Abstract 16995: Anti-Inflammatory and Immuno-Modulatory Properties of Neonatal MSC

Abstract

Background: Anti-inflammatory and immunomodulatory properties are prerequisites for the success of cell therapy as shown by adult Mesenchymal Stem cells (MSC) by reducing both B- and T-lymphocyte proliferation, in a paracrine dependent manner. Proteomics of neonatal MSCs (nMSCs) has identified the superior quality of secretome containing a significantly higher number of anti-inflammatory (68 vs 21 in aMSCs) molecules. Hypothesis: nMSCs have potent anti-inflammatory and immunomodulatory characteristics as compared to other cell types currently being used as cell therapy. Methods: nMSC were tested and compared to other cell types for: a) Hypo-immunogenicity (expression of MHCII in the presence of IFN-gamma), b) immunogenicity (reduce proliferation of human CD4+ T-cells in a co-culture mixed lymphocyte reaction (MLR), c) anti-inflammatory properties (reduce IL-8 secretion of macrophages in the presence of Nigericin, d) systematic immune response (using rat myocardial infarction (MI) model (IL10, TNF-a and IL12)) and e) Immunomodulation (CD4+ cells to T reg CD4 + /CD25 + /FoxP3 + ). Results: Expression of MHCII on nMSCs, after 72 hours of exposure to IFN-gamma and proliferation of CD4 + cells in MLR was significantly (40±3.8% and 55±4.3%, n=5) reduced as compared to aMSC or CDC. IL8 was measured in the supernatants of nMSC derived secretome reduced the secretion of IL8 from activated macrophages in a dose dependent manner (150 ug protein/ml). Intravenous injection of nMSCs in a rat MI model significantly reduced serum levels of of TNF-α and IL-12 while upregulated IL-10 and improving myocardial function. While BM-MSCs and aMSCs failed to significantly modulate immune system, nMSC significantly increased the number of Treg cells as compared to CDC. Similar results were observed with Pig IRI model. Conclusions: Together, in a head-to-head comparison, nMSCs outperformed all other competitive cell types currently under investigation for their tissue repairing role, including CDCs and BM-MSCs to achieve the highest clinical efficacy.