TITLE:
Multipotentialmesenchymal Stromal Cells (MMSC) Ameliorate Graft versus Host Disease (GVHD) in a Mouse Model, But Major Suppression of GVHD Permits Leukemic Relapse
AUTHORS:
Barbara J. O’Kane, Marcel D. DeVetten, John J. Jackson, Jordan P. Lacy, Tracy L. Farrell, John G. Sharp
KEYWORDS:
Mesenchymal Stem Cells, GVHD, Leukemia, Mouse Model
JOURNAL NAME:
Stem Cell Discovery,
Vol.4 No.2,
April
25,
2014
ABSTRACT:
A significant
complication in allogeneic stem cell transplantation is graft versus host
disease (GVHD). The use of multipotential mesenchymal stem cells (MMSC) for the
amelioration of GVHD has shown promise as a therapeutic intervention. Given
that MMSC can suppress allogeneic immune responses, there is a concern that
using these cells may promote leukemic relapse. We describe a murine model of
GVHD in the presence of leukemic cells (L1210). Acute GVHD was induced in DBA
mice by transplanting bone marrow and spleen cells from C57Bl/6J mice with or
without prior injection of L1210 cells. The recipient mice were monitored for
signs of GVHD. The mice were then treated with primary MMSC or a C57Bl bone
marrow derived cloned mesenchymal cell line (OMA-AD). The results without L1210
cells, demonstrated that mice treated with primary MMSC that had developed
moderate GVHD had increased long-term survival when compared to controls. The
group treated with OMA-AD cells showed minimal GVHD so cloned OMA-AD MMSC cells
provided a significant protective effect against GVHD, and the survival rate
was superior to that of animals treated with primary MMSC on the same day. In
the presence of L1210, the control mice all died by day 11, and the mice
receiving OMA-AD and L1210 cells died by day 9. Both had minimal GVHD. Only the
mice receiving primary MMSC that developed moderate to severe GVHD survived
long term. It appears that although MMSC and OMA-AD cells can ameliorate GVHD; the
greater immunosuppressive effect of OMA-AD cells permitted the re-growth of the
leukemic cells. In contrast, the moderate GVHD that remained after primary MMSC
treatment eliminated the leukemia in the majority of mice. These studies
demonstrated that in the mouse model, as in man, administration of primary or
cloned MMSC ameliorated GVHD. However, complete suppression of GVHD permitted
leukemic relapse.