Human umbilical cord blood-derived stromal cells prevent graft-versus-host disease in mice following haplo-identical stem cell transplantation

Abstract

Background aims. Human umbilical cord blood-derived stromal cells (hUCBDSC) comprise a novel population of CD34⁺ cells that has been isolated in our laboratory. They have been shown previously not only to be non-immunogenic but also to exert immunosuppressive effects on xenogenic T cells in vitro. This study investigated the role of hUCBDSC in immunomodulation in an acute graft-versus-host disease (GvHD) mouse model after haplo-identical stem cell transplantation. Methods. Acute GvHD was induced in recipient (B6 × BALB/c)F₁ mice by irradiation (750 cGy) followed by infusion of bone marrow cells and splenocytes from donor C57BL/6 mice. hUCBDSC were co-transplanted in the experimental group. The survival time, body weight and clinical and histopathologic scores were recorded after transplantation. The expression of surface markers [major histocompatibility complex (MHC) I, MHC II, CD80 and CD86] on CD11c⁺ dendritic cells (DC), and the percentage of CD4⁺ regulatory T cells (Treg), in the spleens of recipient mice were examined by flow cytometry. Results. The survival time was significantly prolonged, and the clinical and histopathologic scores were reduced in mice co-transplanted with hUCBDSC. The expression levels of the surface markers on DC were significantly lower in mice transplanted with hUCBDSC compared with those without. The proportion of CD4⁺ Treg in the spleen was also increased in mice transplanted with hUCBDSC. Conclusions. These results from a GvHD mouse model are in agreement with previous in vitro findings, suggesting that hUCBDSC possess immunosuppressive properties and may act via influencing DC and CD4⁺ Treg.

Key Words::

• graft-versus-host disease
• haplo-identical stem cell transplantation
• regulatory T cell
• stromal cell
• umbilical cord blood

Acknowledgments

This work was supported by the Chinese National Natural Science Foundation (numbers 30971109 and 30670890), the Chongqing Natural Science Foundation (CSTC2009BA5011), the Chongqing Key Discipline of Medical Science (number 2006C028) and the 1520 Foundation.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.