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

Cytotherapy. 2011 Jan;13(1):83-91. doi: 10.3109/14653249.2010.501786. Epub 2010 Jul 22.

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)F(1) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cells, Cultured
  • Fetal Blood / cytology*
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / prevention & control*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Stem Cell Transplantation*
  • Stromal Cells / cytology*
  • Stromal Cells / transplantation*
  • Survival Analysis
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Biomarkers