title: Safety of treatment with DLA-identical or unrelated mesenchymal stromal cells in DLA-identical canine bone marrow transplantation.
abstract: BACKGROUND
  Although in vitro and in vivo experiments have suggested that mesenchymal stromal cells (MSC) may have important immunomodulatory functions in allogeneic hematopoietic cell transplantation (HCT), results from clinical studies have been inconsistent. In the current study we investigate the safety of dog leukocyte antigen (DLA) identical or third party unrelated MSC in DLA-identical HCT.
  
  
  RESULTS
  There were no differences between treatment groups in depth of granulocyte or platelet nadirs, time to granulocyte or platelet engraftment, rate of acute GVHD or rejection. All dogs tolerated the MSC infusion well, although 2 dogs treated with unrelated MSC were euthanized on day 9 due to complications unrelated to the MSC infusion. While no formation of ectopic tissue was observed, GFP positive signals in bone marrow, spleen or liver were detected at time of necropsy in 75% and 50% of dogs treated with DLA-identical or unrelated MSC, respectively.
  
  
  CONCLUSIONS
  Treatment with DLA-identical or unrelated MSC in high dose DLA-identical HCT is safe, and provides a large animal HCT model in which to investigate immunological mechanisms and optimal treatment strategies for future human trials.
  
  
  METHODS
  Fourteen dogs were treated with 920 cGy total body irradiation (TBI) followed by transplantation of marrow from DLA-identical littermates and immunosuppression with cyclosporine. Prior to infusion of marrow, dogs received infusions of DLA-identical MSC from the marrow donor (n = 4), unrelated MSC (n = 4), or culture medium (n = 6), within 1 h of TBI. MSC obtained from relevant donors were ex-vivo expanded and transduced with GFP-retrovirus before infusion.
authors.affiliation: Clinical Research Division; Fred Hutchinson Cancer Research Center; Seattle, WA USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Kornblit
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Leisenring
authors.forename: Erlinda B
authors.initials: EB
authors.lastname: Santos
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000627:therapeutic use; D004285:Dogs; D006084:Graft Rejection / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008099:Liver / Q000166:cytology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D023421:Models, Animal; D013154:Spleen / Q000166:cytology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors
chemical_list: D006649:Histocompatibility Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine
keywords: allogeneic hematopoietic cell transplantation; canine transplantation model; green fluorescent protein transduced; mesenchymal stem cells; third party