[Effect of chemical modification of grafts on the survival improvement post haploidentical bone marrow transplantation in mice].
OBJECTIVE
Human leukocyte antigen (HLA) haploidentical bone marrow is a potential source of donor to children for its availability. The drawback is deleterious graft versus host disease (GVHD) reaction post transplantation because of the incompatibility of HLA antigen expression between donors and recipients, in which donor T lymphocyte is stimulated to proliferate and differentiate. The methoxy polyethylene glycol (mPEG) is a kind of amphoteric compound without immunogenicity, which was used to modify various proteins covalently and to prepare the versatile blood type. If mPEG modification blocks the activation of T cells in grafts, GVHD reaction probably would become less serious and transplantation might become successful. The aim of this study was to verify the improvement of haploidentical bone marrow transplantation (BMT) in a murine model by using mPEG of certain concentration to modify the grafts.


METHODS
Male BALB/c mice were chosen as the donor, and female CB(6)F(1) mice as the recipient. There were three groups of mPEG modification, non-modification and irradiation control, and 20 mice in each group. The modified and non-modified mixture of bone marrow and spleen cells (as T lymphocytes) were transplanted to haploidentical lethally irradiated CB(6)F(1) mice via the tail vein. After the transplant, the hematopoietic recovery, survival rate, acute graft versus host disease (aGVHD) and chromosomal karyotype were analyzed and compared with controls.


RESULTS
Seventy-five percent (15/20) of mice survived in the group of mPEG modification, while only 40% (8/20) survived in the group without the modification (chi(2) = 5.01, P = 0.025). And 100% mice died in the group of the irradiation control within 2 weeks. The hematopoietic recovery in the group of mPEG modification was show n to be faster than that in the group without modification (P < 0.05). Histopathological examination of the skin, liver and intestine showed typical signs of aGVHD, but the GVHD grading in the group of modification was less severe. The recipient mice in both groups of transplantation surviving for more than 75 days showed complete donor-type implantation by the chimerism examination.


CONCLUSIONS
The modification of grafts by mPEG could alleviate aGVHD and improve the survival rate of mice after the haploidentical bone marrow transplantation.
Yang
Guang
G
Department of Pediatrics, the General Hospital of PLA, Beijing 100853, China.
Tang
Suo-qin
SQ
Zhang
Xiao-fei
XF
Liu
Li-zhen
LZ
Huang
Dong-sheng
DS
Wang
Jian-wen
JW
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D004195:Disease Models, Animal; D006085:Graft Survival / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D006680:HLA Antigens; D007166:Immunosuppressive Agents; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol