Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs.Curren...Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs.Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection(HAR)that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the MHCⅡmolecule plays critical roles.Methods:Thus,we generate a 4-gene(GGTA1,CMAH,β4GalNT2,and CIITA)knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously.Results:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue levels.Additionally,the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping.Piglets have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without MHCⅡcan be raised in the barrier and then gradually mated in the conventional environment.Conclusions:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both MHCⅠandⅡdeletion.展开更多
Intestinal transplantation(ITx)has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies.Despite its growing cli...Intestinal transplantation(ITx)has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies.Despite its growing clinical acceptance,ITx remains among the most immunologically complex and technically demanding procedures in the field of solid organ transplantation.This review comprehensively summarizes the historical evolution,clinical indications,and advancements in surgical techniques,with emphasis on innovations in vascular anastomosis,multivisceral transplantation,and ex vivo preservation.Special attention is given to the unique immunological challenges of ITx,including bidirectional immune responses-host-vs-graft and graft-vs-host disease-immune-microbiota interactions,and the distinct roles of key immune cells.Pediatric and adult recipients exhibit divergent etiologies,immune responses,and complication profiles,necessitating individualized approaches.Although novel immunotherapeutic strategies and bioengineering innovations have improved short-term outcomes,chronic rejection,graft dysfunction,and immunosuppressive toxicity remain significant barriers.Looking ahead,future directions should prioritize precision immunomodulation,microbiome-targeted therapies,and integrated platforms for gene editing,3D bioprinting,and immune monitoring.Through multidisciplinary collaboration and translational research,ITx is poised to evolve from a high-risk salvage therapy into a personalized,sustainable solution that enhances long-term survival and patient quality of life.展开更多
Skin grafting has been used as one of the most reliable tests to determine the genetic stability of laboratory animal such as mice and rats inbred line, but no identification of swine inbred lines by skin grafting has...Skin grafting has been used as one of the most reliable tests to determine the genetic stability of laboratory animal such as mice and rats inbred line, but no identification of swine inbred lines by skin grafting has been reported. At present, Wuzhishan miniature pig （WZSP） inbred line has acquired the F24 individuals in China. In order to verify whether WZSP inbred line had D^en cultivated successfully, allogeneic skin grafts and related research were performed on F20 individuals of WZSP inbreeding population, compared with a control group of autologous transplantation. We observed the transplant recipients＇ wounds, detected peripheral blood-related indicators interleukin-2, 4 and 10, CD4~ and CD8~ lymphocytes, and conducted hematoxylin-eosin （HE） and Masson＇s staining of skin to judge whether the immune rejection reactions occurred within 28 days after transplantation. Chr. 7 genomic heterozygosity of 48 WZSP individuals from F20 to F22 was analyzed by high-density single nucleotide polymorphism （SNP） chips （60 000 SNPs）. The result showed that there were no significant differences in graft skin, the plasma interleukin-2, 4, 10, CD4~ and CD8~, HE and Masson＇s staining results between the allograft and autograft groups, and no immune rejection occurred on the allograft group. We found that 11 genes in Chr. 7 of major histocompatibility complex （MHC） I and MHC II were homozygous which confirmed that immune antibody of the allograft and autograft groups were highly identical and also provided a theoretical basis to no immune rejection occurred on the allograft in the inbred WZSP. The result proved that the WZSP inbred line had been cultivated successfully for the first time in the world. The test methods also provide a scientific basis for the identification of swine and mammal inbred lines.展开更多
Organ transplantation is the ultimate treatment for end-stage diseases such as heart and liver failure.However,the severe shortage of donor organs has limited the organ transplantation progress.Xenogeneic stem cell tr...Organ transplantation is the ultimate treatment for end-stage diseases such as heart and liver failure.However,the severe shortage of donor organs has limited the organ transplantation progress.Xenogeneic stem cell transplantation provides a new strategy to solve this problem.Researchers have shown that xenogeneic stem cell transplantation has significant therapeutic effects and broad application prospects in treating liver failure,myocardial infarction,advanced type 1 diabetes mellitus,myelosuppression,and other end-stage diseases by replacing the dysfunctional cells directly or improving the endogenous regenerative milieu.In this review,the sources,problems and solutions,and potential clinical applications of xenogeneic stem cell transplantation will be discussed.展开更多
The evolutionary emergence of an efficient immune system has a fundamental role in our survival against pathogenic attacks. Nevertheless, this same protective mechanism may also establish a negative consequence in the...The evolutionary emergence of an efficient immune system has a fundamental role in our survival against pathogenic attacks. Nevertheless, this same protective mechanism may also establish a negative consequence in the setting of disorders such as autoimmunity and transplant rejection. In light of the latter, although research has long uncovered main concepts of allogeneic recognition, immune rejection is still the main obstacle to long-term graft survival. Therefore, in order to define effective therapies that prolong graft viability, it is essential that we understand the underlying mediators and mechanisms that participate in transplant rejection. This multifaceted process is characterized by diverse cellular and humoral participants with innate and adaptive functions that can determine the type of rejection or promote graft acceptance. Although a number of mediators of graft recognition have been described in traditional immunology, recent studies indicate that defining rigid roles for certain immune cells and factors may be more complicated than originally conceived. Current research has also targeted specific cells and drugs that regulate immune activation and induce tolerance. This review will give a broad view of the most recent understanding of the allogeneic inflammatory/tolerogenic response and current insights into cellular and drug therapies that modulate immune activation that may prove to be useful in the induction of tolerance in the clinical setting.展开更多
The traditional formula of Danchai was provided by associate professor Dan Chen of Tianjin Medical University,which consisted of Chaihu(Radix Bupleuri)9 g,Baishao(Radix Paeoniae Alba)9 g,Yujin(Radix Curcumae)30 g,Muda...The traditional formula of Danchai was provided by associate professor Dan Chen of Tianjin Medical University,which consisted of Chaihu(Radix Bupleuri)9 g,Baishao(Radix Paeoniae Alba)9 g,Yujin(Radix Curcumae)30 g,Mudanpi(Cortex moutan Radicis)9 g,and Gancao(Radix glycyrrhizae)6 g.After soaking in water for 20 min,the herbs were decocted with medium heat to boiling and for 15 min with low heat.The liquid was poured out and decocted again by adding water.The decoction is mixed and consumed orally 30 min after meals,twice per day.Danchai formula can be used to treat excessive immune response-related diseases,including immune rejection after organ transplantation,autoimmune diseases,and hypersensitivity.展开更多
Heart transplantation encounters significant hurdles,prominently among them post-transplant immune rejection.[1]Present anti-rejection medications,encompassing calcineurin inhibitors(such as tacrolimus and cyclosporin...Heart transplantation encounters significant hurdles,prominently among them post-transplant immune rejection.[1]Present anti-rejection medications,encompassing calcineurin inhibitors(such as tacrolimus and cyclosporine),antimetabolites(such as mycophenolate mofetil),and corticosteroids,[2]efficiently dampen immune responses but come with inherent limitations.Prolonged usage of these medications elevates the risk of infections,metabolic complications,and potential organ damage.Despite their efficacy,these medications fall short of ensuring absolute prevention of rejection,thereby exposing recipients to potential acute or chronic rejection episodes.Furthermore,their adverse effects contribute to cardiovascular issues,renal dysfunction,and an elevated vulnerability to malignancies.[3]Ongoing innovations in immunosuppression strive to surmount these challenges by exploring novel drugs with diminished side effects or alternative approaches.The ultimate goal is to strike a delicate balance between preventing rejection and minimizing the risks inherent in prolonged immunosuppressive therapy for individuals undergoing heart transplantation.展开更多
Islet transplantation has now become a promising treatment for insulin-deficient diabetes mellitus.Compared to traditional diabetes treatments,cell therapy can restore endogenous insulin supplementation,but its large-...Islet transplantation has now become a promising treatment for insulin-deficient diabetes mellitus.Compared to traditional diabetes treatments,cell therapy can restore endogenous insulin supplementation,but its large-scale clinical application is impeded by donor shortages,immune rejection,and unsuitable transplantation sites.To overcome these challenges,an increasing number of studies have attempted to transplant hydrogel-encapsulated islet cells to treat diabetes.This review mainly focuses on the strategy of hydrogel-encapsulated pancreatic islet cells for diabetic cell therapy,including different cell sources encapsulated in hydrogels,encapsulation methods,hydrogel types,and a series of accessorial manners to improve transplantation outcomes.In addition,the formation and application challenges as well as prospects are also presented.展开更多
Background Type 1 diabetes(T1D)is a chronic autoimmune disease primarily diagnosed in childhood,characterized by pancreaticβ-cell destruction,severe insulin deficiency,and hyperglycemia.Current treatments,including i...Background Type 1 diabetes(T1D)is a chronic autoimmune disease primarily diagnosed in childhood,characterized by pancreaticβ-cell destruction,severe insulin deficiency,and hyperglycemia.Current treatments,including insulin therapy and glucose-lowering medications,manage the condition but fall short of offering a cure.In this review we explore the potential of stem-cell therapy as a transformative and curative approach for T1D,focusing on its promise in regeneratingβ-cells and addressing challenges specific to the pediatric population.Data sources A comprehensive review of the literature was conducted to evaluate stem-cell types:embryonic,perinatal,adult,induced pluripotent and cancer stem cells,and their role in T1D treatment.Particular emphasis was placed on methods forβ-cell differentiation,advancements in autologous and allogeneic stem-cell transplantation and emerging strategies to overcome safety,efficacy,and economic barriers.Challenges such as immune rejection,tumorigenicity,and cost-effectiveness were analyzed,alongside novel solutions like immune-shielding and clustered regularly interspaced short palindromic repeats(CRISPR)-CRISPR-associated protein-9(Cas9)technology.Results Stem-cell therapy presents a promising avenue for curing T1D,offering potential forβ-cell regeneration and reduced dependence on exogenous insulin.However,challenges such as delayedβ-cell functionality,immune responses,tumor risks,and high costs hinder widespread application.Conclusions Advancements in personalized medicine,immune-shielding strategies,and cost reduction may pave the way for clinical success,especially in pediatric populations.Further research addressing these barriers is essential to establish stem-cell therapy as a viable and equitable treatment option.展开更多
A successful pregnancy requires the maternal immune system to recognize and tolerate the allogeneic fetus while maintaining defense against infection both systemically and in placental tissues.At the maternal–fetal i...A successful pregnancy requires the maternal immune system to recognize and tolerate the allogeneic fetus while maintaining defense against infection both systemically and in placental tissues.At the maternal–fetal interface,the trophoblasts in the placenta play an essential role in the suppression of maternal immune rejection of the fetus.To ensure maternal–fetal tolerance and successful placentation,delicate crosstalk is established among fetus-derived trophoblasts,maternal immune cells,and decidual stromal cells(DSCs)during normal pregnancy.Decidual immune cells not only participate in the maintenance of immune tolerance but also regulate the function of trophoblasts to promote fetal growth.An imbalance in this crosstalk may lead to adverse pregnancy outcomes,such as recurrent spontaneous abortion,preeclampsia,preterm birth,intrauterine growth restriction,and infection.Here we outline some of the important discoveries in recent years related to the mechanisms by which trophoblast-derived molecules induce maternal–fetal immune tolerance.展开更多
Tissue engineering(TE)is promising for the regeneration of failed organs.However,immune rejection,shortage of seed cells,and unintegrated blood vessels restrict the development and clinical application of TE.The last ...Tissue engineering(TE)is promising for the regeneration of failed organs.However,immune rejection,shortage of seed cells,and unintegrated blood vessels restrict the development and clinical application of TE.The last factor is the most challenging and intractable.Harnessing the mature blood vessel network in existing dispensable organs could be a powerful approach to effectively overcome the obstacles.After being remodeled to harbor an immunosuppressive and proregenerative niche,these potential target organs can be transformed into other organs with specific physiological functions,compensating the latter's failed native functions.Organ transformation,such as a hepatized spleen,represents an effective and encouraging TE strategy.In this review,we discuss the current development and obstacles of TE and its feasibility and superiority in organ transformation.展开更多
In order to investigate whether the non-classi- cal HLA-G classⅠmolecule protects the porcine endothelial cells (PECs) from the lysis mediated by human immune cells in pig to human discordant xenotransplantation, we ...In order to investigate whether the non-classi- cal HLA-G classⅠmolecule protects the porcine endothelial cells (PECs) from the lysis mediated by human immune cells in pig to human discordant xenotransplantation, we have cloned HLA-G cDNA from a human placenta by RT-PCR. Mammalian expression vector, pEFG-neo, was constructed by insertion of HLA-G cDNA in pEF-neo. We obtained effi-ciently expressed PECs by stable transfection. Cytotoxicity assay showed that overexpression of HLA-G on PECs was sufficient to inhibit human NK-92 cell lysis. The level of lysis was equal to or less than that of the lysis of human umbilical vein endothelial cells mediated by human NK-92 cells. It also indicated that HLA-G inhibited the lysis of PECs mediated by xeno-antigen specific T lymphocytes. The reduction of lysis ranged between 59.1% and 88.9%. These findings sug-gest that the transgenic approach to overexpress HLA-G is believed to be a new immunotherapy in overcoming the im-mune rejections in xenotransplantion, including delayed xenograft rejection and cell-mediated rejection.展开更多
Xenotransplantation,involving animal organ transplantation into humans to address the human organ shortage,has been studied since the 17th century.Early attempts to obtain organs from animals such as goats,dogs,and no...Xenotransplantation,involving animal organ transplantation into humans to address the human organ shortage,has been studied since the 17th century.Early attempts to obtain organs from animals such as goats,dogs,and non-human primates proved unsuccessful.In the 1990s,scientists agreed that pigs were the most suitable donor animals for xenotransplantation.However,immune rejection between pig and human has hindered the application.To overcome these challenges,researchers developed genetically modified pigs that deactivate xenoreactive antigen genes and express human protective genes.These advances extended xenograft survival from days to years in non-human primates,resulting in the first human heart xenotransplant trial.Using genetically engineered pigs for the organ shortage is promising.This review provides an overview of potential incompatibilities of immunogenicity and functional proteins related to xenotransplantation between humans and pigs.Furthermore,it elucidates possible approaches for multiplex gene modification to breed better-humanized pigs for clinical xenotransplantation.展开更多
Transplantation of adult spinal cord tissue(aSCT)is a promising treatment for spinal cord injury(SCI)basing on various types of neural cells and matrix components inside aSCT.However,long-term systemic administration ...Transplantation of adult spinal cord tissue(aSCT)is a promising treatment for spinal cord injury(SCI)basing on various types of neural cells and matrix components inside aSCT.However,long-term systemic administration of immunosuppressors(e.g.tacrolimus,TAC)is required for the survival of allogeneic tissue,which often associated with severe side effects such as infection,liver damageand renal failure.In this study,a triglycerol monostearate(TGM)-based TAC delivery system(e.g.TAC@TGM)with high drug loading concentration was developed,which possessed injectable properties as well as sustainable and immune-responsive drug release behaviors.In complete transected SCI model,locally injected TAC@TGM could reduce the infiltration of inflammation cells,enhance the survival of transplanted aSCT(e.g.Tuj-1^(+)and NF^(+)neurons)and promote the recovery of locomotor function.Moreover,controlled release of TAC by TAC@TGM attenuated side effects of TAC on liver and kidneys compared with traditional systemic administration.More importantly,the developed TAC@TGM system provided a facile single dose of long-term immunosuppressive effect not just for aSCT transplantation,but also for other tissue/organ and cell transplantations.展开更多
Background AIIogeneic transplant rejection is currently a major problem encountered during organ transplantation. The dendritic cell （DC） is the most effective powerful known professional antigen-presenting cell, an...Background AIIogeneic transplant rejection is currently a major problem encountered during organ transplantation. The dendritic cell （DC） is the most effective powerful known professional antigen-presenting cell, and recent studies have found that DCs can also induce immune tolerance, and avoid or reduce the degree of transplant rejection. The aim of this study was to evaluate the effect of transfused immature CD4~ DCs on renal allografts in the rat model. Methods In this study, we induced CD4~ immature DCs from rat bone marrow cells by a cytokine cocktail. The immature CD4~ DCs were identified by morphological analysis and then the suppressive activity of these cells conditioned with donor kidney antigen was evaluated in vitro and in vivo. Results Immature CD4~ DCs conditioned with donor kidney antigen possessed immunosuppressive activity in vitro and they were able to prolong renal transplant survival in an allograft rat model in vivo. Conclusions Our study provides new information on efficacious renal transplantation, which might be useful for understanding the function of immature CD4~ DCs in modulating renal transplant rejection and improving clinical outcome in future studies.展开更多
基金National Key Research and Development Program,Grant/Award Number:2019YFA0903800,2021YFA0805701,2021YFA0805905 and 2022YFA1103603CAS Project for Young Scientists in Basic Research,Grant/Award Number:YSBR-012+2 种基金STI 2030-Major Project,Grant/Award Number:2023ZD0407503National Natural Science Foundation of China,Grant/Award Number:32071456 and 82241224Strategic Priority Research Program of the Chinese Academy of Sciences,Grant/Award Number:XDA16030000。
文摘Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs.Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection(HAR)that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the MHCⅡmolecule plays critical roles.Methods:Thus,we generate a 4-gene(GGTA1,CMAH,β4GalNT2,and CIITA)knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously.Results:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue levels.Additionally,the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping.Piglets have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without MHCⅡcan be raised in the barrier and then gradually mated in the conventional environment.Conclusions:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both MHCⅠandⅡdeletion.
基金Supported by Guangdong Provincial Medical Research Fund General Program,No.B2025209Guangzhou Science and Technology Program Project,No.2025A03J3269.
文摘Intestinal transplantation(ITx)has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies.Despite its growing clinical acceptance,ITx remains among the most immunologically complex and technically demanding procedures in the field of solid organ transplantation.This review comprehensively summarizes the historical evolution,clinical indications,and advancements in surgical techniques,with emphasis on innovations in vascular anastomosis,multivisceral transplantation,and ex vivo preservation.Special attention is given to the unique immunological challenges of ITx,including bidirectional immune responses-host-vs-graft and graft-vs-host disease-immune-microbiota interactions,and the distinct roles of key immune cells.Pediatric and adult recipients exhibit divergent etiologies,immune responses,and complication profiles,necessitating individualized approaches.Although novel immunotherapeutic strategies and bioengineering innovations have improved short-term outcomes,chronic rejection,graft dysfunction,and immunosuppressive toxicity remain significant barriers.Looking ahead,future directions should prioritize precision immunomodulation,microbiome-targeted therapies,and integrated platforms for gene editing,3D bioprinting,and immune monitoring.Through multidisciplinary collaboration and translational research,ITx is poised to evolve from a high-risk salvage therapy into a personalized,sustainable solution that enhances long-term survival and patient quality of life.
基金supported by the National High Technology Research and Development Program of China (2012AA020603)the National Transgenic Major Project, China (2008ZX08012-002-05)the National Key Technoligy R&D Program of China (2012BA13904)
文摘Skin grafting has been used as one of the most reliable tests to determine the genetic stability of laboratory animal such as mice and rats inbred line, but no identification of swine inbred lines by skin grafting has been reported. At present, Wuzhishan miniature pig （WZSP） inbred line has acquired the F24 individuals in China. In order to verify whether WZSP inbred line had D^en cultivated successfully, allogeneic skin grafts and related research were performed on F20 individuals of WZSP inbreeding population, compared with a control group of autologous transplantation. We observed the transplant recipients＇ wounds, detected peripheral blood-related indicators interleukin-2, 4 and 10, CD4~ and CD8~ lymphocytes, and conducted hematoxylin-eosin （HE） and Masson＇s staining of skin to judge whether the immune rejection reactions occurred within 28 days after transplantation. Chr. 7 genomic heterozygosity of 48 WZSP individuals from F20 to F22 was analyzed by high-density single nucleotide polymorphism （SNP） chips （60 000 SNPs）. The result showed that there were no significant differences in graft skin, the plasma interleukin-2, 4, 10, CD4~ and CD8~, HE and Masson＇s staining results between the allograft and autograft groups, and no immune rejection occurred on the allograft group. We found that 11 genes in Chr. 7 of major histocompatibility complex （MHC） I and MHC II were homozygous which confirmed that immune antibody of the allograft and autograft groups were highly identical and also provided a theoretical basis to no immune rejection occurred on the allograft in the inbred WZSP. The result proved that the WZSP inbred line had been cultivated successfully for the first time in the world. The test methods also provide a scientific basis for the identification of swine and mammal inbred lines.
基金National Natural Science Foundation of China,No.81670951.
文摘Organ transplantation is the ultimate treatment for end-stage diseases such as heart and liver failure.However,the severe shortage of donor organs has limited the organ transplantation progress.Xenogeneic stem cell transplantation provides a new strategy to solve this problem.Researchers have shown that xenogeneic stem cell transplantation has significant therapeutic effects and broad application prospects in treating liver failure,myocardial infarction,advanced type 1 diabetes mellitus,myelosuppression,and other end-stage diseases by replacing the dysfunctional cells directly or improving the endogenous regenerative milieu.In this review,the sources,problems and solutions,and potential clinical applications of xenogeneic stem cell transplantation will be discussed.
基金Supported by Sao Paulo Research Foundation-FAPESP,Nos.2012/23347-3,2014/14147-6,2012/02270-2 and CNPq
文摘The evolutionary emergence of an efficient immune system has a fundamental role in our survival against pathogenic attacks. Nevertheless, this same protective mechanism may also establish a negative consequence in the setting of disorders such as autoimmunity and transplant rejection. In light of the latter, although research has long uncovered main concepts of allogeneic recognition, immune rejection is still the main obstacle to long-term graft survival. Therefore, in order to define effective therapies that prolong graft viability, it is essential that we understand the underlying mediators and mechanisms that participate in transplant rejection. This multifaceted process is characterized by diverse cellular and humoral participants with innate and adaptive functions that can determine the type of rejection or promote graft acceptance. Although a number of mediators of graft recognition have been described in traditional immunology, recent studies indicate that defining rigid roles for certain immune cells and factors may be more complicated than originally conceived. Current research has also targeted specific cells and drugs that regulate immune activation and induce tolerance. This review will give a broad view of the most recent understanding of the allogeneic inflammatory/tolerogenic response and current insights into cellular and drug therapies that modulate immune activation that may prove to be useful in the induction of tolerance in the clinical setting.
文摘The traditional formula of Danchai was provided by associate professor Dan Chen of Tianjin Medical University,which consisted of Chaihu(Radix Bupleuri)9 g,Baishao(Radix Paeoniae Alba)9 g,Yujin(Radix Curcumae)30 g,Mudanpi(Cortex moutan Radicis)9 g,and Gancao(Radix glycyrrhizae)6 g.After soaking in water for 20 min,the herbs were decocted with medium heat to boiling and for 15 min with low heat.The liquid was poured out and decocted again by adding water.The decoction is mixed and consumed orally 30 min after meals,twice per day.Danchai formula can be used to treat excessive immune response-related diseases,including immune rejection after organ transplantation,autoimmune diseases,and hypersensitivity.
文摘Heart transplantation encounters significant hurdles,prominently among them post-transplant immune rejection.[1]Present anti-rejection medications,encompassing calcineurin inhibitors(such as tacrolimus and cyclosporine),antimetabolites(such as mycophenolate mofetil),and corticosteroids,[2]efficiently dampen immune responses but come with inherent limitations.Prolonged usage of these medications elevates the risk of infections,metabolic complications,and potential organ damage.Despite their efficacy,these medications fall short of ensuring absolute prevention of rejection,thereby exposing recipients to potential acute or chronic rejection episodes.Furthermore,their adverse effects contribute to cardiovascular issues,renal dysfunction,and an elevated vulnerability to malignancies.[3]Ongoing innovations in immunosuppression strive to surmount these challenges by exploring novel drugs with diminished side effects or alternative approaches.The ultimate goal is to strike a delicate balance between preventing rejection and minimizing the risks inherent in prolonged immunosuppressive therapy for individuals undergoing heart transplantation.
基金supported by the National Natural Science Foundation Major International(Regional)Joint Research Program(grant number 82320108003)the National Natural Science Foundation of China(grant numbers 81970717 and 82170845)+2 种基金the National Key Research and Development Program of China(grant number 2021YFA1101800)the Key Research&Development Program of Jiangsu Province(grant number BE2022853)the Research Talent Cultivation Program of Zhongda Hospital Affiliated to Southeast University(grant number CZXM-GSP-RC28).
文摘Islet transplantation has now become a promising treatment for insulin-deficient diabetes mellitus.Compared to traditional diabetes treatments,cell therapy can restore endogenous insulin supplementation,but its large-scale clinical application is impeded by donor shortages,immune rejection,and unsuitable transplantation sites.To overcome these challenges,an increasing number of studies have attempted to transplant hydrogel-encapsulated islet cells to treat diabetes.This review mainly focuses on the strategy of hydrogel-encapsulated pancreatic islet cells for diabetic cell therapy,including different cell sources encapsulated in hydrogels,encapsulation methods,hydrogel types,and a series of accessorial manners to improve transplantation outcomes.In addition,the formation and application challenges as well as prospects are also presented.
文摘Background Type 1 diabetes(T1D)is a chronic autoimmune disease primarily diagnosed in childhood,characterized by pancreaticβ-cell destruction,severe insulin deficiency,and hyperglycemia.Current treatments,including insulin therapy and glucose-lowering medications,manage the condition but fall short of offering a cure.In this review we explore the potential of stem-cell therapy as a transformative and curative approach for T1D,focusing on its promise in regeneratingβ-cells and addressing challenges specific to the pediatric population.Data sources A comprehensive review of the literature was conducted to evaluate stem-cell types:embryonic,perinatal,adult,induced pluripotent and cancer stem cells,and their role in T1D treatment.Particular emphasis was placed on methods forβ-cell differentiation,advancements in autologous and allogeneic stem-cell transplantation and emerging strategies to overcome safety,efficacy,and economic barriers.Challenges such as immune rejection,tumorigenicity,and cost-effectiveness were analyzed,alongside novel solutions like immune-shielding and clustered regularly interspaced short palindromic repeats(CRISPR)-CRISPR-associated protein-9(Cas9)technology.Results Stem-cell therapy presents a promising avenue for curing T1D,offering potential forβ-cell regeneration and reduced dependence on exogenous insulin.However,challenges such as delayedβ-cell functionality,immune responses,tumor risks,and high costs hinder widespread application.Conclusions Advancements in personalized medicine,immune-shielding strategies,and cost reduction may pave the way for clinical success,especially in pediatric populations.Further research addressing these barriers is essential to establish stem-cell therapy as a viable and equitable treatment option.
基金supported by grant number MOST 2017YFC1001400 awarded to D.-J.L.grants from the National Natural Science Foundation of China,numbers 81971456 and 81200425 awarded to X.-Q.W.grants from the National Natural Science Foundation of China,numbers 81471548 and 81490744 awarded to D.-J.L.
文摘A successful pregnancy requires the maternal immune system to recognize and tolerate the allogeneic fetus while maintaining defense against infection both systemically and in placental tissues.At the maternal–fetal interface,the trophoblasts in the placenta play an essential role in the suppression of maternal immune rejection of the fetus.To ensure maternal–fetal tolerance and successful placentation,delicate crosstalk is established among fetus-derived trophoblasts,maternal immune cells,and decidual stromal cells(DSCs)during normal pregnancy.Decidual immune cells not only participate in the maintenance of immune tolerance but also regulate the function of trophoblasts to promote fetal growth.An imbalance in this crosstalk may lead to adverse pregnancy outcomes,such as recurrent spontaneous abortion,preeclampsia,preterm birth,intrauterine growth restriction,and infection.Here we outline some of the important discoveries in recent years related to the mechanisms by which trophoblast-derived molecules induce maternal–fetal immune tolerance.
基金Fundo para o Desenvolvimento das Ciências e da Tecnologia(the Science and Technology Development Fund,Macao SAR),Grant/Award Number:FDCT 0060/2020/AGJSpanish Ministry of Health–Instituto de Salud Carlos III,Grant/Award Number:FIS PI20/00220+4 种基金Universidade de Macao(the University of Macao Research Committee),Grant/Award Number:MYRG2020‐00084‐ICMSNatural Science Foundation of Jiangsu Province,Grant/Award Number:BK20200318Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung(the Swiss National Science Foundation),Grant/Award Number:310030_185219&320030_189252the Stiftung für Leberkrankheiten(Swiss Liver Foundation)National Natural Science Foundation of China,Grant/Award Numbers:31961160701,31971309,and 32001069。
文摘Tissue engineering(TE)is promising for the regeneration of failed organs.However,immune rejection,shortage of seed cells,and unintegrated blood vessels restrict the development and clinical application of TE.The last factor is the most challenging and intractable.Harnessing the mature blood vessel network in existing dispensable organs could be a powerful approach to effectively overcome the obstacles.After being remodeled to harbor an immunosuppressive and proregenerative niche,these potential target organs can be transformed into other organs with specific physiological functions,compensating the latter's failed native functions.Organ transformation,such as a hepatized spleen,represents an effective and encouraging TE strategy.In this review,we discuss the current development and obstacles of TE and its feasibility and superiority in organ transformation.
基金This work was supported by the National Natural Science Foundation of China(Grant No.39993430)by the National?63?Project(Grant No.2001AA216071).
文摘In order to investigate whether the non-classi- cal HLA-G classⅠmolecule protects the porcine endothelial cells (PECs) from the lysis mediated by human immune cells in pig to human discordant xenotransplantation, we have cloned HLA-G cDNA from a human placenta by RT-PCR. Mammalian expression vector, pEFG-neo, was constructed by insertion of HLA-G cDNA in pEF-neo. We obtained effi-ciently expressed PECs by stable transfection. Cytotoxicity assay showed that overexpression of HLA-G on PECs was sufficient to inhibit human NK-92 cell lysis. The level of lysis was equal to or less than that of the lysis of human umbilical vein endothelial cells mediated by human NK-92 cells. It also indicated that HLA-G inhibited the lysis of PECs mediated by xeno-antigen specific T lymphocytes. The reduction of lysis ranged between 59.1% and 88.9%. These findings sug-gest that the transgenic approach to overexpress HLA-G is believed to be a new immunotherapy in overcoming the im-mune rejections in xenotransplantion, including delayed xenograft rejection and cell-mediated rejection.
基金supported by the National Key Research and Development Program of China(2022YFA1105404,2021YFF0702601 and 2021YFA0805300)the Research Unit of Generation of Large Animal Disease Models,Chinese Academy of Medical Sciences(2019I2M-5-025)+3 种基金the Science and Technology Program of Guangzhou(202201010409)the Key Research&Development Program of Hainan Province(ZDYF2021SHFZ052)the Major Science and Technology Project of Hainan Province(ZDKJ2021030)the 2020 Research Program of Sanya Yazhou Bay Science and Technology City(202002011)
文摘Xenotransplantation,involving animal organ transplantation into humans to address the human organ shortage,has been studied since the 17th century.Early attempts to obtain organs from animals such as goats,dogs,and non-human primates proved unsuccessful.In the 1990s,scientists agreed that pigs were the most suitable donor animals for xenotransplantation.However,immune rejection between pig and human has hindered the application.To overcome these challenges,researchers developed genetically modified pigs that deactivate xenoreactive antigen genes and express human protective genes.These advances extended xenograft survival from days to years in non-human primates,resulting in the first human heart xenotransplant trial.Using genetically engineered pigs for the organ shortage is promising.This review provides an overview of potential incompatibilities of immunogenicity and functional proteins related to xenotransplantation between humans and pigs.Furthermore,it elucidates possible approaches for multiplex gene modification to breed better-humanized pigs for clinical xenotransplantation.
基金supported by the Key Research and Development Program of Hunan Province(Grant Number 2021DK2003)the National Natural Science Foundation of China(Grant Number 81891000)+1 种基金Fundamental Research Funds of the Central Universities(Grant Number 521119200010)Strategic Priority Research Program of the Chinese Academy of Sciences(Grant Numbers XDA16040601,XDA16040704).
文摘Transplantation of adult spinal cord tissue(aSCT)is a promising treatment for spinal cord injury(SCI)basing on various types of neural cells and matrix components inside aSCT.However,long-term systemic administration of immunosuppressors(e.g.tacrolimus,TAC)is required for the survival of allogeneic tissue,which often associated with severe side effects such as infection,liver damageand renal failure.In this study,a triglycerol monostearate(TGM)-based TAC delivery system(e.g.TAC@TGM)with high drug loading concentration was developed,which possessed injectable properties as well as sustainable and immune-responsive drug release behaviors.In complete transected SCI model,locally injected TAC@TGM could reduce the infiltration of inflammation cells,enhance the survival of transplanted aSCT(e.g.Tuj-1^(+)and NF^(+)neurons)and promote the recovery of locomotor function.Moreover,controlled release of TAC by TAC@TGM attenuated side effects of TAC on liver and kidneys compared with traditional systemic administration.More importantly,the developed TAC@TGM system provided a facile single dose of long-term immunosuppressive effect not just for aSCT transplantation,but also for other tissue/organ and cell transplantations.
基金This study was supported by the grants from the National Natural Science Foundation of China （No. 81000230） and Science and Technology Projects in Guangdong Province （No. 2010B031600052 and No. 2011B040300021）.
文摘Background AIIogeneic transplant rejection is currently a major problem encountered during organ transplantation. The dendritic cell （DC） is the most effective powerful known professional antigen-presenting cell, and recent studies have found that DCs can also induce immune tolerance, and avoid or reduce the degree of transplant rejection. The aim of this study was to evaluate the effect of transfused immature CD4~ DCs on renal allografts in the rat model. Methods In this study, we induced CD4~ immature DCs from rat bone marrow cells by a cytokine cocktail. The immature CD4~ DCs were identified by morphological analysis and then the suppressive activity of these cells conditioned with donor kidney antigen was evaluated in vitro and in vivo. Results Immature CD4~ DCs conditioned with donor kidney antigen possessed immunosuppressive activity in vitro and they were able to prolong renal transplant survival in an allograft rat model in vivo. Conclusions Our study provides new information on efficacious renal transplantation, which might be useful for understanding the function of immature CD4~ DCs in modulating renal transplant rejection and improving clinical outcome in future studies.
