title: MSC therapy attenuates obliterative bronchiolitis after murine bone marrow transplant.
abstract: BACKGROUND
  Obliterative bronchiolitis (OB) is a significant cause of morbidity and mortality after lung transplant and hematopoietic cell transplant. Mesenchymal stromal cells (MSCs) have been shown to possess immunomodulatory properties in chronic inflammatory disease.
  
  
  OBJECTIVE
  Administration of MSCs was evaluated for the ability to ameliorate OB in mice using our established allogeneic bone marrow transplant (BMT) model.
  
  
  METHODS
  Mice were lethally conditioned and received allogeneic bone marrow without (BM) or with spleen cells (BMS), as a source of OB-causing T-cells. Cell therapy was started at 2 weeks post-transplant, or delayed to 4 weeks when mice developed airway injury, defined as increased airway resistance measured by pulmonary function test (PFT). BM-derived MSC or control cells [mouse pulmonary vein endothelial cells (PVECs) or lung fibroblasts (LFs)] were administered. Route of administration [intratracheally (IT) and IV] and frequency (every 1, 2 or 3 weeks) were compared. Mice were evaluated at 3 months post-BMT.
  
  
  RESULTS
  No ectopic tissue formation was identified in any mice. When compared to BMS mice receiving control cells or no cells, those receiving MSCs showed improved resistance, compliance and inspiratory capacity. Interim PFT analysis showed no difference in route of administration. Improvements in PFTs were found regardless of dose frequency; but once per week worked best even when administration began late. Mice given MSC also had decreased peribronchiolar inflammation, lower levels of hydroxyproline (collagen) and higher frequencies of macrophages staining for the alternatively activated macrophage (AAM) marker CD206.
  
  
  CONCLUSIONS
  These results warrant study of MSCs as a potential management option for OB in lung transplant and BMT recipients.
authors.affiliation: Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Kashif
authors.initials: K
authors.lastname: Raza
authors.affiliation: Breck High School, Edina, Minnesota, United States of America.
authors.forename: Trevor
authors.initials: T
authors.lastname: Larsen
authors.affiliation: Breck High School, Edina, Minnesota, United States of America.
authors.forename: Nath
authors.initials: N
authors.lastname: Samaratunga
authors.affiliation: Pediatric Blood and Bone Marrow Transplant Program, University of Minnesota Cancer Center, Minneapolis, Minnesota, United States of America.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Price
authors.affiliation: Pediatric Blood and Bone Marrow Transplant Program, University of Minnesota Cancer Center, Minneapolis, Minnesota, United States of America.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Meyer
authors.affiliation: Pediatric Blood and Bone Marrow Transplant Program, University of Minnesota Cancer Center, Minneapolis, Minnesota, United States of America.
authors.forename: Amy
authors.initials: A
authors.lastname: Matson
authors.affiliation: Pediatric Blood and Bone Marrow Transplant Program, University of Minnesota Cancer Center, Minneapolis, Minnesota, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ehrhardt
authors.affiliation: Pediatric Blood and Bone Marrow Transplant Program, University of Minnesota Cancer Center, Minneapolis, Minnesota, United States of America.
authors.forename: Samuel
authors.initials: S
authors.lastname: Fogas
authors.affiliation: Pediatric Blood and Bone Marrow Transplant Program, University of Minnesota Cancer Center, Minneapolis, Minnesota, United States of America.
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.affiliation: Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Marshall I
authors.initials: MI
authors.lastname: Hertz
authors.affiliation: Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America; Pediatric Blood and Bone Marrow Transplant Program, University of Minnesota Cancer Center, Minneapolis, Minnesota, United States of America.
authors.forename: Angela
authors.initials: A
authors.lastname: Panoskaltsis-Mortari
mesh_terms: D000818:Animals; D001989:Bronchiolitis Obliterans / Q000628:therapy*; D005260:Female; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D019172:Transplantation Conditioning