GVHD after chemotherapy conditioning in allogeneic transplanted mice

• Published in: Bone marrow transplantation (Basingstoke) Vol. 42; no. 12; pp. 807 - 818
• Main Authors: SADEGHI, B, AGHDAMI, N, HASSAN, Z, FOROUZANFAR, M, ROZELL, B, ABEDI-VALUGERDI, M, HASSAN, M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.12.2008
• Subjects: acute myeloid-leukemia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animal models; Animals; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Apoptosis; Biological and medical sciences; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; bone-marrow-transplantation; Busulfan - administration & dosage; Chemotherapy; chemotherapy conditioning; Chimerism; Complications and side effects; Conditioning; Cyclophosphamide - administration & dosage; Disease Models, Animal; Dose-Response Relationship, Drug; Drug therapy; Female; Flow cytometry; Graft versus host reaction; Graft vs Host Disease - etiology; Graft vs Host Disease - physiopathology; GVHD; hematopoietic stem cell transplantation; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic stem cells; Histocompatibility antigen H-2; Immune response; Immunohistochemistry; in-vivo; Intestine; lethal graft; Lymphocytes; Lymphocytes T; Male; Medical sciences; Medicin och hälsovetenskap; Mice; minor histocompatibility antigens; mouse model; NATURAL SCIENCES; NATURVETENSKAP; Organs; Radiation therapy; randomized-trial; Regulation; Risk factors; Skin; Spleen; Stem cell transplantation; Syngeneic grafts; t-cells; total-body irradiation; Toxicity; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation Conditioning - adverse effects; Transplantation Conditioning - methods; Transplantation, Homologous - adverse effects; versus-host-disease; Sweden; Antineoplastic agent; Stem cell; Hematopoietic cell; Homograft; GVHD; BU; hematopoietic stem cell transplantation; Graft; Complication; Busulfan; Conditioning; Immunopathology; Graft versus host disease; Hematology; mouse model; Rodentia; Alkanediol; chemotherapy conditioning; Alkanesulfonic acid; Alkylating agent; Vertebrata; Chemotherapy; Mammalia; Treatment; Mouse; Nitrogen mustard; Animal; CY
• ISSN: 0268-3369; 1476-5365; 1476-5365
• DOI: 10.1038/bmt.2008.261

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.