title: Umbilical cord mesenchymal stem cells suppress host rejection: the role of the glycocalyx.
abstract: Umbilical cord mesenchymal stem cells (UMSCs) have unique immunosuppressive properties enabling them to evade host rejection and making them valuable tools for cell therapy. We previously showed that human UMSCs survive xenograft transplantation and successfully correct the corneal clouding defects associated with the mouse model for the congenital metabolic disorder mucopolysaccharidosis VII. However, the precise mechanism by which UMSCs suppress the immune system remains elusive. This study aimed to determine the key components involved in the ability of the UMSCs to modulate the inflammatory system and to identify the inflammatory cells that are regulated by the UMSCs. Our results show that human UMSCs transplanted into the mouse stroma 24 h after an alkali burn suppress the severe inflammatory response and enable the recovery of corneal transparency within 2 weeks. Furthermore, we demonstrated in vitro that UMSCs inhibit the adhesion and invasion of inflammatory cells and also the polarization of M1 macrophages. UMSCs also induced the maturation of T-regulatory cells and led to inflammatory cell death. Moreover, UMSCs exposed to inflammatory cells synthesize a rich extracellular glycocalyx composed of the chondroitin sulfate-proteoglycan versican bound to a heavy chain (HC)-modified hyaluronan (HA) matrix (HC-HA). This matrix also contains TNFα-stimulated gene 6 (TSG6), the enzyme that transfers HCs to HA, and pentraxin-3, which further stabilizes the matrix. Our results, both in vivo and in vitro, show that this glycocalyx confers the ability for UMSCs to survive the host immune system and to regulate the inflammatory cells.
authors.affiliation: From the Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio 45267-0838, vcoulsonthomas@gmail.com.
authors.forename: Vivien Jane
authors.initials: VJ
authors.lastname: Coulson-Thomas
authors.affiliation: From the Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio 45267-0838, the Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio 45229, and.
authors.forename: Tarsis Ferreira
authors.initials: TF
authors.lastname: Gesteira
authors.affiliation: the Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio 44195.
authors.forename: Vincent
authors.initials: V
authors.lastname: Hascall
authors.affiliation: From the Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio 45267-0838.
authors.forename: Winston
authors.initials: W
authors.lastname: Kao
mesh_terms: D000818:Animals; D001483:Base Sequence; D016039:Corneal Transplantation; D017931:DNA Primers; D019276:Glycocalyx / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D033581:Stem Cell Transplantation; D014470:Umbilical Cord / Q000166:cytology* / Q000276:immunology
chemical_list: D017931:DNA Primers
keywords: Chondroitin Sulfate; Glycosaminoglycan; Hyaluronate; Inflammation; Mesenchymal Stem Cells (MSCs); Versican