title: Comparison of the anti-inflammatory effects of induced pluripotent stem cell-derived and bone marrow-derived mesenchymal stromal cells in a murine model of corneal injury.
abstract: Mesenchymal stromal cells (MSCs) offer tremendous potential for therapeutic applications for inflammatory diseases. However, tissue-derived MSCs, such as bone marrow-derived MSCs (BM-MSCs), have considerable donor variations and limited expandability. It was recently demonstrated that MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have less pro-tumor potential and greater expandability of homogenous cell population. In this study, we investigated the anti-inflammatory effects and mechanism of iPSC-MSCs in a murine model of chemical and mechanical injury to the cornea and compared the effects with those of BM-MSCs.
  
  
  
  To create an injury, ethanol was applied to the corneal surface in mice, and the corneal epithelium was removed with a blade. Immediately after injury, mice received an intravenous injection of (i) iPSC-MSCs, (ii) BM-MSCs or (iii) vehicle. Clinical, histological and molecular assays were performed in the cornea to evaluate inflammation.
  
  
  
  We found that corneal opacity was significantly reduced by iPSC-MSCs or BM-MSCs. Histological examination revealed that the swelling and inflammatory infiltration in the cornea were markedly decreased in mice treated with iPSC-MSCs or BM-MSCs. Corneal levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were lower in iPSC-MSC- and BM-MSC-treated mice, compared with vehicle-treated controls. In contrast, iPSC-MSCs with a knockdown of the TNF-α stimulating gene (TSG)-6 did not suppress the levels of inflammatory cytokines and failed to reduce corneal opacity.
  
  
  
  Together these data demonstrate that iPSC-MSCs exert therapeutic effects in the cornea by reducing inflammation in part through the expression of TSG-6, and the effects are similar to those seen with BM-MSCs.
authors.affiliation: College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Young In
authors.initials: YI
authors.lastname: Yun
authors.affiliation: Laboratory of Ocular Regenerative Medicine and Immunology, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Se Yeon
authors.initials: SY
authors.lastname: Park
authors.affiliation: Laboratory of Ocular Regenerative Medicine and Immunology, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Laboratory of Ocular Regenerative Medicine and Immunology, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Ko
authors.affiliation: Laboratory of Ocular Regenerative Medicine and Immunology, Seoul National University Hospital, Seoul, Republic of Korea; Department of Ophthalmology, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Mee Kum
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Laboratory of Ocular Regenerative Medicine and Immunology, Seoul National University Hospital, Seoul, Republic of Korea; Department of Ophthalmology, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Won Ryang
authors.initials: WR
authors.lastname: Wee
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, Texas, USA.
authors.forename: Roxanne L
authors.initials: RL
authors.lastname: Reger
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, Texas, USA.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Gregory
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, Texas, USA.
authors.forename: Hosoon
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Surgery, Ophthalmology Section, Central Texas Veterans Health Care System, Temple, Texas, USA.
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Fulcher
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, Texas, USA.
authors.forename: Darwin J
authors.initials: DJ
authors.lastname: Prockop
authors.affiliation: Laboratory of Ocular Regenerative Medicine and Immunology, Seoul National University Hospital, Seoul, Republic of Korea; Department of Ophthalmology, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: jooyounoh77@gmail.com.
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Oh
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D065306:Corneal Injuries / Q000378:metabolism / Q000628:therapy*; D003318:Corneal Opacity / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000637:transplantation; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007634:Keratitis / Q000473:pathology / Q000628:therapy; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; C513057:Tnfaip6 protein, mouse; D014409:Tumor Necrosis Factor-alpha
keywords: bone marrow; cornea; induced pluripotent stem cell; inflammation; mesenchymal stromal cells