Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis

Glia. 2009 Aug 15;57(11):1192-203. doi: 10.1002/glia.20841.


Cell-based therapies are attractive approaches to promote myelin repair. Recent studies demonstrated a reduction in disease burden in mice with experimental allergic encephalomyelitis (EAE) treated with mouse mesenchymal stem cells (MSCs). Here, we demonstrated human bone marrow-derived MSCs (BM-hMSCs) promote functional recovery in both chronic and relapsing-remitting models of mouse EAE, traced their migration into the injured CNS and assayed their ability to modulate disease progression and the host immune response. Injected BM-hMSCs accumulated in the CNS, reduced the extent of damage and increased oligodendrocyte lineage cells in lesion areas. The increase in oligodendrocytes in lesions may reflect BM-hMSC-induced changes in neural fate determination, since neurospheres from treated animals gave rise to more oligodendrocytes and less astrocytes than nontreated neurospheres. Host immune responses were also influenced by BM-hMSCs. Inflammatory T-cells including interferon gamma producing Th1 cells and IL-17 producing Th17 inflammatory cells and their associated cytokines were reduced along with concomitant increases in IL-4 producing Th2 cells and anti-inflammatory cytokines. Together, these data suggest that the BM-hMSCs represent a viable option for therapeutic approaches.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / physiology
  • Brain / immunology
  • Brain / physiopathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Encephalomyelitis, Autoimmune, Experimental / therapy*
  • Female
  • Humans
  • Interleukin-17 / metabolism
  • Interleukin-4 / metabolism
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / physiopathology
  • Multiple Sclerosis / therapy*
  • Oligodendroglia / physiology
  • Spinal Cord / immunology
  • Spinal Cord / physiopathology
  • T-Lymphocytes / physiology
  • Th1 Cells / physiology
  • Th2 Cells / physiology*


  • Cytokines
  • Interleukin-17
  • Interleukin-4