期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 124, 期 6, 页码 2378-2395出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI70313
关键词
-
资金
- NYSTEM [C026431]
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 alpha 6 (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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据