Mesenchymal Stem Cells - Interest Group
Immune Advantages:

Overview: Numerous studies have demonstrated
that human MSC avoid allorecognition, interfere
with dendritic cell and T-cell function and generate
a local immunosuppressive microenvironment by
secreting cytokines. It has also been shown that
the immunomodulatory function of human MSC is
enhanced when the cells are exposed to an
inflammatory environment characterised by the
presence of elevated local interferon-gamma
levels. Other studies contradict some of these
findings, reflecting both the highly heterogeneous
nature of MSC isolates and the considerable
differences between isolates generated by the
many different methods under development.

Details:

The immune phenotype of MSCs (widely described as MHC I+, MHC II–, CD40–, CD80–,
CD86–) is regarded as nonimmunogenic and, therefore, transplantation into an allogeneic host
may not require immunosuppression. MHC class I may activate T cells, but, with the absence
of costimulatory molecules, a secondary signal would not engage, leaving the T cells anergic.
Many reports have also described MSCs as having immunosuppressive properties, specifically
that MSCs can modulate many T-cell functions including cell activation. This suppression
appears to be independent of MHC matching between the MSCs and the T cells. Some reports
have demonstrated that direct cell-cell contact is required for suppression, whereas others
have shown that the suppressor activity depends on a soluble factor. It has also been shown
that MSCs have immunomodulatory properties impairing maturation and function of dendritic
cells and that hMSCs inhibit in vitro human B-cell proliferation, differentiation, and chemotaxis.

Despite some disagreement on the mechanisms by which MSCs exert their
immunosuppressive effects, there is some evidence that these in vitro observations may
translate to the in vivo setting. It has been reported that in vivo administration of baboon
MSCs in immunocompetent outbred baboons significantly prolongs the survival of MHC-
mismatched skin grafts. Also, hMSCs have been administered in vivo to improve the outcome
of allogenic transplantation by promoting hematopoietic engraftment and to hamper graft-
versus-host disease. More recently, systemic administration of murine MSCs to mice affected
by experimental autoimmune encephalomyelitis (a model of multiple sclerosis), a disease
mediated by self-reactive T cells, resulted in striking improvement in disease symptoms,
mediated by the induction of peripheral tolerance. Therefore, targeting MSCs to inflamed
tissues may have therapeutic benefit due to their immunosuppressive properties.

However, another study investigated whether the immunosuppressive properties of murine
MSCs could be of therapeutic value in the collagen-induced arthritis (CIA) mouse model (an
established model of rheumatoid arthritis) to explore the effect of MSCs on disease
progression. Interestingly, they found that MSCs offered no benefit in the CIA model of
arthritis; indeed, they found that MSCs were associated with accentuation of the Th1 response.
Experiments in vitro showed that the addition of tumor necrosis factor {alpha} (TNF{alpha})
was sufficient to reverse the immunosuppressive effect of MSCs on T-cell proliferation,
possibly accounting for the lack of improvement of CIA. Hence, nonengineered MSCs may be
unsuitable for the treatment of certain inflammatory diseases.

References:

  • Concise Review: mesenchymal stem/multipotent stromal cells: the state of
    transdifferentiation and modes of tissue repair--current views. Stem Cells. 2007 Nov;25
    (11):2896-902. Epub 2007 Sep 27. Review.

  • Ryan JM, Barry FP, Murphy JM, Mahon BP (2005). "Mesenchymal stem cells avoid
    allogeneic rejection". J Inflamm (Lond) 2: 8. doi:10.1186/1476-9255-2-8. PMID
    16045800.

  • Ryan JM, Barry F, Murphy JM, Mahon BP (2007). "Interferon-gamma does not break, but
    promotes the immunosuppressive capacity of adult human mesenchymal stem cells".
    Clin. Exp. Immunol. 149 (2): 353–63. doi:10.1111/j.1365-2249.2007.03422.x (inactive
    2008-06-22). PMID 17521318.
A murine mesenchymal stem cell cultured in
media containing known neural growth factors. It
displays a flattened cell body, extended
morphology and upregulated expression of betaIII
tubulin, a cytoskeletal protein expressed in
neurons and visualized with immunolabeling for
Texas Red.