Abstract

Innate and Adaptive Immune Modulation by MSC Small Extracellular Vesicles

Sai Kiang Lim, Research Director, A*STAR Institute of Medical Biology

Mesenchymal stromal cell (MSC) is the most clinically tested cell type for regenerative medicine.  It has significant immunomodulatory potency as evidenced by recent market approval for use in GVHD and Crohn’s disease.  It exerts at least part of this potency through secreted small extracellular vesicles of 50 to 200 nm diameter.  We have previously shown that MSC-sEVs have both innate and adaptive immunomodulatory activities.  They activated TLR4 in monocytes to elicit an anti-inflammatory cytokine secretion profile that was different from the pro-inflammatory profile elicited by LPS-mediated TLR4 activation.  The TLR4 activation by MSC-sEVs was neutralized by a blocking antibody against EDA-containing fibronectin, a TLR4 ligand that is present in MSC-sEV preparations.  MSC-sEVs also induced mouse CD4+CD25+ T cells or CD4+CD25+Foxp3+ Tregs from CD4+ T cells activated by allogeneic APC-enriched CD11C+ cells but not those activated by anti-CD3/CD28 mAbs. This induction was MSC-sEV and APC dose–dependent.