The Effect Of Recombinant Human Bone Morphogenetic Protein-2 On The Repaire Of Hemapoietic Damage By Bone Marrow Suppression

Belonging to one member of the TGF-? superfamily,bone morphogenetic protein(BMP)is the only local growth factor with independent bone-inducing ability so far.Recently,it has been reported that BMPs are closely related to animal embryonic hematopoiesis and evidence has confirmed their important roles in embryonic occurrence and differentiation during mesoderm induction and differentiation of hematopoietic system.Experiments on BMPs repairing the adult animal hematopoietic damage are also verified.This paper aims at studying the repairing of recombinant human bone morphogenetic protein-2(rhBMP-2)on bone marrow suppression hematopoietic injury through three separate hematopoietic damage models of mice.Mice was given cyclophosphamide as chemotherapy drugs to build acute chemotherapy damage model and then cured by rhBMP-2 through abdominal cavity injection for six days.The results showed that the number of leukocytes in peripheral blood of mice treated with rhBMP-2 recovered faster than the chemotherapy control group;comparing to the chemotherapy control group of mice,the number of bone marrow mononuclear cells had been significantly improved,and the number of bone marrow mononuclear cells in mice injected with high dose rhBMP-2 was closed enough to the normal values on the eleventh day;cell percentages of CD34+ and CD45+ cells and the gene expression of CD34 and CD45 molecule in bone marrow mononuclear cells of the treated group was also increased;the spleen coefficient showed rh BMP-2 could help to restore the function of spleen after chemotherapy damage;colony culture experiment showed that rhBMP-2 therapeutic group was superior to chemotherapy control on numbers and cell morphology;cell cycle detection showed rhBMP-2 could protect G1 phase of bone marrow cells from apoptosis to maintain bone marrow cells,and protect bone marrow cells from damage by cyclophosphamide.All these results showed rhBMP-2 could promote the recovery of hematopoietic function of chemotherapy injury in mice,and the promotion extent was dependent on its dose.60CO ?-ray irradiation was used to build mice acute radiation injury model.Then these mice were given rhBMP-2 as therapeutic drugs through abdominal cavity injection for two weeks.The results showed that during the period of acute radiation injury the number of peripheral blood leukocyte of rhBMP-2 treated group did not quickly recover,but after acute injury,it bounced faster than the radiation control;rhBMP-2 succeeded in promoting the number of bone marrow mononuclear cells and spleen coefficient,and also could increase the percentages of CD34+ and CD45+ cells and also the gene expressions of CD34 and CD45.Colony culture in vitro showed that rhBMP-2 therapeutic group was superior to the radiation control on the numbers and cell morphology.All these results showed rhBMP-2 could promote the recovery of hematopoietic function of acute radiation injury in mice.Aplastic anemia animal model was built using 5 fluorouracil combined with busulfan,and treated them with rhBMP-2 through abdominal cavity injection for two weeks.The results showed the numbers of peripheral blood leukocyte,survival rate,the numbers of bone marrow mononuclear cells,spleen coefficient,CFU-GM colony numbers,percentage of CD34+ and CD45+ cell in bone marrow mononuclear cells and hematopoietic characterization of related indicators of rhBMP-2 treated group were still below normal values,but were significantly higher than aplastic anemia control group;the spleen histological tests also showed that the spleen function of rhBMP-2 treatment group recovered better than aplastic anemia control group.All these results showed rhBMP-2 had therapeutic effects of myelosuppression caused by aplastic anemia.All above studies preliminarily demonstrated that the rhBMP-2 has possibilities of curing hematopoietic damage caused by bone marrow inhibition,and provided experimental basis for exploring rhBMP-2 promoting hematopoiesis mechanism and new drug research.