title: Allogeneic Compact Bone-Derived Mesenchymal Stem Cell Transplantation Attenuates the Severity of Idiopathic Pneumonia Syndrome in a Murine Bone Marrow Transplantation Model.
abstract: OBJECTIVE
  Idiopathic pneumonia syndrome (IPS) is a serious and life-threatening lung complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and currently no effective therapies exist. This study was designed to determine whether transplantation of allogeneic murine compact bone derived- mesenchymal stem cells (CB-MSCs) could prevent the development of IPS.
  
  
  METHODS
  We tested the effects of CB-MSCs transplantation on IPS using an established murine model of C57BL/6 (H-2b)→BALB/c (H-2d). Survival rates, body weight change, clinical GVHD scores, lung histological changes were assessed after IPS induction. Mechanistically, concentrations of cytokines (TNF-α, IFN-γ and IL-4) and chemokines (CCL5, CXCL9 and CXCL10) in bronchoalveolar lavage fluid (BALF) from the recipient mice were measured at different time point post-transplantation. CD4+CD25+Foxp3+ regulatory T cell (Treg) percentage, CCR5, CXCR3 and CCR7 expression on CD3+ T cells, and lung CXCR3, CCR5, CCR7, T-bet and GATA-3 mRNA levels were also evaluated at different time point post-transplantation.
  
  
  RESULTS
  Co-transplantation of CB-MSCs significantly attenuated the severity of lung injuries and increased survival rate of mice compared to non-cotransplanted mice. A higher Treg percentage, reduction of TNF-α, IFN-γ, CCL5, CXCL9 and CXCL10 levels, down-regulation of CXCR3 and CCR5, as well as up-regulation of CCR7, were observed in MSCs co-transplantation mice. Also, the prophylactic effect of CB-MSCs was associated with a shift of Th1/Th2 balance toward anti-inflammatory Th2 polarization.
  
  
  CONCLUSIONS
  Allogeneic CB-MSCs effectively controlled the occurrence of IPS due to its profound immunomodulatory capacity. This may offer a novel prophylactic approach for IPS after allo-HSCT.
authors.affiliation: Department of Hematology, Peking University First Hospital, Beijing, China.
authors.forename: Shu-Kai
authors.initials: SK
authors.lastname: Qiao
authors.forename: Han-Yun
authors.initials: HY
authors.lastname: Ren
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Shi
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D001992:Bronchoalveolar Lavage Fluid; D016764:Cell Polarity; D018925:Chemokines / Q000378:metabolism; D000071538:Cortical Bone / Q000166:cytology*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D055370:Lung Injury / Q000150:complications / Q000473:pathology / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014184:Transplantation, Homologous; D014867:Water / Q000378:metabolism; D015431:Weight Loss
chemical_list: D018925:Chemokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D014867:Water