Human umbilical cord blood-derived stromal cells prevent graft-versus-host disease in mice following haplo-identical stem cell transplantation.
OBJECTIVE
Human umbilical cord blood-derived stromal cells (hUCBDSC) comprise a novel population of CD34(+) cells that has been isolated in our laboratory. They have been shown previously not only to be non-immunogenic but also to exert immunosuppressive effects on xenogenic T cells in vitro. This study investigated the role of hUCBDSC in immunomodulation in an acute graft-versus-host disease (GvHD) mouse model after haplo-identical stem cell transplantation.


METHODS
Acute GvHD was induced in recipient (B6 × BALB/c)F(1) mice by irradiation (750 cGy) followed by infusion of bone marrow cells and splenocytes from donor C57BL/6 mice. hUCBDSC were co-transplanted in the experimental group. The survival time, body weight and clinical and histopathologic scores were recorded after transplantation. The expression of surface markers [major histocompatibility complex (MHC) I, MHC II, CD80 and CD86] on CD11c(+) dendritic cells (DC), and the percentage of CD4(+) regulatory T cells (Treg), in the spleens of recipient mice were examined by flow cytometry.


RESULTS
The survival time was significantly prolonged, and the clinical and histopathologic scores were reduced in mice co-transplanted with hUCBDSC. The expression levels of the surface markers on DC were significantly lower in mice transplanted with hUCBDSC compared with those without. The proportion of CD4(+) Treg in the spleen was also increased in mice transplanted with hUCBDSC.


CONCLUSIONS
These results from a GvHD mouse model are in agreement with previous in vitro findings, suggesting that hUCBDSC possess immunosuppressive properties and may act via influencing DC and CD4(+) Treg.
Hao
Lei
L
Department of Hematology, Xinqiao Hospital, Chongqing, China.
Gao
Lei
L
Chen
Xing-Hua
XH
Zou
Zhong-Min
ZM
Zhang
Xi
X
Kong
Pei-Yan
PY
Zhang
Cheng
C
Peng
Xian-Gui
XG
Sun
Ai-Hua
AH
Wang
Qing-Yu
QY
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology*; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D033581:Stem Cell Transplantation; D017154:Stromal Cells / Q000166:cytology* / Q000637:transplantation*; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology
D015415:Biomarkers