title: Role of Human Corneal Stroma-Derived Mesenchymal-Like Stem Cells in Corneal Immunity and Wound Healing.
abstract: Corneal tissue regeneration is of crucial importance for maintaining normal vision. We aimed to isolate and cultivate human corneal stroma-derived mesenchymal stem-like cells (CSMSCs) from the central part of cadaver corneas and study their phenotype, multipotency, role in immunity and wound healing. The isolated cells grew as monolayers in vitro, expressed mesenchymal- and stemness-related surface markers (CD73, CD90, CD105, CD140b), and were negative for hematopoietic markers as determined by flow cytometry. CSMSCs were able to differentiate in vitro into fat, bone and cartilage. Their gene expression profile was closer to bone marrow-derived MSCs (BMMSCs) than to limbal epithelial stem cells (LESC) as determined by high-throughput screening. The immunosuppressive properties of CSMSCs were confirmed by a mixed lymphocyte reaction (MLR), while they could inhibit proliferation of activated immune cells. Treatment of CSMSCs by pro-inflammatory cytokines and toll-like receptor ligands significantly increased the secreted interleukin-6 (IL-6), interleukin-8 (IL-8) and C-X-C motif chemokine 10 (CXCL-10) levels, as well as the cell surface adhesion molecules. CSMSCs were capable of closing a wound in vitro under different stimuli. These cells thus contribute to corneal tissue homeostasis and play an immunomodulatory and regenerative role with possible implications in future cell therapies for treating sight-threatening corneal diseases.
authors.affiliation: Stem Cells and Eye Research Laboratory, Department of Ophthalmology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Veréb
authors.affiliation: Center for Clinical Genomics and Personalized Medicine, Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary.
authors.forename: Szilárd
authors.initials: S
authors.lastname: Póliska
authors.affiliation: Stem Cells and Eye Research Laboratory, Department of Ophthalmology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Réka
authors.initials: R
authors.lastname: Albert
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Ole Kristoffer
authors.initials: OK
authors.lastname: Olstad
authors.affiliation: Department of Medical Chemistry, University of Debrecen, Debrecen, Hungary.
authors.forename: Anita
authors.initials: A
authors.lastname: Boratkó
authors.affiliation: Department of Medical Chemistry, University of Debrecen, Debrecen, Hungary.
authors.forename: Csilla
authors.initials: C
authors.lastname: Csortos
authors.affiliation: Centre of Eye Research, Department of Ophthalmology, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Morten C
authors.initials: MC
authors.lastname: Moe
authors.affiliation: Stem Cells and Eye Research Laboratory, Department of Ophthalmology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Facskó
authors.affiliation: Stem Cells and Eye Research Laboratory, Department of Ophthalmology, Faculty of Medicine, University of Szeged, Szeged, Hungary.|Centre of Eye Research, Department of Ophthalmology, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Goran
authors.initials: G
authors.lastname: Petrovski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation; D002478:Cells, Cultured; D003315:Cornea / Q000276:immunology* / Q000502:physiology*; D003319:Corneal Stroma / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D057166:High-Throughput Screening Assays; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000502:physiology*; D008875:Middle Aged; D008954:Models, Biological; D012038:Regeneration; D014945:Wound Healing
chemical_list: D000954:Antigens, Surface; D016207:Cytokines