T. and K.M.D.: collection and/or assembly of data, data analysis and interpretation, manuscript writing; D.J.D.: data interpretation, manuscript writing; and M.L.T.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS November 8, 2012.
- Issue online: 12 FEB 2013
- Version of Record online: 12 FEB 2013
- Accepted manuscript online: 8 NOV 2012 06:54AM EST
- Manuscript Accepted: 11 OCT 2012
- Manuscript Received: 10 APR 2012
- Lymphoma Foundation
- Jeanne and Jean-Louis Lévesque Chair in Cancer Research
- Canadian Cancer Society
Vol. 31, Issue 6, 1224, Version of Record online: 22 MAY 2013
- Protein tyrosine phosphatase;
- Stem cells;
- Progenitor cells;
- Small molecule inhibitor;
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 alter their capacity to reconstitute all hematopoietic components in vivo. We establish that one of the mechanisms whereby inhibition of TC-PTP mediates its effects involves the interleukin-18 (IL-18) signaling pathway, leading to increased production of IL-12 and interferon-gamma by progenitor cells. Together, our results reveal a previously unrecognized role for IL-18 in contributing to the augmentation of the stem cell pool and provide a novel and simple method to rapidly expand progenitor cells from a variety of sources using a pharmacological compound. STEM CELLS2013;31:293–304