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Tissue-Specific Stem Cells
Article first published online: 19 DEC 2012
Copyright © 2012 AlphaMed Press
Volume 31, Issue 1, pages 156–166, January 2013
How to Cite
Mizrahi, K., Stein, J., Yaniv, I., Kaplan, O. and Askenasy, N. (2013), TNF-α Has Tropic Rather than Apoptotic Activity in Human Hematopoietic Progenitors: Involvement of TNF Receptor-1 and Caspase-8. STEM CELLS, 31: 156–166. doi: 10.1002/stem.1259
Author contributions: K.M.: performance of experiments and collection of data; J.S. and I.Y.: collection of data and data analysis and interpretation; O.K.: collection of data and manuscript writing; N.A.: performance of experiments, conception and design, and manuscript writing.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS October 18, 2012.
- Issue published online: 19 DEC 2012
- Article first published online: 19 DEC 2012
- Accepted manuscript online: 18 OCT 2012 07:34AM EST
- Manuscript Accepted: 25 SEP 2012
- Manuscript Received: 13 APR 2012
- Frankel Trust for Experimental Bone Marrow Transplantation
- Adult hematopoietic stem cells;
- Tumor necrosis factor;
- Umbilical cord blood;
- Mobilized peripheral blood
Tumor necrosis factor-α (TNF-α) has been suggested to exert detrimental effects on hematopoietic progenitor function that might limit the success of transplants. In this study, we assessed the influences of TNF-α and its two cognate receptors on the function of fresh umbilical cord blood (UCB) and cryopreserved mobilized peripheral blood (mPB). CD34+ progenitors from both sources are less susceptible to spontaneous apoptosis than lineage-committed cells and are not induced into apoptosis by TNF-α. Consequently, the activity of UCB-derived severe combined immune deficiency (SCID) reconstituting cells and long-term culture-initiating cells is unaffected by this cytokine. On the contrary, transient exposure of cells from both sources to TNF-α stimulates the activity of myeloid progenitors, which persists in vivo in UCB cell transplants. Progenitor stimulation is selectively mediated by TNF-R1 and involves activation of caspase-8, without redundant activity of TNF-R2. Despite significant differences between fresh UCB cells and cryopreserved mPB cells in susceptibility to apoptosis and time to activation, TNF-α is primarily involved in tropic signaling in hematopoietic progenitors from both sources. Cytokine-mediated tropism cautions against TNF-α neutralization under conditions of stress hematopoiesis and may be particularly beneficial in overcoming the limitations of UCB cell transplants. Stem Cells2013;31:156–166