title: Analysis of multipotent mesenchymal stromal cells used for acute graft-versus-host disease prophylaxis.
abstract: BACKGROUND
  Multipotent mesenchymal stromal cells (MSCs) are used for prophylaxis of acute graft-versus-host disease (aGvHD) after allogeneic hematopoietic cell transplantation (allo-HCT). Not all samples of MSC are efficient for aGvHD prevention. The suitability of MSCs for aGvHD prophylaxis was studied.
  
  
  METHODS
  MSCs were derived from the bone marrow (BM) of HCT donor and cultivated for no more than three passages. The characteristics of donor BM samples including colony-forming unit fibroblast (CFU-F) concentration, growth parameters of MSCs, and the relative expression levels (REL) of different genes were analyzed. MSCs were injected intravenously precisely at the moment of blood cell reconstitution.
  
  
  RESULTS
  MSCs infusion induced a significant threefold decrease in aGvHD development and improved overall survival compared with the standard prophylaxis group. In ineffective MSC samples (9.4%), a significant decrease in total cell production and the REL of CSF1, FGFR1, and PDGFRB was observed. In all studied BM samples, the cumulative MSC production and CFU-F concentrations decreased with age. The expression levels of FGFR2, PPARG, and VEGF differed by age.
  
  
  CONCLUSIONS
  A universal single indicator for the prediction of MSC eligibility for aGvHD prophylaxis was not identified. A multiparameter mathematical model for selecting MSC samples effective for the prevention of aGvHD was proposed.
authors.affiliation: Federal Government Budget Institution National Research Center for Hematology, Ministry of Health, Moscow, Russia.
authors.forename: Larisa A
authors.initials: LA
authors.lastname: Kuzmina
authors.affiliation: Federal Government Budget Institution National Research Center for Hematology, Ministry of Health, Moscow, Russia.
authors.forename: Nataliya A
authors.initials: NA
authors.lastname: Petinati
authors.affiliation: Federal Government Budget Institution National Research Center for Hematology, Ministry of Health, Moscow, Russia.
authors.forename: Irina N
authors.initials: IN
authors.lastname: Shipounova
authors.affiliation: Federal Government Budget Institution National Research Center for Hematology, Ministry of Health, Moscow, Russia.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Sats
authors.affiliation: Federal Government Budget Institution National Research Center for Hematology, Ministry of Health, Moscow, Russia.
authors.forename: Alexey E
authors.initials: AE
authors.lastname: Bigildeev
authors.affiliation: Department of Molecular Immunology, Faculty of Biology, Moscow State University, Moscow, Russia.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Zezina
authors.affiliation: Department of Molecular Immunology, Faculty of Biology, Moscow State University, Moscow, Russia.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Popova
authors.affiliation: Federal Government Budget Institution National Research Center for Hematology, Ministry of Health, Moscow, Russia.
authors.forename: Nina J
authors.initials: NJ
authors.lastname: Drize
authors.affiliation: Federal Government Budget Institution National Research Center for Hematology, Ministry of Health, Moscow, Russia.
authors.forename: Elena N
authors.initials: EN
authors.lastname: Parovichnikova
authors.affiliation: Federal Government Budget Institution National Research Center for Hematology, Ministry of Health, Moscow, Russia.
authors.forename: Valery G
authors.initials: VG
authors.lastname: Savchenko
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D047495:PPAR gamma / Q000235:genetics / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000276:immunology; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000276:immunology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D019653:Myeloablative Agonists; D047495:PPAR gamma; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; C000605860:PDGFRB protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D016186:Receptor, Macrophage Colony-Stimulating Factor; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: acute graft-versus-host disease prophylaxis; colony-forming unit fibroblast; gene expression; mesenchymal stromal cell