Allogenic mesenchymal stem cell transplantation ameliorates nephritis in lupus mice via inhibition of B-cell activation

Cell Transplant. 2013;22(12):2279-90. doi: 10.3727/096368912X658692. Epub 2012 Oct 31.

Abstract

Recent evidence indicates that bone marrow-derived mesenchymal stem cells (BM-MSCs) possess immunosuppressive properties both in vitro and in vivo. We have previously demonstrated that transplantation of human MSCs can significantly improve the autoimmune conditions in MRL/lpr mice. The current study aimed to determine the mechanisms by which murine BM-MSC transplantation (MSCT) ameliorates nephritis in MRL/lpr mice. In this study, we found that MSCT can significantly prolong the survival of MRL/lpr mice. Eight weeks after transplantation, MSCT-treated mice showed significantly smaller spleens than control animals, with fewer marginal zones (MZs), T1, T2, activated B-cells, and plasma cells. Moreover, serum levels of B-cell activating factor (BAFF) and IL-10 in MSCT-treated mice decreased significantly compared to those in the control group, while levels of serum TGF-β were increased. Notably, decreased BAFF expression in both spleen and kidney was accompanied by decreased production of anti-dsDNA autoantibodies and proteinuria in MSCT-treated mice. Since BAFF is mainly expressed by T-cells and dendritic cells, we incubated BM-MSCs and DCs together and found that the production of BAFF by DCs was suppressed by MSCs. Thus, our findings suggest that MSCT may suppress the excessive activation of B-cells via inhibition of BAFF production in MRL/lpr mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Autoantibodies / metabolism
  • B-Cell Activating Factor / blood
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Bone Marrow Cells / cytology
  • Cells, Cultured
  • Female
  • Interleukin-10 / blood
  • Kidney / metabolism
  • Kidney / pathology
  • Lymphocyte Activation
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred MRL lpr
  • Nephritis / metabolism
  • Nephritis / pathology
  • Nephritis / surgery
  • Nephritis / therapy*
  • Proteinuria / diagnosis
  • Spleen / metabolism
  • Spleen / pathology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transforming Growth Factor beta / blood
  • Transplantation, Homologous

Substances

  • Autoantibodies
  • B-Cell Activating Factor
  • Transforming Growth Factor beta
  • Interleukin-10