Mesenchymal Stem Cells (MSCs): A Novel Therapy for Type 2 Diabetes

Figure 2

(a) Possible mechanisms of action for MSCs on insulin target organs to alleviate insulin resistance. Exosomal miR-29b-3p can regulate cellular insulin sensitivity via SIRT-1. Furthermore, NLRP3 formation can be inhibited through immune response regulation mediated by MSCs, thus enhancing the function of IRS-1 and GLUT4 in hepatic cells. MSCs also facilitate the inhibition of MG53, which is an E3 ligase that promotes the ubiquitinoylation of IRS-1 in skeletal muscles. (b) Possible mechanisms of action for MSCs to regulate systemic inflammation. IL-1β and TNF-α secreted by the T2DM islet will stimulate MSCs to secrete IL-1Ra, which in turn ameliorates islet inflammation. MSCs can also promote the proliferation of Treg cells, and IL-10 and IL-13 secreted by Treg seem to play a key role in islet regeneration by reducing systemic inflammation. Besides, classically activated macrophages (M1) could stimulate MSCs to overexpress IL-6 and MCP-1, thus converting M1 into an alternatively activated phenotype (M2) to reduce systemic inflammation. Abbreviations: SIRT-1: sirtuin-1; NLRP3: NOD-like receptor protein 3; IRS-1: insulin receptor substrate-1; GLUT4: glucose transporter 4; MG53: Mitsugumin 53; Treg: regulatory T; TGF-β: transforming growth factor-β; MCP-1: monocyte chemoattractant protein-1; IL: interleukin; TNF-α: tumor necrosis factor-α.