Modification with Methoxy Polyethylene Glycol to Grafts Alleviates Acute Graft Versus Host Disease Severity in Mice Following Haploidentical Bone Marrow Transplantation

BACKGROUND: Methoxy polyethylene glycol (mPEG) is a kind of amphoteric compound with no immunogenicity that has been used to modify various proteins covalently and to prepare versatile blood types. If mPEG modification blocks the activation of T cells in grafts, graft versus host disease (GVHD) reaction probably becomes less serious and transplantation may become successful. OBJECTIVE: To construct haploidentical bone marrow transplantation murine model and to observe the effects of mPEG modification to grafts on acute GVHD following haploidentical bone marrow transplantation. DESIGN, TIME AND SETTING: A randomized paired design experiment was performed at the Laboratory Animal Center and Pediatric Laboratory of the General Hospital of Chinese PLA between March and November 2003. MATERIALS: Twenty 8-10 week old male BALB/cH-2d mice served as donors and sixty 8-10 week old female CB6 F1 H-2d/b mice served as recipients. mPEG was provided by Sigma, USA. METHODS: Mixture of donor bone marrow and spleen cells was routinely prepared. After irradiated with 60Co γ ray at a total dose of 8.0 Gy, recipient mice were randomly divided into 3 groups, with 20 rats per group: irradiation control, non-modification, and mPEG modification. Within 12 hours after irradiation, the irradiation control group was injected with 0.5 mL RPMI-1640 culture medium via caudal vein, the non-modification group was administered with 0.5 mL non-modified mixture of bone marrow and spleen cells via caudal vein, and mice from the group were given 0.5 mL mPEG-modified mixture of bone marrow and spleen cells via caudal vein. MAIN OUTCOME MEASURES: After transplantation, hematopoietic recovery, survival rate, acute GVHD and chromosomal karyotype were studied and compared with controls. RESULTS: All mice from the irradiation control groups died within 2 weeks. The 30-day survival rate was significantly higher in the mPEG modification group than in the non-modification group (75% vs.40%, χ^2 = 5.01, P = 0.025). Histopathological examinations of skin, liver and intestine showed typical signs of acute GVHD. The mPEG modification group exhibited less severe pathological presentation and lower Thomas grading than the non-modification group. Cheimerism examination revealed complete donor-type implantation in living recipient mice at 75 days after transplantation. CONCLUSION: mPEG modification to grafts can greatly alleviate acute GVHD and enhance the survival rate of mice after haploidentical bone marrow transplantation.