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Mesenchymal stem cells avoid allogeneic rejection

Ryan, Jennifer M, Barry, Frank P, Murphy, J Mary, Mahon, Bernard P·2005·Journal of Inflammation
DOI 10.1186/1476-9255-2-8PMC PMC1215510
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Abstract

Adult bone marrow derived mesenchymal stem cells offer the potential to open a new frontier in medicine. Regenerative medicine aims to replace effete cells in a broad range of conditions associated with damaged cartilage, bone, muscle, tendon and ligament. However the normal process of immune rejection of mismatched allogeneic tissue would appear to prevent the realisation of such ambitions. In fact mesenchymal stem cells avoid allogeneic rejection in humans and in animal models. These finding are supported by in vitro co-culture studies. Three broad mechanisms contribute to this effect. Firstly, mesenchymal stem cells are hypoimmunogenic, often lacking MHC-II and costimulatory molecule expression. Secondly, these stem cells prevent T cell responses indirectly through modulation of dendritic cells and directly by disrupting NK as well as CD8+ and CD4+ T cell function. Thirdly, mesenchymal stem cells induce a suppressive local microenvironment through the production of prostaglandins and interleukin-10 as well as by the expression of indoleamine 2,3,-dioxygenase, which depletes the local milieu of tryptophan. Comparison is made to maternal tolerance of the fetal allograft, and contrasted with the immune evasion mechanisms of tumor cells. Mesenchymal stem cells are a highly regulated self-renewing population of cells with potent mechanisms to avoid allogeneic rejection.

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Figure 1 Human mesenchymal stem cells (MSC) are spindle shaped, fibroblast-like cells. Original magnification × 100, phase-contrast light microscopy, scale bar represents 50 μm.
Figure 1 Human mesenchymal stem cells (MSC) are spindle shaped, fibroblast-like cells. Original magnification × 100, phase-contrast light microscopy, scale bar represents 50 μm.CC BY · PubMed Central
Figure 2 Human MSC cultured according to [106, 107] are A) MHC-I positive (HLA-A,B,C, antibody W6/32-FITC), B) MHC class II negative (HLA-DR, antibody LN-3-PE); C) CD14 negative (antibody MEM-18-FITC), D) CD86 negative (antibody IT2.2-PE); and E) CD40L/ CD154 (antibody 24-31-FITC), F) CD95L (FasL) negative (antibody NOK-1-PE). Isotype matched control antibody labelling are shown as unshaded plots, FITC conjugates are shown in blue, PE conjugates shown in pink. Flow cytometry performed according to methods previously described [108-110].
Figure 2 Human MSC cultured according to [106, 107] are A) MHC-I positive (HLA-A,B,C, antibody W6/32-FITC), B) MHC class II negative (HLA-DR, antibody LN-3-PE); C) CD14 negative (antibody MEM-18-FITC), D) CD86 negative (antibody IT2.2-PE); and E) CD40L/ CD154 (antibody 24-31-FITC), F) CD95L (FasL) negative (antibody NOK-1-PE). Isotype matched control antibody labelling are shown as unshaded plots, FITC conjugates are shown in blue, PE conjugates shown in pink. Flow cytometry performed according to methods previously described [108-110].CC BY · PubMed Central
Figure 3 MSC and tumor cells create a suppressive microenvironment. There are fundamental differences between tumor cells (A) and MSC (B) with respect to control of cell division, however many mechanisms exploited by the former to evade immune deletion are also used by MSC to avoid allogeneic rejection. Details of mechanisms and associated references are supplied in the body of the text and Table 1.
Figure 3 MSC and tumor cells create a suppressive microenvironment. There are fundamental differences between tumor cells (A) and MSC (B) with respect to control of cell division, however many mechanisms exploited by the former to evade immune deletion are also used by MSC to avoid allogeneic rejection. Details of mechanisms and associated references are supplied in the body of the text and Table 1.CC BY · PubMed Central

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Metadata

Authors
Ryan, J. M., Barry, F. P., Murphy, J. M., & Mahon, B. P.
Venue
Journal of Inflammation
Publisher
Springer Science and Business Media LLC
Published
2005-07-26
Volume
2
Issue
1
ISSN
1476-9255
DOI
10.1186/1476-9255-2-8
PMC
PMC1215510
Cited by
714
References
2
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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