Valproic acid enhances the engraftability of human umbilical cord blood hematopoietic stem cells expanded under serum-free conditions.
Valproic acid (VPA) is a histone deacetylase inhibitor previously shown to promote the proliferation and self-renewal of CD34(+) hematopoietic cells. We tested the effect of VPA in conjunction with the selective amplification technology developed by Viacell Inc. Stem cells enriched from frozen cord blood were cultured for 7 d, subjected to reselection and grown in fresh medium for a further 7 d. Treatment with VPA resulted in an average two-fold higher expansion of CD45(+)34(+) cells compared with control. Furthermore, VPA-treatment induced higher numbers of CD45(+)34(+) cells to reside in the S phase than control cultured cells and resulted in a 2.5-fold upregulation in HOXB4 expression. Importantly, VPA-treated cells reconstituted hematopoiesis in non-obese diabetic/severe combined immunodeficient mice with a six-fold higher efficiency than control cells. Collectively, our results indicate that VPA, already used clinically for neurologic disorder treatment, is a useful additive for the ex vivo culture of hematopoietic stem/progenitor cells to enhance engraftment efficiency.
Seet
Li-Fong
LF
ViaCell Singapore Research Centre, Singapore, Republic of Singapore. seet.li.fong@seri.com.sg
Teng
Eileen
E
Lai
Yih-Shin
YS
Laning
Joseph
J
Kraus
Morey
M
Wnendt
Stephan
S
Merchav
Shosh
S
Chan
Shing Leng
SL
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D001483:Base Sequence; D002453:Cell Cycle; D016895:Culture Media, Serum-Free; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005312:Fetal Blood; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014635:Valproic Acid / Q000494:pharmacology*
D018952:Antigens, CD34; D016895:Culture Media, Serum-Free; D017931:DNA Primers; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid; D017493:Leukocyte Common Antigens