BACKGROUND：Artificial materials composed of acellular heterogeneous nerves can resolve donor shortage problems for the repair of peripheral nerve defects.However,it remains unclear whether artificial materials can ov...BACKGROUND：Artificial materials composed of acellular heterogeneous nerves can resolve donor shortage problems for the repair of peripheral nerve defects.However,it remains unclear whether artificial materials can overcome immunological rejection of heterogeneous nerve grafts and obtain similar effects as allogeneic nerve grafts.OBJECTIVE：To analyze regeneration and immunological rejection of defective sciatic nerves in rats through the use of acellular heterogeneous nerve grafts.DESIGN,TIME AND SETTING：A randomized,controlled study was performed at the Department of Anatomy,China Medical University and the Experimental Center,First Affiliated Hospital,China Medical University between January and December 2008.MATERIALS：TritonX-100 （Sigma,USA） and deoxycholate （Pierce,USA） were used.METHODS：Bilateral sciatic nerves were collected from adult rabbits and treated with TritonX-100 and sodium deoxycholate to prepare acellular sciatic nerves,which were used to bridge 1 -cm defective sciatic nerves in adult rats.MAIN OUTCOME MEASURES：The lymphocyte percentage in leukocytes was quantified following hemocyte staining.Neural regeneration and the recovery of motor end plates in the gastrocnemius muscle were observed under optical and electronic microscopy following toluidine blue staining,as well as acetylcholinesterase and succinate dehydrogenase histochemical staining.RESULTS：There was no significant difference in the lymphocyte percentage in leucocytes between transplanted and normal rats （P 〉 0.05）.At 3 months after surgery,the rat toes on the operated side were separated and the rats could walk.In addition,the footplates exhibited an escape response when acupunctured.A large number of regenerated nerve fibers were observed in the transplant group,and acetylcholinesterase-positive motor end plates were visible in fibers of the gastrocnemius muscle.CONCLUSION：Acellular heterogeneous nerve transplants for the repair of defective sciatic nerves in rats promote neural regeneration without significant immunological rejection.展开更多
BACKGROUND： At present, it has been confirmed that immunological rejection exists in the cell transplantation in brain tissue, the effects of immunosuppressant on the immunological rejection and the survival of graft...BACKGROUND： At present, it has been confirmed that immunological rejection exists in the cell transplantation in brain tissue, the effects of immunosuppressant on the immunological rejection and the survival of grafts in brain cell transplantation are worthy being investigated further. OBJECTIVE： To observe the immunological rejection after transgeneic cell transplantation in treating cerebra hemorrhage in rats, and investigate the interventional effect of cyclosprin. DESIGN ： A randomized controlled study SETTINGS： Second Affiliated Hospital of Xuzhou Medical College; First Affiliated Hospital of Nanjing Medica University. MATERIALS： Thirty-five healthy clean-degree SD rats of 6-8 weeks old were used, weighing 200-250 g, either male or female; The FACSort flow cytometer （American BD Company） and NYD-1000 image analytical system were used, The rat-anti-rat CD4 monoclonal antibody, rat-anti-rat CD8 monoclonal antibody, and rat-anti-rat MHC Ⅱ antigen monoclonal antibody were purchased from Santa Cruz Company; SP and DAB kits were purchased from Beijing Zhongshan Bio-engineering Company. XSP-8C2 light microscope was the product of Shanghai Zousun Optical Instrument, Co.,Ltd, and KYKY-3800B electron microscope was the product of China KYKY Technology Development Co.,Ltd. METHODS ： The experiments were carried out in the animal experimental center of Nanjing Medical University from April to July in 2003. ① Model establishment： The rats were anesthetized, and then the coordinates of left internal capsule were identified, and the needle was withdrawn after 120 μL blood was injected into the internal capsule. Adenoviruses were taken as the carriers, after the astrocytes were successfully transfected by nerve growth factor（NGF） gene, 0.2 mL cell suspension was injected into the sites of cerebral hemorrhage. Thirty successfully established rat models were randomly divided into cyclosporin A group （n=18） and control group, the rats were treated with intraperitoneal injection of cyclosporin A （10 mg/kg per day） intraperitoneal injection of saline of the same dosage from the 1^st day after transplantation, once a day for 7 days continuously.② CD4^＋ and CD4^＋ detection： The CD4^＋ and CD4^＋ T lymphocytes in caudal vein were counted with flow cytometer at 15 days after treatment. ③ Morphological observation in the transplanted sites： The rats were killed and then brain tissues were taken out, the transplanted sites and the structure of the normal brain tissue around the transplanted sites were observed with light and electron microscopes. ④Detections of the infiltration of T lymphocyte subsets and expression of major histocompatibility complex （MHC） Ⅱ antigen in the transplanted sites： The image analysis of immunohistochemical sections was performed with the image analytical system, and the integral optical density （IOD） was taken as the statistical value to observe the infiltration of T lymphocyte subsets and expression of MHC Ⅱ antigen in the transplanted sites, and the normal brain tissue around the transplanted sites were taken as controls. MATN OUTCOME MEASURES： ① Countings of CD4^＋ and CD4^＋ in peripheral blood; ②Results of the morphological observation in the transplanted sites; ③ Infiltration of T lymphocyte subsets and expression of MHC Ⅱ antigen in the transplanted sites RESULTS ： Totally 35 rats were used, and 30 were successfully made into models, 5 died during the treatment, the other 25 were involved in the analysis of results. ① Results of CD4^＋ and CD4^＋ T lymphocytes in pedpherel blood： The percentages of CD4^＋ and CD4^＋ T lymphocytes in the cyclosporin A group were （29.20±3.97）% and （20.65±2,02）%, respectively, which were obviously lower than those in the control group [（47,39±3,01）%, （28.30±2.36）%, t=-4.983, 4.012, P 〈 0.05], and the CDC/CD4^＋ ratio was obviously lower than that in the control group （1,41±0.86, 1,64^＋0.69, t=-3. 871, P〈 0.05）.② Morphological results in the transplanted sites： Under optical and electron microscopes, the survival region of the transplant was round, and it had an unobvious migration region with the normal brain tissues, the grafts had normal cellular form. Infiltrations of lymphocytes and monocytes were observed in both groups, and mainly located in the transplanted sites, and the expression of lymphocytes in the cyclosporin A group was markedly lower than that in the control group, and no above-mentioned changes were observed in the normal brain tissue around the transplanted sites. ③ Results of CD. and CD4^＋ T lymphocytes and expression of MHC Ⅱ antigen in the transplanted sites： The CD4^＋ and CD4^＋ T lymphocytes and expression of MHC Ⅱ antigen in the transplanted sites were observed in both groups. The IOD of CD4^＋ and CD4^＋ antigen positive cells in the cyclosporin A group were obviously lower than those in the control group （1.85±0.38, 1.44^＋0.33; 3.33±0.37, 2.648±0.56, /=-4.122, 4.434, P〈 0.05）, and the IOD of MHC Ⅱantigen positive cells was markedly lower than that in the control group （0.76±0.22, 0.94±0.24, t=3.885, P 〈 0.05）. CONCLUSION： There is immunological rejection in brain tissue after the transplantation of NSC transgeneic glial cells. ② The immunosuppressant of cyclosporin A can reduce the immunological rejection after the cell transplantation.展开更多
Over the past six decades,liver transplantation(LT)has evolved from an experimental procedure into a standardized and life-saving intervention,reshaping the landscape of organ transplantation.Driven by pioneering brea...Over the past six decades,liver transplantation(LT)has evolved from an experimental procedure into a standardized and life-saving intervention,reshaping the landscape of organ transplantation.Driven by pioneering breakthroughs,technological advancements,and a deepened understanding of immunology,LT has seen remarkable progress.Some of the most notable breakthroughs in the field include advances in immunosuppression,a revised model for end-stage liver disease,and artificial intelligence(AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT,paired with ever-evolving technological advances.Additionally,the refinement of transplantation procedures,resulting in the introduction of alternative transplantation methods,such as living donor LT,split LT,and the use of marginal grafts,has addressed the challenge of organ shortage.Moreover,precision medicine,guiding personalized immunosuppressive strategies,has significantly improved patient and graft survival rates while addressing emergent issues,such as short-term complications and early allograft dysfunction,leading to a more refined strategy and enhanced postoperative recovery.Looking ahead,ongoing research explores regenerative medicine,diagnostic tools,and AI to optimize organ allocation and posttransplantation car.In summary,the past six decades have marked a transformative journey in LT with a commitment to advancing science,medicine,and patient-centered care,offering hope and extending life to individuals worldwide.展开更多
In a groundbreaking study recently published in Nature,Kai-Shan Tao and colleagues achieved the first successful heterotopic pigto-human liver xenotransplantation using a gene-edited Bama miniature pig carrying six ta...In a groundbreaking study recently published in Nature,Kai-Shan Tao and colleagues achieved the first successful heterotopic pigto-human liver xenotransplantation using a gene-edited Bama miniature pig carrying six targeted genetic modifications designed to suppress immunologic rejection and thrombosis.1 The ability of the graft to maintain bile secretion,albumin synthesis,and histological integrity over 10 days in a brain-dead human recipient underscores the potential of xenotransplantation as a viable solution to the global shortage of donor livers for patients with acute or end-stage liver failure.展开更多
基金the Science and Technology Research Foundation of Liaoning Provincial Department of Education,No. 2008777
文摘BACKGROUND：Artificial materials composed of acellular heterogeneous nerves can resolve donor shortage problems for the repair of peripheral nerve defects.However,it remains unclear whether artificial materials can overcome immunological rejection of heterogeneous nerve grafts and obtain similar effects as allogeneic nerve grafts.OBJECTIVE：To analyze regeneration and immunological rejection of defective sciatic nerves in rats through the use of acellular heterogeneous nerve grafts.DESIGN,TIME AND SETTING：A randomized,controlled study was performed at the Department of Anatomy,China Medical University and the Experimental Center,First Affiliated Hospital,China Medical University between January and December 2008.MATERIALS：TritonX-100 （Sigma,USA） and deoxycholate （Pierce,USA） were used.METHODS：Bilateral sciatic nerves were collected from adult rabbits and treated with TritonX-100 and sodium deoxycholate to prepare acellular sciatic nerves,which were used to bridge 1 -cm defective sciatic nerves in adult rats.MAIN OUTCOME MEASURES：The lymphocyte percentage in leukocytes was quantified following hemocyte staining.Neural regeneration and the recovery of motor end plates in the gastrocnemius muscle were observed under optical and electronic microscopy following toluidine blue staining,as well as acetylcholinesterase and succinate dehydrogenase histochemical staining.RESULTS：There was no significant difference in the lymphocyte percentage in leucocytes between transplanted and normal rats （P 〉 0.05）.At 3 months after surgery,the rat toes on the operated side were separated and the rats could walk.In addition,the footplates exhibited an escape response when acupunctured.A large number of regenerated nerve fibers were observed in the transplant group,and acetylcholinesterase-positive motor end plates were visible in fibers of the gastrocnemius muscle.CONCLUSION：Acellular heterogeneous nerve transplants for the repair of defective sciatic nerves in rats promote neural regeneration without significant immunological rejection.
基金a grant from Ap-plied Basic Research Programof Jiangsu Department of Sci-ence and Technology, No.BS99062
文摘BACKGROUND： At present, it has been confirmed that immunological rejection exists in the cell transplantation in brain tissue, the effects of immunosuppressant on the immunological rejection and the survival of grafts in brain cell transplantation are worthy being investigated further. OBJECTIVE： To observe the immunological rejection after transgeneic cell transplantation in treating cerebra hemorrhage in rats, and investigate the interventional effect of cyclosprin. DESIGN ： A randomized controlled study SETTINGS： Second Affiliated Hospital of Xuzhou Medical College; First Affiliated Hospital of Nanjing Medica University. MATERIALS： Thirty-five healthy clean-degree SD rats of 6-8 weeks old were used, weighing 200-250 g, either male or female; The FACSort flow cytometer （American BD Company） and NYD-1000 image analytical system were used, The rat-anti-rat CD4 monoclonal antibody, rat-anti-rat CD8 monoclonal antibody, and rat-anti-rat MHC Ⅱ antigen monoclonal antibody were purchased from Santa Cruz Company; SP and DAB kits were purchased from Beijing Zhongshan Bio-engineering Company. XSP-8C2 light microscope was the product of Shanghai Zousun Optical Instrument, Co.,Ltd, and KYKY-3800B electron microscope was the product of China KYKY Technology Development Co.,Ltd. METHODS ： The experiments were carried out in the animal experimental center of Nanjing Medical University from April to July in 2003. ① Model establishment： The rats were anesthetized, and then the coordinates of left internal capsule were identified, and the needle was withdrawn after 120 μL blood was injected into the internal capsule. Adenoviruses were taken as the carriers, after the astrocytes were successfully transfected by nerve growth factor（NGF） gene, 0.2 mL cell suspension was injected into the sites of cerebral hemorrhage. Thirty successfully established rat models were randomly divided into cyclosporin A group （n=18） and control group, the rats were treated with intraperitoneal injection of cyclosporin A （10 mg/kg per day） intraperitoneal injection of saline of the same dosage from the 1^st day after transplantation, once a day for 7 days continuously.② CD4^＋ and CD4^＋ detection： The CD4^＋ and CD4^＋ T lymphocytes in caudal vein were counted with flow cytometer at 15 days after treatment. ③ Morphological observation in the transplanted sites： The rats were killed and then brain tissues were taken out, the transplanted sites and the structure of the normal brain tissue around the transplanted sites were observed with light and electron microscopes. ④Detections of the infiltration of T lymphocyte subsets and expression of major histocompatibility complex （MHC） Ⅱ antigen in the transplanted sites： The image analysis of immunohistochemical sections was performed with the image analytical system, and the integral optical density （IOD） was taken as the statistical value to observe the infiltration of T lymphocyte subsets and expression of MHC Ⅱ antigen in the transplanted sites, and the normal brain tissue around the transplanted sites were taken as controls. MATN OUTCOME MEASURES： ① Countings of CD4^＋ and CD4^＋ in peripheral blood; ②Results of the morphological observation in the transplanted sites; ③ Infiltration of T lymphocyte subsets and expression of MHC Ⅱ antigen in the transplanted sites RESULTS ： Totally 35 rats were used, and 30 were successfully made into models, 5 died during the treatment, the other 25 were involved in the analysis of results. ① Results of CD4^＋ and CD4^＋ T lymphocytes in pedpherel blood： The percentages of CD4^＋ and CD4^＋ T lymphocytes in the cyclosporin A group were （29.20±3.97）% and （20.65±2,02）%, respectively, which were obviously lower than those in the control group [（47,39±3,01）%, （28.30±2.36）%, t=-4.983, 4.012, P 〈 0.05], and the CDC/CD4^＋ ratio was obviously lower than that in the control group （1,41±0.86, 1,64^＋0.69, t=-3. 871, P〈 0.05）.② Morphological results in the transplanted sites： Under optical and electron microscopes, the survival region of the transplant was round, and it had an unobvious migration region with the normal brain tissues, the grafts had normal cellular form. Infiltrations of lymphocytes and monocytes were observed in both groups, and mainly located in the transplanted sites, and the expression of lymphocytes in the cyclosporin A group was markedly lower than that in the control group, and no above-mentioned changes were observed in the normal brain tissue around the transplanted sites. ③ Results of CD. and CD4^＋ T lymphocytes and expression of MHC Ⅱ antigen in the transplanted sites： The CD4^＋ and CD4^＋ T lymphocytes and expression of MHC Ⅱ antigen in the transplanted sites were observed in both groups. The IOD of CD4^＋ and CD4^＋ antigen positive cells in the cyclosporin A group were obviously lower than those in the control group （1.85±0.38, 1.44^＋0.33; 3.33±0.37, 2.648±0.56, /=-4.122, 4.434, P〈 0.05）, and the IOD of MHC Ⅱantigen positive cells was markedly lower than that in the control group （0.76±0.22, 0.94±0.24, t=3.885, P 〈 0.05）. CONCLUSION： There is immunological rejection in brain tissue after the transplantation of NSC transgeneic glial cells. ② The immunosuppressant of cyclosporin A can reduce the immunological rejection after the cell transplantation.
文摘Over the past six decades,liver transplantation(LT)has evolved from an experimental procedure into a standardized and life-saving intervention,reshaping the landscape of organ transplantation.Driven by pioneering breakthroughs,technological advancements,and a deepened understanding of immunology,LT has seen remarkable progress.Some of the most notable breakthroughs in the field include advances in immunosuppression,a revised model for end-stage liver disease,and artificial intelligence(AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT,paired with ever-evolving technological advances.Additionally,the refinement of transplantation procedures,resulting in the introduction of alternative transplantation methods,such as living donor LT,split LT,and the use of marginal grafts,has addressed the challenge of organ shortage.Moreover,precision medicine,guiding personalized immunosuppressive strategies,has significantly improved patient and graft survival rates while addressing emergent issues,such as short-term complications and early allograft dysfunction,leading to a more refined strategy and enhanced postoperative recovery.Looking ahead,ongoing research explores regenerative medicine,diagnostic tools,and AI to optimize organ allocation and posttransplantation car.In summary,the past six decades have marked a transformative journey in LT with a commitment to advancing science,medicine,and patient-centered care,offering hope and extending life to individuals worldwide.
基金supported by the KRIBB Research Initiative Program(KGM4252533,PRM2122523,KGM5162524)the National Research Council of Science&Technology(NST)grant funded by the Korea government(MSIT)(No.GTL24021-000).
文摘In a groundbreaking study recently published in Nature,Kai-Shan Tao and colleagues achieved the first successful heterotopic pigto-human liver xenotransplantation using a gene-edited Bama miniature pig carrying six targeted genetic modifications designed to suppress immunologic rejection and thrombosis.1 The ability of the graft to maintain bile secretion,albumin synthesis,and histological integrity over 10 days in a brain-dead human recipient underscores the potential of xenotransplantation as a viable solution to the global shortage of donor livers for patients with acute or end-stage liver failure.
