Human foreskin fibroblasts exert immunomodulatory properties by a different mechanism to bone marrow stromal/stem cells.

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Wada N, Bartold PM, Gronthos S

Human foreskin fibroblasts exert immunomodulatory properties by a different mechanism to bone marrow stromal/stem cells.

Stem Cells Dev. 2011 Apr;20(4):647-59. doi: 10.1089/scd.2010.0246. Epub 2010 Oct 12.

PubMed ID
20712449 [ View in PubMed
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Abstract

Human bone marrow mesenchymal stromal/stem cells (BMSCs) have been reported to possess immunomodulatory functions with the capacity to suppress immune reactions partly mediated by immunosuppressive factors, indoleamine 2,3-dioxygenase and nitric oxide, and suggested to be potentially applicable for therapeutic use. More recently, other fibroblast-like cells have been reported to possess similar properties. Here we demonstrate that human foreskin fibroblasts (HFFs) express an MSC-like immunophenotype and possess immunosuppressive properties similar to BMSCs but lack the capacity for osteogenic and adipogenic differentiation. HFFs suppressed human peripheral blood mononuclear cells (PBMC) proliferation stimulated with mitogen or in an allogeneic mixed lymphocyte reaction comparable to BMSCs. However, HFFs showed undetectable levels of indoleamine 2,3-dioxygenase and inducible nitric oxide synthase expression, in contrast to BMSCs when cocultured with activated PBMCs. To identify HFF specific immunosuppressive factors, we performed array profiling of common cytokines expressed by HFFs and BMSCs alone or when cocultured with activated PBMCs. Real-time polymerase chain reaction analysis confirmed that multiple factors were upregulated in HFFs cocultured with activated PBMCs compared with HFFs alone or BMSCs cultured under the same conditions. Functional assays identified interferon-alpha as the major immunosuppressive mediator expressed by HFFs. These results suggest that the HFFs possess immunosuppressive properties, which are mediated by alternate mechanisms to that reported for BMSCs.

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