Utility of co-transplanting mesenchymal stem cells in islet transplantation

Figure 1 Immunomodulatory effect of mesenchymal stem cells (modified and quoted from Uccelli et al[13]). Mesenchymal stem cells (MSCs) can inhibit the proliferation and cytotoxicity of resting natural killer (NK) cells via the generation of mediators, including prostaglandin E₂ (PGE₂), indoleamine 2,3-dioxygenase (IDO) and soluble human leukocyte antigen (sHLA)-G5; MSCs inhibit the differentiation of monocyte to antigen presenting dendritic cells (DCs). MSCs also inhibit TNF-α production by DCs and upregulate IL-10 production by plasmacytoid DCs (pDCs): effects modulated by PGE₂; MSCs directly inhibit CD4⁺ T cell, CD8⁺ T cell, and B cells that are involved in allogeneic cell rejection by releasing PGE₂, IDO, or sHLA-G5. CD4⁺ T cell inhibition limits B cell proliferation and antibody production whilst CD8⁺ T cell inhibition prevents cytotoxicity. MSCs induce generation of immunomodulatory regulatory T cells that suppress immune activation, help to maintain homeostasis, and promote self tolerance by production of IL-10 from pDCs and by releasing HLA-G5. Thus, MSCs can promote immunotolerance and facilitate the engraftment of allogeneic islets.