title: Safety and immunomodulatory effects of allogeneic canine adipose-derived mesenchymal stromal cells transplanted into the region of the lacrimal gland, the gland of the third eyelid and the knee joint.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSCs) have been extensively studied as a cellular therapeutic for various pathologic conditions. However, there remains a paucity of data regarding regional and systemic safety of MSC transplantations, particularly with multiple deliveries of allogeneic cells. The purpose of this study was to investigate the safety and systemic immunomodulatory effects of repeated local delivery of allogeneic MSCs into the region of the lacrimal gland, the gland of the third eyelid and the knee joint in dogs.
  
  
  METHODS
  Allogeneic adipose tissue-derived canine MSCs were delivered to the regions of the lacrimal gland and the third eyelid gland as well as in the knee joints of six healthy laboratory beagles as follows: six times with 1-week intervals for delivery to the lacrimal gland and the third eyelid gland regions and three to four times with 1- to 2-week intervals for intra-articular transplantations. Dogs were sequentially evaluated by clinical examination. At the conclusion of the study, dogs were humanely euthanized, and a complete gross and histopathologic examination of all organ systems was performed. Mixed leukocyte reactions were also performed before the first transplantation and after the final transplantation.
  
  
  RESULTS
  Clinical and pathologic examinations found no severe consequences after repeated MSC transplantations. Results of mixed leukocyte reactions demonstrated suppression of T-cell proliferation after MSC transplantations.
  
  
  CONCLUSIONS
  This is the first study to demonstrate regional and systemic safety and systemic immunomodulatory effects of repeated local delivery of allogeneic MSCs in vivo.
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California, USA.
authors.forename: Shin Ae
authors.initials: SA
authors.lastname: Park
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Reilly
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Wood
authors.forename: Dai Jung
authors.initials: DJ
authors.lastname: Chung
authors.forename: Danielle D
authors.initials: DD
authors.lastname: Carrade
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Deremer
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Seraphin
authors.forename: Kaitlin C
authors.initials: KC
authors.lastname: Clark
authors.forename: Allison L
authors.initials: AL
authors.lastname: Zwingenberger
authors.forename: Dori L
authors.initials: DL
authors.lastname: Borjesson
authors.forename: Kei
authors.initials: K
authors.lastname: Hayashi
authors.forename: Paul
authors.initials: P
authors.lastname: Russell
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Murphy
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D049109:Cell Proliferation; D004285:Dogs; D006801:Humans; D007719:Knee Joint / Q000473:pathology; D007765:Lacrimal Apparatus / Q000473:pathology / Q000637:transplantation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009541:Nictitating Membrane / Q000473:pathology / Q000637:transplantation
keywords: KCS; arthritis; dry eye; engraftment; immunomodulation; immunosuppression; keratoconjunctivitis sicca; osteoarthritis; stifle joint; toxicity