title: Donor bone marrow in laryngeal transplantation: results of a rat study.
abstract: BACKGROUND
  The concept of donor bone marrow transplantation has been successfully used in human solid organ transplantation to increase recipient chimerism. The development of recipient chimerism is associated with a decreased need for immunosuppression and even donor-specific tolerance. In this study, we attempted to augment recipient chimerism by the transfer of donor bone marrow at the time of rat laryngeal transplant.
  
  
  METHODS
  Experimental study in rats.
  
  
  METHODS
  The study used a well-established semiallogeneic rat laryngeal transplant model with partial major histocompatibility complex (MHC)-mismatched Lewis-Brown-Norway donors and Lewis recipients. Donor bone marrow was introduced at transplantation via (1) intravascular injection and (2) transfer of a vascularized femoral bone graft. Recipients were treated with an established immunosuppressive regimen consisting of everolimus and anti-alphabetaTCR monoclonal antibody for a 7-day perioperative course. Animals received a 5-day boost of the same regimen at 90 days posttransplantation. Parathyroid hormone levels and histological examination were used for rejection surveillance and scoring.
  
  
  RESULTS
  Animals treated with intravenous bone marrow injection followed by perioperative and pulsed immunosuppression commonly demonstrated early rejection (90%). Animals receiving transfer of vascularized donor femur had an average rejection score of 2.9 (scale, 1-6) at 180 days posttransplantation. Mixed-lymphocyte reaction did not demonstrate donor-specific tolerance in the latter group, and chimerism was less than 1%.
  
  
  CONCLUSIONS
  In the rat laryngeal transplant model, donor bone marrow does not consistently lead to augmentation of peripheral chimerism using our established pulsed immunosuppression protocol. In many cases, rejection occurred earlier than animals not receiving bone marrow. This may be due to several different factors including (1) an element of graft-vs-host disease, (2) inability to establish bone marrow engraftment due to our short-term perioperative immunosuppression regimen, or (3) preferential rejection of donor bone marrow cells.
authors.affiliation: Head and Neck Institute, Cleveland Clinic Foundation, Cleveland, OH, USA. samirkhariwala@hotmail.com
authors.forename: Samir S
authors.initials: SS
authors.lastname: Khariwala
authors.forename: Olivia
authors.initials: O
authors.lastname: Dan
authors.forename: Robert R
authors.initials: RR
authors.lastname: Lorenz
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Klimczak
authors.forename: Maria
authors.initials: M
authors.lastname: Siemionow
authors.forename: Marshall
authors.initials: M
authors.lastname: Strome
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D005434:Flow Cytometry; D006084:Graft Rejection; D007165:Immunosuppression Therapy / Q000379:methods; D007830:Larynx / Q000473:pathology / Q000637:transplantation*; D010281:Parathyroid Hormone / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D018183:Transplantation Chimera; D016896:Treatment Outcome
chemical_list: D010281:Parathyroid Hormone