We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Epigenetic reprogramming induces the expansion of cord blood stem cells.
- Authors
Chaurasia, Pratima; Gajzer, David C.; Schaniel, Christoph; D'Souza, Sunita; Hoffman, Ronald
- Abstract
Cord blood (CB) cells that express CD34 have extensive hematopoietic capacity and rapidly divide ex vivo in the presence of cytokine combinations; however, many of these CB CD34+ cells lose their marrow-repopulating potential. To overcome this decline in function, we treated dividing CB CD34+ cells ex vivo with several histone deacetylase inhibitors (HDACIs). Treatment of CB CD34+ cells with the most active HDACI, valproic acid (VPA), following an initial 16-hour cytokine priming, increased the number of multipotent cells (CD34+CD90+) generated; however, the degree of expansion was substantially greater in the presence of both VPA and cytokines for a full 7 days. Treated CD34+ cells were characterized based on the upregulation of pluripotency genes, increased aldehyde dehydrogenase activity, and enhanced expression of CD90, c-Kit (CD117), integrin α6 (CD49f), and CXCR4 (CD184). Furthermore, siRNA-mediated inhibition of pluripotency gene expression reduced the generation of CD34+CD90+ cells by 89%. Compared with CB CD34+ cells, VPA-treated CD34+ cells produced a greater number of SCID-repopulating cells and established multilineage hematopoiesis in primary and secondary immune--deficient recipient mice. These data indicate that dividing CB CD34+ cells can be epigenetically reprogrammed by treatment with VPA so as to generate greater numbers of functional CB stem cells for use as transplantation grafts.
- Subjects
CORD blood; STEM cell research; CD34 antigen; EPIGENESIS; BLOOD cells
- Publication
Journal of Clinical Investigation, 2014, Vol 124, Issue 6, p2378
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI70313