title: Treatment for salivary gland hypofunction at both initial and advanced stages of Sjögren-like disease: a comparative study of bone marrow therapy versus spleen cell therapy with a 1-year monitoring period.
abstract: OBJECTIVE
  Non-obese diabetic mice (NOD) exhibit autoimmune Sjögren-like disease (SS-like). We reported previously that a combined-therapy consisting of immuno- and cell-based therapy rescued NOD from SS-like. However, therapies tested to date on NOD mice were aimed at the initial phase of SS-like. It is unknown whether therapies are effective in restoring salivary function when given at an advanced phase of SS-like.
  
  
  METHODS
  The efficacy of two therapies (bone marrow versus spleen cells) was compared head-to-head for halting/reversing salivary hypofunction at two critical time points of SS-like (7-week-old NOD with normal saliva output and 20-week-old NOD with minimal saliva). NOD mice were divided into four groups: (i) control, (ii) complete Freund's adjuvant (CFA), (iii) bone marrow transplants with CFA or (iv) spleen cell transplants with CFA. Mice were monitored 8-12 months after therapy.
  
  
  RESULTS
  Both cell therapies were effective during the initial phase of SS-like; salivary flow rates were maintained between 80-100% of pre-symptomatic levels. Spleen cell therapy was better than bone marrow when administered in the initial phase of SS-like. When cell therapies were given at an advanced phase of SS-like (20 weeks and older), salivary flow rates improved but were at best 50% of pre-symptomatic levels. Both cell therapies decreased tumor necrosis factor-α, transforming growth factor-β1 levels and T and B cells while increasing epidermal growth factor and regulatory T cells. Elevated serum epidermal growth factor levels were measured in spleen-treated mice.
  
  
  CONCLUSIONS
  A therapeutic effect in advanced phase disease, albeit in mice, holds promise for humans in which Sjögren syndrome is generally not diagnosed until a late stage.
authors.affiliation: McGill University, Faculty of Dentistry, Craniofacial Tissue Engineering, and Stem Cells Laboratory, Montreal, Quebec, Canada; University of Toronto, Molecular Genetics Department, Toronto, Ontario, Canada.
authors.forename: Saeed
authors.initials: S
authors.lastname: Khalili
authors.affiliation: Harvard Medical School, Faculty of Medicine, Boston, Massachusetts, USA.
authors.forename: Denise L
authors.initials: DL
authors.lastname: Faustman
authors.affiliation: McGill University, Faculty of Dentistry, Craniofacial Tissue Engineering, and Stem Cells Laboratory, Montreal, Quebec, Canada.
authors.forename: Younan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: McGill University, Faculty of Dentistry, Craniofacial Tissue Engineering, and Stem Cells Laboratory, Montreal, Quebec, Canada; Nagasaki University Graduate School of Biomedical Science, Department of Regenerative Oral Surgery, Nagasaki, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sumita
authors.affiliation: McGill University, Faculty of Medicine, Montreal, Quebec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Blank
authors.affiliation: McGill University, Faculty of Medicine, Montreal, Quebec, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Peterson
authors.affiliation: Fukuoka University, Faculty of Medicine, Fukuoka, Japan. Electronic address: skodama@fukuoka-u.ac.jp.
authors.forename: Shohta
authors.initials: S
authors.lastname: Kodama
authors.affiliation: McGill University, Faculty of Dentistry, Craniofacial Tissue Engineering, and Stem Cells Laboratory, Montreal, Quebec, Canada. Electronic address: simon.tran@mcgill.ca.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Tran
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D012466:Salivary Gland Diseases / Q000150:complications / Q000628:therapy*; D012859:Sjogren's Syndrome / Q000150:complications / Q000628:therapy*; D013154:Spleen / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: Sjögren syndrome; autoimmune disease; cell therapy; immunotherapy; salivary gland; xerostomia