AIIorejection remains an obstacle for successful organ transplantation. Although different types of immunosuppressive agents are effective for controlling rejection and prolonging graft survival, drug treatment is lim...AIIorejection remains an obstacle for successful organ transplantation. Although different types of immunosuppressive agents are effective for controlling rejection and prolonging graft survival, drug treatment is limited because of side effects and toxicity. Therefore, it is necessary and urgent to identify new candidate drugs for inducing allotolerance. Recently, it has been reported that bacterial flagellin induces the immunosuppressive activity of regulatory T cells （Tregs） in humans in vitro. In the present study, we analyzed the effects of recombinant flagellin （rFliC） on allograft survival and explored the underlying mechanisms associated with the activation of recipient Tregs in a murine skin allotransplantation model. The results showed that rFliC administration （3 mg/kg, once per day for 3 days, i.p.） prolonged allograft survival （mean survival time： 18.4--.1.1 days） compared to the control group （10___0.7 days, P〈O.01）. Additionally, higher positive expression of Toll-like receptor 5 （TLR5） was detected within the allograft administered with rFliC. The frequency of CD4＋CD25＋Foxp3＋ Tregs; the expression of Treg-related factors TLR5, Foxp3, TGF-I^I and IL-IO; and the proliferation and suppression of Tregs were increased following rFliC administration compared to the control. Moreover, the increased expression of tolerance-related molecules and the proliferation of Tregs induced by rFliC were attenuated by an anti-TLR5 blocking antibody both in vivo and in vitro. In conclusion, rFliC administration prolongs the survival of allografts, which is associated with the activation of recipient Tregs in a TLR5-dependent manner, rFliC may be a new candidate for anti-allorejection therapy.展开更多
Psychosocial factors are important elements in the assessment and follow-up care for vascularized composite allotransplantation(VCA) and require multidisciplinary evaluation protocols. This review will highlight diffe...Psychosocial factors are important elements in the assessment and follow-up care for vascularized composite allotransplantation(VCA) and require multidisciplinary evaluation protocols. This review will highlight differences between VCA with solid organ transplantation(SOT), provide information on the psychosocial selection of VCA candidates, ethical issues, psychological outcomes, and on the need for multicenter research. VCA is primarily a life-enhancing procedure to improve recipients' quality of life and psychological well-being and it represents a potential option to provide reproduction in case of penile or uterine transplantation. The risk benefit ratio is distinctly different than SOT with candidates desiring life enhancing outcomes including improved body image, return to occupations, restored touch, and for uterine transplant, pregnancy. The Chauvet Workgroup has been convened with membership from a number of transplant centers to address these issues and to call for multicenter research. A multicenter research network would share similar evaluation approaches so that meaningful research on psychosocial variables could inform the transplant community and patients about factors that increase risk of non-adherence and other adverse psychosocial and medical outcomes.展开更多
Spinal cord injury(SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues(aSCTs) to replace...Spinal cord injury(SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues(aSCTs) to replace lost tissues and facilitate recovery in a rat SCI model. However, rodents display considerable differences from human patients in the scale, anatomy and functions of spinal cord systems, and responses after injury. Thus, use of a large animal SCI model is required to examine the repair efficiency of potential therapeutic approaches. In this study, we transplanted allogenic aSCTs from adult dogs to the lesion area of canines after complete transection of the thoracic spinal cord, and investigated the long-term cell survival and functional recovery. To enhance repair efficiency, a growth factor cocktail was added during aSCT transplantation, providing a favorable microenvironment. The results showed that transplantation of a SCTs, in particular with the addition of growth factors, significantly improves locomotor function restoration and increases the number of neurofilament-, microtubule-associated protein2-, 5-hydroxytryptamine-, choline acetyltransferase-and tyrosine hydroxylase-positive neurons in the lesion area at 6 months post-surgery. In addition, we demonstrated that donor neurons in a SCTs can survive for a long period after transplantation. This study showed for the first time that transplanting aSCTs combined with growth factor supplementation facilitates reconstruction of injured spinal cords, and consequently promotes long lasting motor function recovery in a large animal complete transected SCI model, and therefore could be considered as a possible therapeutic strategy in humans.展开更多
文摘AIIorejection remains an obstacle for successful organ transplantation. Although different types of immunosuppressive agents are effective for controlling rejection and prolonging graft survival, drug treatment is limited because of side effects and toxicity. Therefore, it is necessary and urgent to identify new candidate drugs for inducing allotolerance. Recently, it has been reported that bacterial flagellin induces the immunosuppressive activity of regulatory T cells （Tregs） in humans in vitro. In the present study, we analyzed the effects of recombinant flagellin （rFliC） on allograft survival and explored the underlying mechanisms associated with the activation of recipient Tregs in a murine skin allotransplantation model. The results showed that rFliC administration （3 mg/kg, once per day for 3 days, i.p.） prolonged allograft survival （mean survival time： 18.4--.1.1 days） compared to the control group （10___0.7 days, P〈O.01）. Additionally, higher positive expression of Toll-like receptor 5 （TLR5） was detected within the allograft administered with rFliC. The frequency of CD4＋CD25＋Foxp3＋ Tregs; the expression of Treg-related factors TLR5, Foxp3, TGF-I^I and IL-IO; and the proliferation and suppression of Tregs were increased following rFliC administration compared to the control. Moreover, the increased expression of tolerance-related molecules and the proliferation of Tregs induced by rFliC were attenuated by an anti-TLR5 blocking antibody both in vivo and in vitro. In conclusion, rFliC administration prolongs the survival of allografts, which is associated with the activation of recipient Tregs in a TLR5-dependent manner, rFliC may be a new candidate for anti-allorejection therapy.
基金Supported by The Tirol Kliniken,Innsbruck,Austria
文摘Psychosocial factors are important elements in the assessment and follow-up care for vascularized composite allotransplantation(VCA) and require multidisciplinary evaluation protocols. This review will highlight differences between VCA with solid organ transplantation(SOT), provide information on the psychosocial selection of VCA candidates, ethical issues, psychological outcomes, and on the need for multicenter research. VCA is primarily a life-enhancing procedure to improve recipients' quality of life and psychological well-being and it represents a potential option to provide reproduction in case of penile or uterine transplantation. The risk benefit ratio is distinctly different than SOT with candidates desiring life enhancing outcomes including improved body image, return to occupations, restored touch, and for uterine transplant, pregnancy. The Chauvet Workgroup has been convened with membership from a number of transplant centers to address these issues and to call for multicenter research. A multicenter research network would share similar evaluation approaches so that meaningful research on psychosocial variables could inform the transplant community and patients about factors that increase risk of non-adherence and other adverse psychosocial and medical outcomes.
基金supported by the National Natural Science Foundation of China(81891002 and 81971178)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16040700)the National Key Research and Development Program of China(2017YFA0104701,2017YFA0104704,2016YFC1101501 and 2016YFC1101502)。
文摘Spinal cord injury(SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues(aSCTs) to replace lost tissues and facilitate recovery in a rat SCI model. However, rodents display considerable differences from human patients in the scale, anatomy and functions of spinal cord systems, and responses after injury. Thus, use of a large animal SCI model is required to examine the repair efficiency of potential therapeutic approaches. In this study, we transplanted allogenic aSCTs from adult dogs to the lesion area of canines after complete transection of the thoracic spinal cord, and investigated the long-term cell survival and functional recovery. To enhance repair efficiency, a growth factor cocktail was added during aSCT transplantation, providing a favorable microenvironment. The results showed that transplantation of a SCTs, in particular with the addition of growth factors, significantly improves locomotor function restoration and increases the number of neurofilament-, microtubule-associated protein2-, 5-hydroxytryptamine-, choline acetyltransferase-and tyrosine hydroxylase-positive neurons in the lesion area at 6 months post-surgery. In addition, we demonstrated that donor neurons in a SCTs can survive for a long period after transplantation. This study showed for the first time that transplanting aSCTs combined with growth factor supplementation facilitates reconstruction of injured spinal cords, and consequently promotes long lasting motor function recovery in a large animal complete transected SCI model, and therefore could be considered as a possible therapeutic strategy in humans.
