5.1 Experimental animal pretreatment
Before ALL cell transplantation, the experimental animals should be pretreated to produce bone marrow suppression and immunosuppression, thereby reducing or eliminating the immune rejection reaction of immune cells to human cell implantation and improving the success rate of transplantation. The common pretreatment modalities nowadays mainly include γ-ray total body irradiation (TBI), injection of cytotoxic drugs and administration of natural killer cell monoclonal antibodies to experimental animals. TBI can significantly improve the success rate of transplantation, the success rate of transplantation with TBI was 91.7%, while without TBI it was only 15.4%(Patel et al., 2014). However, mice treated with high-dose TBI have high mortality, while low-dose TBI resulted in low cell implantation rate. Therefore, injection of cytotoxic drugs is more common. The study found that when NSG mice were given a TBI dose of 2.4Gy, the survival rate at week 24 was only 33%, while the survival rate of NSG mice that received a large dose of busulfan was 100% at week 24(Choi et al., 2011).Anti-CD122 antibody pretreatment is also commonly used, which can inhibit the activity of natural killer(NK) cells and target NK cells and macrophages, thereby exerting an immunosuppressive effect(Yuan, Dong, Tsurushita, Tso & Fu, 2018).
Transplantation donors generally choose immune-deficient mice aged 4-5 weeks and the main methods of transplantation are subcutaneous injection, tail vein injection and intraperitoneal injection. The number of cell inoculation is generally 106-107 per mouse. Mice generally show symptoms of slowness, paralysis, and curvature of the spine in about three weeks, and leukemic cell infiltration can be detected in peripheral blood, bone marrow, liver, spleen, lung and meninges.
5.2 Humanized Mouse Models