Mesenchymal stromal cells inhibit graft-versus-host disease of mice in a dose-dependent manner.
OBJECTIVE
Graft-versus-host disease (GvHD) remains a major complication after allogeneic hematopoietic cell transplantation (HCT). Recent literature demonstrates a potential benefit of human mesenchymal stromal cells (MSC) for the treatment of refractory GvHD; however, the optimal dose remains uncertain. We set out to develop an animal model that can be used to study the effect of MSC on GvHD.


METHODS
A GvHD mouse model was established by transplanting C3H/he donor bone marrow (BM) cells and spleen cells into lethally irradiated BALB/c recipient mice. MSC were obtained from C3H/he mice and the C3H/10T1/2 murine MSC line.


RESULTS
The mRNA expression of Foxp3 in regional lymph nodes (LN) localized with T cells was markedly increased by the addition of C3H10T1/2 cells in a real-time polymerase chain reaction (PCR). Using a mixed lymphocyte reaction, we determined the optimal splenocyte proliferation inhibition dose (MSC:splenocyte ratios 1:2 and 1:1). Three different C3H10T1/2 cell doses (low, 0.5 x 10(6), intermediate, 1 x 10(6), and high, 2 x 10(6)) with a consistent splenocyte dose (1 x 10(6)) were evaluated for their therapeutic potential in an in vivo GvHD model. The clinical and histologic GvHD score and Kaplan-Meier survival rate were improved after MSC transplantation, and these results demonstrated a dose-dependent inhibition.


CONCLUSIONS
We conclude that MSC inhibit GvHD in a dose-dependent manner in this mouse model and this model can be used to study the effects of MSC on GvHD.
Joo
Sun-Young
SY
Department of Microbiology, Ewha Womans University School of Medicine, Ewha Medical Research Center, Seoul, Korea.
Cho
Kyung-Ah
KA
Jung
Yun-Jae
YJ
Kim
Han-Seong
HS
Park
Seong-Yeol
SY
Choi
Yong-Bock
YB
Hong
Kyeong-Man
KM
Woo
So-Youn
SY
Seoh
Ju-Young
JY
Cho
Su Jin
SJ
Ryu
Kyung-Ha
KH
D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000502:physiology; D018920:Coculture Techniques; D005260:Female; D006086:Graft vs Host Disease / Q000473:pathology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D053208:Kaplan-Meier Estimate; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013154:Spleen / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*