ABSTRACT
The therapeutic potential of mesenchymal stem cells (MSCs) has been heralded by their multipotentiality and immunomodulatory capacity. MSCs migrate toward sites of tissue damage, where specific pro-inflammatory factors 'license' their immunosuppressive functions. Recent studies in animal models of ocular surface disease have demonstrated the potential of MSC-derived therapies to limit inflammation and promote tissue repair. Herein, we review the immunoregulatory mechanisms of MSCs, as well as strategies to harness their regenerative function at the cornea. We examine reports of the therapeutic application of MSCs in the setting of ocular surface inflammation; including corneal injury, transplantation, ocular surface autoimmunity and allergy.
Subject(s)
Autoimmunity , Corneal Injuries/surgery , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/immunology , Animals , Corneal Injuries/immunology , HumansABSTRACT
Mesenchymal stem cells (MSCs) possess distinct immunomodulatory properties and have tremendous potential for use in therapeutic applications in various inflammatory diseases. MSCs have been shown to regulate pathogenic functions of mature myeloid inflammatory cells, such as macrophages and neutrophils. Intriguingly, the capacity of MSCs to modulate differentiation of myeloid progenitors (MPs) to mature inflammatory cells remains unknown to date. Here, we report the novel finding that MSCs inhibit the expression of differentiation markers on MPs under inflammatory conditions. We demonstrate that the inhibitory effect of MSCs is dependent on direct cell-cell contact and that this intercellular contact is mediated through interaction of CD200 expressed by MSCs and CD200R1 expressed by MPs. Furthermore, using an injury model of sterile inflammation, we show that MSCs promote MP frequencies and suppress infiltration of inflammatory cells in the inflamed tissue. We also find that downregulation of CD200 in MSCs correlates with abrogation of their immunoregulatory function. Collectively, our study provides unequivocal evidence that MSCs inhibit differentiation of MPs in the inflammatory environment via CD200-CD200R1 interaction. Stem Cells 2017;35:1532-1541.
Subject(s)
Cell Differentiation , Inflammation/pathology , Mesenchymal Stem Cells/cytology , Myeloid Progenitor Cells/pathology , Animals , Antigens, CD/metabolism , Cell Communication , Male , Mesenchymal Stem Cells/metabolism , Mice, Inbred C57BL , PhenotypeABSTRACT
Transparency of the cornea is indispensable for optimal vision. Ocular trauma is a leading cause of corneal opacity, leading to 25 million cases of blindness annually. Recently, mesenchymal stem cells (MSCs) have gained prominence due to their inflammation-suppressing and tissue repair functions. Here, we investigate the potential of MSCs to restore corneal transparency following ocular injury. Using an in vivo mouse model of ocular injury, we report that MSCs have the capacity to restore corneal transparency by secreting high levels of hepatocyte growth factor (HGF). Interestingly, our data also show that HGF alone can restore corneal transparency, an observation that has translational implications for the development of HGF-based therapy.
