OBJECTIVE: Stable mixed hematopoietic chimerism can be established in a canine stem cell transplantation model using a conditioning consisting of total body irradiation (TBI; 2 Gy) and postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporin (CSA). Reduction of TBI had resulted previously in graft rejection in this model. We investigated whether postgrafting stimulation of donor T cells against recipient's hematopoietic antigens or graft augmentation with donor monocyte-derived dendritic cells (MoDC) promote engraftment following 1 Gy TBI. MATERIALS AND METHODS: All dogs received dog leukocyte-antigen-identical bone marrow transplantation. Dogs were conditioned with either 2 Gy TBI (group 1) or 1 Gy TBI, followed by repetitive recipient hematopoietic cell lysate vaccinations (group 2) or graft augmentation with MoDC (group 3). Immunosuppression consisted of CSA and MMF. RESULTS: In group 1, four animals remained stable chimeras for >110 weeks, and three rejected their grafts (week 10, week 14, week 16). All dogs in groups 2 and 3 rejected their graft (median: week 10 and 11, respectively). Peak chimerism and engraftment duration was shorter in the 1-Gy groups (p < 0.05) compared to group 1. CONCLUSION: Neither postgrafting vaccination nor graft augmentation with MoDC were effective in supporting durable engraftment. Additional modifications are necessary to improve potential strategies aimed at establishment of early tissue specific graft-vs-host reactions.
OBJECTIVE: Stable mixed hematopoietic chimerism can be established in a canine stem cell transplantation model using a conditioning consisting of total body irradiation (TBI; 2 Gy) and postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporin (CSA). Reduction of TBI had resulted previously in graft rejection in this model. We investigated whether postgrafting stimulation of donor T cells against recipient's hematopoietic antigens or graft augmentation with donor monocyte-derived dendritic cells (MoDC) promote engraftment following 1 Gy TBI. MATERIALS AND METHODS: All dogs received dog leukocyte-antigen-identical bone marrow transplantation. Dogs were conditioned with either 2 Gy TBI (group 1) or 1 Gy TBI, followed by repetitive recipient hematopoietic cell lysate vaccinations (group 2) or graft augmentation with MoDC (group 3). Immunosuppression consisted of CSA and MMF. RESULTS: In group 1, four animals remained stable chimeras for >110 weeks, and three rejected their grafts (week 10, week 14, week 16). All dogs in groups 2 and 3 rejected their graft (median: week 10 and 11, respectively). Peak chimerism and engraftment duration was shorter in the 1-Gy groups (p < 0.05) compared to group 1. CONCLUSION: Neither postgrafting vaccination nor graft augmentation with MoDC were effective in supporting durable engraftment. Additional modifications are necessary to improve potential strategies aimed at establishment of early tissue specific graft-vs-host reactions.
Authors: H Jonuleit; A Giesecke-Tuettenberg; T Tüting; B Thurner-Schuler; T B Stuge; L Paragnik; A Kandemir; P P Lee; G Schuler; J Knop; A H Enk Journal: Int J Cancer Date: 2001-07-15 Impact factor: 7.396
Authors: T R Spitzer; S McAfee; R Sackstein; C Colby; H C Toh; P Multani; S Saidman; D W Weyouth; F Preffer; C Poliquin; A Foley; B Cox; D Andrews; D H Sachs; M Sykes Journal: Biol Blood Marrow Transplant Date: 2000 Impact factor: 5.742
Authors: R Childs; E Clave; N Contentin; D Jayasekera; N Hensel; S Leitman; E J Read; C Carter; E Bahceci; N S Young; A J Barrett Journal: Blood Date: 1999-11-01 Impact factor: 22.113
Authors: P A McSweeney; D Niederwieser; J A Shizuru; B M Sandmaier; A J Molina; D G Maloney; T R Chauncey; T A Gooley; U Hegenbart; R A Nash; J Radich; J L Wagner; S Minor; F R Appelbaum; W I Bensinger; E Bryant; M E Flowers; G E Georges; F C Grumet; H P Kiem; B Torok-Storb; C Yu; K G Blume; R F Storb Journal: Blood Date: 2001-06-01 Impact factor: 22.113
Authors: E K Waller; H Rosenthal; T W Jones; J Peel; S Lonial; A Langston; I Redei; I Jurickova; M W Boyer Journal: Blood Date: 2001-05-15 Impact factor: 22.113
Authors: J M Zaucha; E Zellmer; G Georges; M T Little; R Storb; B Storer; B Torok-Storb Journal: Biol Blood Marrow Transplant Date: 2001 Impact factor: 5.742