Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

Abstract

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models. Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration, namely trophic factor deprivation and neuroinflammation. Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement. However, little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system. Here, we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system, focusing on recent work in the retina and the importance of the type of transplantation.

Keywords: adaptive immunity; cell therapy; central nervous system; immune system; innate immunity; mesenchymal stromal cells; neuroregeneration; preclinical studies; retina; transplantation.

Figure 1

Summary of MSC and immune system crosstalk. Graphical scheme that summarizes the interaction of MSCs with innate immune cells (yellow arrows) and adaptive immune cells (green arrows). BAX: Bcl-2 associated to X gen; CD: cluster of differentiation; CXCL: chemokine (C-X-C motif); DCs: dendritic cells; HLA: human leukocyte antigen; IDO: indoleamine-2.3-dioxygenase; IL: interleukin; IRAK-1: interleukin-1 receptor-associated kinase 1; MIF: macrophage inhibitory factor; MIP: macrophage inflammatory protein; MSC: mesenchymal stromal cell; NK: natural killer; TGF-β: transforming growth factor-β; Treg: regulatory T cell; Th: helper T cell; PGE2: prostaglandin E2; ULBP3: UL16 binding protein-3. Partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license.