Immunologic Effects Of Mesenchymal Stem Cells In The Treatment Of Refractory Acute Graft-Versus-Host Disease

Mesenchymal stem cells (MSCs) have been considered as a promising strategy for the prevention and treatment of acute graft-versus-host disease (aGVHD), but the mechanism of MSCs ameliorating GVHD is still not fully understood. A few studies suggested that MSCs ameliorated GVHD via protecting and repairing the function of thymus.

Twenty refractory aGVHD patients receiving MSCs treatment were enrolled in this study, and twenty grade II to IV aGVHD patients treated without MSCs were matched as non-MSCs group. MSCs were given at a median dose of 1×10⁶ cells/kg once weekly until aGVHD got complete response (CR) or MSCs were infused for a total of 8 doses. Lymphocyte subsets of T-cell, B-cell, and NK-cell in peripheral blood were analyzed by flow cytometry before and 30, 60, 90, 180 and 360 days after the MSC infusion in MSC group and the corresponding period in the control group.

A total of the 33 patients who survived more than 30 days after the study treatments were evaluated for the alterations in cellular immune compartment and cGVHD, including 15 cases in MSCs group and 18 in non-MSCs group. In MSCs group, patients had a significantly higher CD4⁺/CD8⁺ T-cell ratio at 60, 90 and 180 day after MSCs treatments, which subsequently equalized at 360 day compared with non-MSCs group. The MSC group presented higher percentages of CD4⁺CD25⁺ regulatory T cells (Treg) comparing with non-MSCs group, especially at 90 and 180 day, and approached at 360 day. The proportion of CD4⁺CD45RO⁺ and CD4⁺CD45RA⁺ naïve T-cells in MSC group were also higher than those in non-MSCs group at 60, 90 and 180 day, but not different at 360 day. The proportion of CD19⁺ and CD16⁺CD56⁺ was not detected striking difference between the two groups. Four patients (26.7%) experienced cGVHD in MSCs group, compared with twelve (66.7%) in non-MSCs group (p=0.02).

In conclusion, our data indicate that MSCs might ameliorate aGVHD and induce longer-lasting immune tolerance by altering cellular immune compartments in peripheral blood. The alteration of the cellular immune compartments is associated with the protecting and repairing role of MSCs to thymus.

Liu:863 Program (No. 2011AA020105): Research Funding; National Public Health Grand Research Foundation (Grant No. 201202017): Research Funding; National Natural Science Foundation of China (Grant No.81000231, No.81270647): Research Funding; Science and Technology Program of Guangzhou of China (11A72121174) : Research Funding.