51. Valproic acid affects the engraftment of TPO-expanded cord blood cells in NOD/SCID mice.
- Author
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Vulcano F, Milazzo L, Ciccarelli C, Barca A, Agostini F, Altieri I, Macioce G, Di Virgilio A, Screnci M, De Felice L, Giampaolo A, and Hassan HJ
- Subjects
- Animals, Antigens, CD34 metabolism, Cells, Cultured, Drug Synergism, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells metabolism, Humans, Infant, Newborn, Mice, Mice, Inbred NOD, Mice, SCID, Primary Cell Culture methods, Time Factors, Treatment Outcome, Cell Proliferation drug effects, Cord Blood Stem Cell Transplantation methods, Fetal Blood cytology, Fetal Blood drug effects, Hematopoietic Stem Cells drug effects, Thrombopoietin pharmacology, Valproic Acid pharmacology
- Abstract
Hematopoietic stem and progenitor cells (HSPC) can improve the long-term outcome of transplanted individuals and reduce the relapse rate. Valproic acid (VPA), an inhibitor of histone deacetylase, when combined with different cytokine cocktails, induces the expansion of CD34+ cell populations derived from cord blood (CB) and other sources. We evaluated the effect of VPA, in combination with thrombopoietin (TPO), on the viability and expansion of CB-HSPCs and on short- and long-term engraftability in the NOD/SCID mouse model. In vitro, VPA+TPO inhibited HSPC differentiation and preserved the CD34+ cell fraction; the self-renewal of the CD34+ TPO+VPA-treated cells was suggested by the increased replating efficiency. In vivo, short- and long-term engraftment was determined after 6 and 20 weeks. After 6 weeks, the median chimerism percentage was 13.0% in mice transplanted with TPO-treated cells and only 1.4% in those transplanted with TPO+VPA-treated cells. By contrast, after 20 weeks, the engraftment induced by the TPO+VPA-treated cells was three times more effective than that induced by TPO alone, and over ten times more effective compared to the short-term engraftment induced by the TPO+VPA-treated cells. The in vivo results are consistent with the higher secondary plating efficiency of the TPO+VPA-treated cells in vitro., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2012
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