Establishment and evaluation of mouse model of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
10.16781/j.0258-879x.2016.12.1501
- Author:
Wen-Fang YI
1
Author Information
1. Department of Pediatrics, Zhuhai People’sHospital
- Publication Type:Journal Article
- Keywords:
Animal models;
Gratt vs host disease;
Hematopoietic stem cell transplantation;
Homologous transplantation
- From:
Academic Journal of Second Military Medical University
2016;37(12):1501-1505
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish a mouse model of chronic gratt-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation using chemotherapy preconditioning regimens. Methods The donor mouse was BALB/ cH-2kd and the recipients mouse was C57BL/6H-2kb. The pretreatment of recipient mouse was performed using different doses of chemotherapy drugs, busulfan (BU) 20 mg/(kg • d) ×4 d + cyclophosphamide (CTX) 150 mg/(kg • d) × 2 d, or BU 20 mg/ (kg • d) ×4 d + CTX 100 mg/(kg • d) × 2 d, and then the recipient mouse was injected with different doses of spleen cells (6×107 or 4 × 107 cells) and/or same dose of bone marrow cells (2× 107 cells) to establish the model of chronic GVHD. Hematopoietic chimerism analysis, clinical score and histopathology were used to evaluate the model. Results The high level of recipient-donor mixture chimera was established by pretreated by BU 20 mg/ (kg • d) ×4 d + CTX 150 mg/ (kg • d) × 2d and 2× 107 bone marrow mononuclear cells +6×107 spleen mononuclear cells . The onset of GVHD was concentrated at the 30-90 d after injecting spleen cells of the donor mouse. The clinical scores and incidence rate of chronic GVHD were significantly increased in the large numbers of cells and high doses of chemotherapy transplantation group compared with those in smaller numbers of cells and lower doses of chemotherapy groups (P<0.05). Pathological changes such as cellular and structural abnormalities and inflammatory cell infiltration were noted in the intestines, liver, skin and spleen of the model mice. Conclusion Bone marrow mononuclear cells (2×107 cells) + spleenmononuclear cells (6 × 107 or 4 × 107 cells) can be used to establish a stable chronic GVHD mouse modll via preconditioning with BU and CTX, which paves a way for clinical treatment of chronic GVHD.
