Abstract
Background aims
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 × 106, intermediate, 1 × 106, and high, 2 × 106) with a consistent splenocyte dose (1 × 106) 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.
Key Words
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Article info
Publication history
Accepted:
November 20,
2009
Received:
August 11,
2009
Identification
Copyright
© 2010 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
