Valproic acid affects the engraftment of TPO-expanded cord blood cells in NOD/SCID mice.
Exp Cell Res
; 318(4): 400-7, 2012 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-22166516
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombopoetina
/
Células-Tronco Hematopoéticas
/
Ácido Valproico
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Transplante de Células-Tronco de Sangue do Cordão Umbilical
/
Proliferação de Células
/
Sangue Fetal
Tipo de estudo:
Evaluation_studies
Limite:
Animals
/
Humans
/
Newborn
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Itália