Introduction: 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. Study design: 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-αβTCR 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.
|Original language||English (US)|
|Number of pages||8|
|Journal||American Journal of Otolaryngology - Head and Neck Medicine and Surgery|
|State||Published - Jul 2008|
Bibliographical noteFunding Information:
This work was supported in part by a research grant from the Triological Society. In addition, support was in part received from an internal Research Protocol Committee grant from The Cleveland Clinic Foundation. This study was performed in accordance with the PHS Policy on Human Case and Use of Laboratory Animals, the NIH guide for the Care and Use of Laboratory Animals, and Animal Welfare Act (7 U.S.C et seq.). The animal protocol was approved by the Institutional Animal Care and Use Committee of The Cleveland Clinic Foundation.
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