3',4'-Dimethoxyflavone and valproic acid promotes the proliferation of human hematopoietic stem cells

Human hematopoietic stem cells (HSCs) have been clinically used for transplantation and gene and cellular therapy for more than 4 decades. However, this use is limited because of the challenges in the ex vivo culturing of HSCs. The major hurdle is to amplify these cells without losing their self-renewing property.

In our study, we tested 3',4'-dimethoxyflavone (3'4'-DMF) and valproic acid (VPA) on the ex vivo expansion of HSCs under both normoxic (20% O2) and hypoxic (1% O2) conditions. 3'4'-DMF is a widely used anticancer drug that acts as a competitive antagonist of the aryl hydrocarbon receptor. VPA is a potent inhibitor of histone deacetylase and is used in the treatment of neurologic disorders.

Culturing HSCs (from mobilized peripheral blood) under normoxia, with 3'4'-DMF and VPA, highly preserved the CD34 positivity (3'4'-DMF, 22.1%, VPA, 20.3%) after 1 week and strongly enhanced the CD34(+) cells (3'4'-DMF, 27.8 fold; VPA, 34.1 fold) compared with the control cultures (11.6% and 14.4 fold). Addition of 3'4'-DMF and VPA also resulted in more primary colonies and replating efficiency compared with control cultures. Although no significant effect was observed on the enhancement of CD34(+) cells under hypoxia, the number of primary colonies was significantly higher than the control cultures.

Based on these findings, this study presents, for the first time, in vitro evidence for a new and relevant effect of 3'4'-DMF on human HSCs. In addition, the results suggest a potential clinical use of 3'4'-DMF and VPA in HSC therapy.