Chemically extracted acellular nerve allografts loaded with brain-derived neurotrophic fac- tor-transfected or ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells have been shown to repair sciat...Chemically extracted acellular nerve allografts loaded with brain-derived neurotrophic fac- tor-transfected or ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells have been shown to repair sciatic nerve injury better than chemically extracted acellular nerve allografts alone, or chemically extracted acellular nerve allografts loaded with bone marrow mesenchymal stem cells. We hypothesized that these allografts compounded with both brain-derived neurotrophic factor- and ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells may demonstrate even better effects in the repair of peripheral nerve injury. We cultured bone marrow mesenchymal stem cells expressing brain-derived neuro- trophic factor and/or ciliary neurotrophic factor and used them to treat sciatic nerve injury in rats. We observed an increase in sciatic functional index, triceps wet weight recovery rate, myelin thickness, number of myelinated nerve fibers, amplitude of motor-evoked potentials and nerve conduction velocity, and a shortened latency of motor-evoked potentials when al- lografts loaded with both neurotrophic factors were used, compared with allografts loaded with just one factor. Thus, the combination of both brain-derived neurotrophic factor and cili- ary neurotrophic factor-transfected bone marrow mesenchymal stem cells can greatly improve nerve injury.展开更多
Pretreatment of nerve allografts by exposure to irradiation or green tea polyphenols can elimi- nate neuroimmunogenicity, inhibit early immunological rejection, encourage nerve regeneration and functional recovery, im...Pretreatment of nerve allografts by exposure to irradiation or green tea polyphenols can elimi- nate neuroimmunogenicity, inhibit early immunological rejection, encourage nerve regeneration and functional recovery, improve tissue preservation, and minimize postoperative infection. In the present study, we investigate which intervention achieves better results. We produced a 1.0 cm sciatic nerve defect in rats, and divided the rats into four treatment groups： autograft, fresh nerve allograft, green tea polyphenol-pretreated （1 mg/mL, 4~C） nerve allograft, and irradiation-pre- treated nerve allograft （26.39 Gy/min for 12 hours; total 19 kGy）. The animals were observed, and sciatic nerve electrophysiology, histology, and transmission electron microscopy were carried out at 6 and 12 weeks after grafting. The circumference and structure of the transplanted nerve in rats that received autografts or green tea polyphenol-pretreated nerve allografts were similar to those of the host sciatic nerve. Compared with the groups that received fresh or irradiation-pre- treated nerve allografts, motor nerve conduction velocity in the autograft and fresh nerve allograft groups was greater, more neurites grew into the aUografts, Schwann cell proliferation was evident, and a large number of new blood vessels was observed; in addition, massive myelinated nerve fibers formed, and abundant microfilaments and microtubules were present in the axoplasm. Our findings indicate that nerve allografts pretreated by green tea polyphenols are equivalent to trans- planting autologous nerves in the repair of sciatic nerve defects, and promote nerve regeneration. Pretreatment using green tea polyphenols is better than pretreatment with irradiation.展开更多
Background Alveolar echinococcosis （AE） is caused by the metacestode stage of Echinococcus multilocularis （E. multilocularis） and is a rare but life-threatening disease. This disease commonly is characterized by a...Background Alveolar echinococcosis （AE） is caused by the metacestode stage of Echinococcus multilocularis （E. multilocularis） and is a rare but life-threatening disease. This disease commonly is characterized by an infiltrative, tumor-like growth of the E. multilocularis metacestode in the liver of human. Liver transplantation is an effective therapy for end-stage of hepatic AE, but the characteristics of host immunity associated with E. multilocularis infection with organ transplantation are poorly defined. We hereby aimed to study the immunological status and allograft heart survival in inbred rats with E. multilocularis infection. Methods Rat models of AE were established by injecting the E. multilocularis suspension made from E. multilocularis infected tissues into the abdomen of Lewis （LEW） rats. Three months later, in the experimental group, allograft heart transplantation was performed from Brown-Norway （BN） rats to the E. multilocularis infected LEW rats. In the control group, we transplanted hearts from BN rats to healthy LEW rats. The influence of the disturbed immune system in E. multilocularis infected rats on the heart transplantation was assessed, including observation of allograft heart survival time, histopathological examination of grafts and immunohistochemical examination of infiltrating cells （CD4＋ T cells, CD8＋ T cells and eosinophile granulocytes）, measurement of interleukin （IL）-4 and interferon （IFN）-γ in the serum by enzyme-linked immunosorbent assay （ELISA） and analysis of CD4＋CD25＋ regulatory T cells in peripheral blood by fluorescence activated cell sorting （FACS） flow cytometric analysis. Results The survival time of recipients in the experimental group was prolonged compared with those in the control group. The numbers of graft infiltrating CD8＋ T cells were decreased whereas the graft infiltrating eosinophil granulocytes （CD15＋） were increased in grafts in the experimental group （P 〈0.05）. Furthermore, the proportion of CD4＋CD25＋regulatory T cells in the peripheral blood was 10.8% on average in the experimental group, which was significantly higher than that in the control group （6.1%）. In addition, the level of serum IL-4 in E. multilocularis infected rats was higher than that in the control group rats, whereas the level of serum IFN-γ in experimental group was lower than that in the control group when graft rejection occurred （P 〈0.05）. Conclusions This study suggests that E. multilocularis infection could prolong the allograft survival time through the polarization of Th1/Th2-type cells and induction of CD4＋CD25＋ regulatory T cells. This strategy may provide a new idea for establishing transplantation tolerance.展开更多
文摘Chemically extracted acellular nerve allografts loaded with brain-derived neurotrophic fac- tor-transfected or ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells have been shown to repair sciatic nerve injury better than chemically extracted acellular nerve allografts alone, or chemically extracted acellular nerve allografts loaded with bone marrow mesenchymal stem cells. We hypothesized that these allografts compounded with both brain-derived neurotrophic factor- and ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells may demonstrate even better effects in the repair of peripheral nerve injury. We cultured bone marrow mesenchymal stem cells expressing brain-derived neuro- trophic factor and/or ciliary neurotrophic factor and used them to treat sciatic nerve injury in rats. We observed an increase in sciatic functional index, triceps wet weight recovery rate, myelin thickness, number of myelinated nerve fibers, amplitude of motor-evoked potentials and nerve conduction velocity, and a shortened latency of motor-evoked potentials when al- lografts loaded with both neurotrophic factors were used, compared with allografts loaded with just one factor. Thus, the combination of both brain-derived neurotrophic factor and cili- ary neurotrophic factor-transfected bone marrow mesenchymal stem cells can greatly improve nerve injury.
基金supported by grants from Research Fund of Lanzhou Military Area Command of Chinese PLA,No.CLZ12JA07Gansu Provincial Science and Technology Program,No.1208RJZA108
文摘Pretreatment of nerve allografts by exposure to irradiation or green tea polyphenols can elimi- nate neuroimmunogenicity, inhibit early immunological rejection, encourage nerve regeneration and functional recovery, improve tissue preservation, and minimize postoperative infection. In the present study, we investigate which intervention achieves better results. We produced a 1.0 cm sciatic nerve defect in rats, and divided the rats into four treatment groups： autograft, fresh nerve allograft, green tea polyphenol-pretreated （1 mg/mL, 4~C） nerve allograft, and irradiation-pre- treated nerve allograft （26.39 Gy/min for 12 hours; total 19 kGy）. The animals were observed, and sciatic nerve electrophysiology, histology, and transmission electron microscopy were carried out at 6 and 12 weeks after grafting. The circumference and structure of the transplanted nerve in rats that received autografts or green tea polyphenol-pretreated nerve allografts were similar to those of the host sciatic nerve. Compared with the groups that received fresh or irradiation-pre- treated nerve allografts, motor nerve conduction velocity in the autograft and fresh nerve allograft groups was greater, more neurites grew into the aUografts, Schwann cell proliferation was evident, and a large number of new blood vessels was observed; in addition, massive myelinated nerve fibers formed, and abundant microfilaments and microtubules were present in the axoplasm. Our findings indicate that nerve allografts pretreated by green tea polyphenols are equivalent to trans- planting autologous nerves in the repair of sciatic nerve defects, and promote nerve regeneration. Pretreatment using green tea polyphenols is better than pretreatment with irradiation.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 30760239 and No. 81160201）. Conflicts of interest： none.
文摘Background Alveolar echinococcosis （AE） is caused by the metacestode stage of Echinococcus multilocularis （E. multilocularis） and is a rare but life-threatening disease. This disease commonly is characterized by an infiltrative, tumor-like growth of the E. multilocularis metacestode in the liver of human. Liver transplantation is an effective therapy for end-stage of hepatic AE, but the characteristics of host immunity associated with E. multilocularis infection with organ transplantation are poorly defined. We hereby aimed to study the immunological status and allograft heart survival in inbred rats with E. multilocularis infection. Methods Rat models of AE were established by injecting the E. multilocularis suspension made from E. multilocularis infected tissues into the abdomen of Lewis （LEW） rats. Three months later, in the experimental group, allograft heart transplantation was performed from Brown-Norway （BN） rats to the E. multilocularis infected LEW rats. In the control group, we transplanted hearts from BN rats to healthy LEW rats. The influence of the disturbed immune system in E. multilocularis infected rats on the heart transplantation was assessed, including observation of allograft heart survival time, histopathological examination of grafts and immunohistochemical examination of infiltrating cells （CD4＋ T cells, CD8＋ T cells and eosinophile granulocytes）, measurement of interleukin （IL）-4 and interferon （IFN）-γ in the serum by enzyme-linked immunosorbent assay （ELISA） and analysis of CD4＋CD25＋ regulatory T cells in peripheral blood by fluorescence activated cell sorting （FACS） flow cytometric analysis. Results The survival time of recipients in the experimental group was prolonged compared with those in the control group. The numbers of graft infiltrating CD8＋ T cells were decreased whereas the graft infiltrating eosinophil granulocytes （CD15＋） were increased in grafts in the experimental group （P 〈0.05）. Furthermore, the proportion of CD4＋CD25＋regulatory T cells in the peripheral blood was 10.8% on average in the experimental group, which was significantly higher than that in the control group （6.1%）. In addition, the level of serum IL-4 in E. multilocularis infected rats was higher than that in the control group rats, whereas the level of serum IFN-γ in experimental group was lower than that in the control group when graft rejection occurred （P 〈0.05）. Conclusions This study suggests that E. multilocularis infection could prolong the allograft survival time through the polarization of Th1/Th2-type cells and induction of CD4＋CD25＋ regulatory T cells. This strategy may provide a new idea for establishing transplantation tolerance.
