title: Delivery of Bone Marrow-Derived Mesenchymal Stem Cells Improves Tear Production in a Mouse Model of Sjögren's Syndrome.
abstract: The purpose of the present study was to test the potential of mouse bone marrow-derived mesenchymal stem cells (BD-MSCs) in improving tear production in a mouse model of Sjögren's syndrome dry eye and to investigate the underlying mechanisms involved. NOD mice (n= 20) were randomized to receive i.p. injection of sterile phosphate buffered saline (PBS, control) or murine BD-MSCs (1 × 106cells). Tears production was measured at baseline and once a week after treatment using phenol red impregnated threads. Cathepsin S activity in the tears was measured at the end of treatment. After 4 weeks, animals were sacrificed and the lacrimal glands were excised and processed for histopathology, immunohistochemistry, and RNA analysis. Following BD-MSC injection, tears production increased over time when compared to both baseline and PBS injected mice. Although the number of lymphocytic foci in the lacrimal glands of treated animals did not change, the size of the foci decreased by 40.5% when compared to control animals. The mRNA level of the water channel aquaporin 5 was significantly increased following delivery of BD-MSCs. We conclude that treatment with BD-MSCs increases tear production in the NOD mouse model of Sjögren's syndrome. This is likely due to decreased inflammation and increased expression of aquaporin 5.
authors.affiliation: Department of Comprehensive Care, Tufts University School of Dental Medicine, Boston, MA, USA.
authors.forename: Hema S
authors.initials: HS
authors.lastname: Aluri
authors.affiliation: Department of Comprehensive Care, Tufts University School of Dental Medicine, Boston, MA, USA.
authors.forename: Mahta
authors.initials: M
authors.lastname: Samizadeh
authors.affiliation: Department of Ophthalmology, USC Roski Eye Institute, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Edman
authors.affiliation: Department of Comprehensive Care, Tufts University School of Dental Medicine, Boston, MA, USA.
authors.forename: Dillon R
authors.identifier: 0000-0003-0053-9842
authors.initials: DR
authors.lastname: Hawley
authors.affiliation: Department of Comprehensive Care, Tufts University School of Dental Medicine, Boston, MA, USA.
authors.forename: Helene L
authors.initials: HL
authors.lastname: Armaos
authors.affiliation: Department of Ophthalmology, USC Roski Eye Institute, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
authors.forename: Srikanth R
authors.initials: SR
authors.lastname: Janga
authors.affiliation: University of Southern California School of Pharmacy, Los Angeles, CA, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Sendra
authors.affiliation: Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, USA; Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Pedram
authors.initials: P
authors.lastname: Hamrah
authors.affiliation: Department of Comprehensive Care, Tufts University School of Dental Medicine, Boston, MA, USA.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Kublin
authors.affiliation: Department of Ophthalmology, USC Roski Eye Institute, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA; University of Southern California School of Pharmacy, Los Angeles, CA, USA.
authors.forename: Sarah F
authors.identifier: 0000-0001-8195-5703
authors.initials: SF
authors.lastname: Hamm-Alvarez
authors.affiliation: Department of Comprehensive Care, Tufts University School of Dental Medicine, Boston, MA, USA; Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Driss
authors.identifier: 0000-0003-1622-4431
authors.initials: D
authors.lastname: Zoukhri