ALL-TRANS RETINOIC ACID UP-REGULATES ICAM-1 EXPRESSION AND ENHANCES
ENGRAFTMENT OF HEMATOPOIETIC STEM CELLS IN MURINE MODEL FOR UNRELATED
UMBILICAL CORD BLOOD TRANSPLANTATION
Huang S-L, Mai
H-R, Fang J-P, Wei Q, Huang W-G, Xu H-G
Hematopoietic
Stem Cell Transplantation Center, Dept. of Pediatrics, Sun Yat-sen Memorial
Hospital, Sun Yat-sen University of Medical Sciences, Guangzhou, China
Objective: To explore the effect of
all-trans retinoic acid (RA) on the expression of intercellular adhesion
molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) of bone
marrow stromal cell (BMSC) in vitro and on the engraftment of
hematopoietic stem cells (HSC) in C57BL/6/BABL/c murine model
(H-2b/H-2d) for unrelated umbilical cord blood
transplantation (UR-UCBT).
Methods: In vitro the
expressions of ICAM-1 and VCAM-1 of murine BMSC were detected by flow
cytometry and the binding capacity of umbilical cord blood mononuclear
cells (UCBMNC) to BMSC was tested by MTT assay after co-culturing with o.1μmol•L-1, 1.0μmol•L-1 and 10.0μmol•L-1 RA
respectively. 1×106 and 0.5×106 nucleated
cells (NC) of near-term fetal and neonatal murine peripheral blood (FNPB)
respectively were transfused into lethally chemotherapied (cyclophosplamide
380mg•kg-1 ,ip) recipients and 15mg•kg-1d-1
and 5mg•kg-1d-1 RA (15mg
and 5mg RA) were administrated respectively from d–2 to d+2, then the
evidence of engraftment, hematopoietic and immunologic recovery, graft
versus host disease (GVHD) and survival rate were observed.
Results: 1.0μmol•L-1 and 10.0μmol•L-1 RA
induced the expression of ICAM-1 and increased the adhesion rate of UCBMNC
to BMSC, however, RA did not induce
the expression of VCAM-1. It is positive correlation between the increment
of the ICAM-1 expression and the increment of the adhesion rate (r=0.7883,
p<0.05). H-2Db+ cells of recipient bone marrow were higher in
both 15mg and 5mg RA treated mice than those in untreated controls
(p<0.05). Hematopoietic and immunologic recovery occurred faster in
RA-treated than in untreated mice(p<0.05). Acute GVHD was absent. When 1×106 NC of FNPB
were transfused without RA, 41.67% of the mice survived 30 days
post-transplantation. The respective survival rates of mice given 15mg and
5mg RA were 72.73% and 70.83%. When 0.5×106 cells were
transfused without RA, 14.29% of the mice survived. The respective survival
rates of mice given 15mg and 5mg RA were 42.86% and 43.48%, which were
equivalent to that of transfused 1×106 cells
without RA treatment (p>0.05).
Conclusion: Our results suggest that
RA up-regulates ICAM-1 expression of BMSC and increases the adhesion of
UCBMNC to BMSC in vitro, and enhances the engraftment of HSC in
murine model for UR-UCBT, which may be helpful to improve the clinical
outcome of UCBT.