RETINOIC ACID PROMOTE THE EXPANSION OF HEMATOPOIETIC STEM CELL.

1.2
#8-OR
RETINOIC ACID PROMOTE THE EXPANSION OF HEMATOPOIETIC STEM CELL.
Guan-lin Sun M.D. , Si-guo Hao PhD and Hui-Ren Chen PhD . Shanghai China, Shanghai Institute of Hematology, 200025, Rui-Jin Hospital,Shanghai Second Medical University .

The amount of hematopoietic stem cell (HSC) is one of the most critical factors for determining the curative effects of HSC transplantation. During treatment with All-trans retinoic acid (ATRA), the patients with acute promylocytic leukemia occur leukocytosis. It suggested ATRA may have potential effect on hematogenesis. A serial of experiments have been performed in vivo and vitro to study the effect of ATRA on hematogenesis. In vivo , we found that the oral administration of ATRA to BALB/C mice at a dose 15mg/kg daily could result in time-dependent hematologic changes: the peripheral blood cell counts were increased. Particularly, WBC count elevated earlier and the peak reached at day 16 (180% of control). It could enhance the amounts of CFC (CF;U-S, CFU-GM) of bone marrow of mice. In vitro, we collected enriched CD 133+ cells from human cord blood by MACS. The CD 133+ cells may be a group of HSC or primitive progenitor cell (PC). The CD 133+ cells with 8 cytokines were grown in liquid suspension culture without ATRA (control group) or with ATRA (10^-6M/L--10^-10M/L, experiment group). The results showed the amount of nucleated cell , subsets of CD 133+ , CD 34+, and CD 34+ CD 38- cells, the colonies of HPP-CFC, CFU-MIX and CFU-GM from all groups with ATRA were higher than that of control group at each interval . Gene profiles of CD 133+ cells without and with ATRA(10^-6M/L) at day 6 were detected using cDNA array U133A(Affymetrix). The results showed 624 genes were upregulated and 512 genes were downregulated. Among them, the genes are correlation to proliferation of HSPC such as CSF3-R, SCF, FLT3, IL-6R, IL-8, and STAT1, HOXB2 etc. The genes of TNF, IFN, TGF-b inhibiting proliferation of HSPC were downregulated. In summary, ATRA could stimulate the proliferation of HSPC. It suggested ATRA may be helpful for vitro expansion of HSPC.