Abstract 4703

Objective:

The purpose of this study was to investigate the therapeutic potential of Human umbilical cord mesenchymal stem cells (HUCMSCs) from normal donors for preventing acute GVHD following allogeneic bone marrow transplantation (BMT).

Methods:

In this study, a new method of separating and culturing HUCMSCs was used. The human umbilical cord tissue was digested by collagenase II for 2h. And after being passaged to P3, more HUCMSCs could be obtained. In the control group, after being lethally irradiated, DBA/2(H-2Kd) mice were transferred bone marrow (BM) and splenocytes (SC) from C57BL/6 (H-2Kb) mice. Recipients in the HUCMSCs-treated group were adoptive transferred HUCMSCs, BM and SC at day 0 and were transferred only HUCMSCs at day 3 again. The two groups were compared in weight, survival, histopathological specimens, lymphocyte subgroups and serum cytokine analysis.

Results:

In vitro, IFN-γ treated HUCMSCs have a strong inhibitory effect on the proliferation of CD4 + T cells (P<0.05), but untreated HUCMSCs cannot obviously inhibit the proliferation of CD4 + T cells (P>0.05). IDO is involved in the immunosuppression of HUCMSCs. In the HUCMSCs-treated group, 50% of the mice survived over 30 days after BMT, but in the control group all mice died within 18 days. The mice treated with HUMSCs exhibited light symptoms of aGVHD after day 14. There were higher IFN-γ and IL-12 levels by day 7 in serum of mice that received HUCMSCs compared to those without HUCMSCs-treatment, while the IL-4 levels showed no significant difference between the two groups. The proportion of CD3+NK1.1+NKT cells in splenocytes of HUCMSCs-treated group is higher in day 21 compared with in day 7.

Conclusion:

Using the new method of digesting human umbilical cord tissue by collagenase II for 2h, we obtained stable and pure HUCMSCs. IDO is involved in the immunosuppression of HUCMSCs. After the xenogeneic transplantation of HUCMSCs to the aGVHD model of mice, HUCMSCs can regulate cytokines such as IFN-γ, IL-12 to increase CD3+NK1.1+NKT cells.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
bone marrow transplantation, allogeneic, graft-versus-host disease, mice, stem cell, mesenchymal, umbilical cord, collagenase, cytokine, interleukin-12, therapeutic immunosuppression, graft-versus-host disease, acute

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2010 by The American Society of Hematology
2010
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