GVHD after chemotherapy conditioning in allogeneic transplanted mice.
GVHD is a major complication in allogeneic SCT. Available GVHD models are mainly based on radiotherapy-conditioning and/or immune deficient mice. GVHD models based on chemotherapy-based regimens remain poorly studied, despite 50% of all transplantations being chemotherapy based. Our aim was to develop a GVHD model using chemotherapy as conditioning. Female BALB/c (H-2Kd) were conditioned with BU-CY and transplanted with 2 x 10(7) BM and 3 x 10(7) spleen cells from either C57BL/6 (H-2 Kb) mice (allogeneic setting) or from male BALB/c to serve as a control group for regimen-related toxicity and engraftment. GVHD manifestations and histopathological changes were evaluated. Chimerism and donor T cells presence in skin, intestine and liver were studied using FACS-, FISH analysis and immunohistochemistry. Allogeneic transplanted mice developed lethal GVHD starting from day+7 with both histological and clinical signs. Donor T cells accumulated in recipient skin and intestine with GVHD progression. BM-failure, apoptosis and T-lymphocyte infiltration into target organs were significantly higher in allogeneic when compared with the syngeneic group. No toxicity or GVHD signs were observed in the syngeneic setting. We report a mouse model of GVHD using BU-CY conditioning that represents the most common myeloablative-conditioning regimen in clinical SCT. This model can be utilized to study the role of conditioning on mechanisms underlying GVHD.
Sadeghi
B
B
Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Aghdami
N
N
Hassan
Z
Z
Forouzanfar
M
M
Rozell
B
B
Abedi-Valugerdi
M
M
Hassan
M
M
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002066:Busulfan / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology* / Q000503:physiopathology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D008297:Male; D051379:Mice; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods*; D014184:Transplantation, Homologous / Q000009:adverse effects
D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D002066:Busulfan