ABSTRACT
Resumen El trasplante pulmonar implica una serie de desafíos, que como lo ha demostrado la historia, no sólo depende de un adecuado desarrollo de técnicas quirúrgicas, sino también de la comprensión de una serie de complejas interacciones inmunológicas celulares y humorales que serán las responsables del tipo de respuesta (innata y/o adquirida) fisiológica y que pudiesen desencadenar las complicaciones asociadas al trasplante (rechazo hiperagudo, agudo o crónico). Cada una de las cuales tiene su potencial prevención y/o tratamiento. El poder conocer esta serie de respuestas, permite al clínico anticiparse a algunos de estos eventos y evitar de mejor forma el daño y las consecuencias que pueden producir en los casos de trasplante pulmonar.
Lung transplantation involves a series of challenges, which as history has shown, depends not only on an adequate development of surgical techniques, but also on the understanding of a series of complex cellular and humoral immunological interactions that will be responsible for the type of physiological response (innate - acquired) and that could trigger the complications associated with transplantation (hyperacute, acute or chronic rejection). Each of which has its potential prevention and treatment. Being able to know this series of responses, allows the clinician to anticipate some of these events and to avoid in a better way the damage and the consequences that can occur in cases of lung transplantation.
Subject(s)
Humans , Transplantation Immunology/immunology , Lung Transplantation , Graft Rejection/immunology , T-Lymphocytes/immunology , Autoimmunity , Nuclear Factor 45 Protein , Graft Rejection/prevention & control , Immunity, Cellular , Immunity, Innate , Immunosuppressive AgentsABSTRACT
In recent years, the science and technology of organ transplantation have developed rapidly, which has been widely applied worldwide. However, multiple challenges remain to be resolved by clinicians, such as functional damage and immune rejection of transplant organs, immune deficiency caused by extensive use of immunosuppressants, chronic allograft dysfunction and adverse reactions. This article introduced relevant key research results published in 2021, taking the function and mechanism of immune cell subsets in the process of organ transplantation rejection or immune tolerance, and the research and application of new materials and drugs in organ transplantation as the main clues. The latest research progresses on regional immune response, especially the application of tissue-resident memory T cell in organ transplantation, were briefly summarized, and the future development of transplantation immunology was prospected.
ABSTRACT
The American Transplant Congress (ATC) is an influential academic congress in the field of organ transplantation. In this article, the hotspots of liver transplantation in 2020 ATC were summarized, including the latest research progress in donor liver procurement and quality assessment, donor liver preservation and ischemia-reperfusion injury (IRI), liver transplantation for hepatocellular carcinoma and other hepatic malignancies, complications after liver transplantation, transplantation immunology, perioperative management and donor-derived infection, pediatric liver transplantation and cell therapy, etc.
ABSTRACT
Introducción. El trasplante de intestino mejora la supervivencia de pacientes con falla intestinal secundaria al síndrome de intestino corto. Estos receptores tienen gran riesgo de rechazo agudo, por lo cual, de manera protocolaria y como método de referencia, se practican biopsias intestinales. En este reporte de caso se hizo el seguimiento inmunológico de anticuerpos anti-HLA por tecnología Luminex™ (LSA) de un paciente con trasplante de intestino más biopsias por protocolo para un diagnóstico temprano, y una adecuada correlación histológica. Presentación del caso. Se trata de un paciente de 20 años de edad con síndrome de intestino corto, que ingresó a la Fundación Valle del Lili (Cali, Colombia) y requirió un trasplante aislado de intestino. El seguimiento inmunológico se hizo con tecnología Luminex™ y biopsias intestinales mensuales. Según la tamización contemplada en el protocolo previo al trasplante, el paciente tuvo anticuerpos anti-HLA (PRA de clase I y II) negativos; y a los 11 meses después del trasplante, los anticuerpos anti-HLA de clase I y II fueron positivos. Con la prueba de LSA se detectó un anticuerpo específico contra donantes (Donor Specific Antibodies, DSA) y varios anticuerpos contra otros subtipos moleculares. Se tomó una biopsia que mostró un leve rechazo celular agudo y se inició tratamiento con plasmaféresis. Hasta 21 meses después del trasplante, el paciente no ha presentado rechazos clínicos y ha tenido una adecuada evolución clínica y paraclínica Conclusión. Este es el primer trasplante de intestino en nuestro centro, en el que se hace seguimiento inmunológico con tecnología Luminex™. Consideramos que la detección con DSA es un buen marcador de rechazo agudo humoral, que permitiría una aproximación diagnóstica y una intervención oportuna
Background: Small bowel transplant improves survival of the recipients that have intestinal failure secondary to short bowel syndrome. These patients have a high risk of acute rejection; for this reason bowel biopsies are performed as protocol and is the gold standard. Immunological follow-up of anti-HLA antibodies with Luminex® technology (LSA) was carried out in a patient with intestinal transplant and biopsies were performed to achieve an early diagnosis and a suitable histological correlation. Case report: A 20-year-old patient with short bowel syndrome secondary to extensive intestinal resection due to a complicated appendicitis underwent isolated bowel transplantation. The post-transplant immunological follow-up was performed with LSA and monthly intestinal biopsies. Antibodies with mean fluorescence intensity greater than 1500 were positive. During the pre-transplant protocol, the patient was screened for anti-HLA antibodies with negative results. Eleven months post-transplant, the screening test for anti-HLA Class I and II antibodies was positive; the specificity of the LSA test detected one specific donor antibody (DSA) and several antibodies against other molecular subtypes. The biopsy result was a mild acute cellular rejection and plasmapheresis therapy was started. The patient has not presented a clinical rejection, and at 21 months post-transplantation exhibits an adequate clinical and paraclinical evolution. Conclusions: This is the first small bowel transplant where immunological follow-up is done with LSA. We believe that the detection of DSA is a marker of acute humoral rejection that allows a diagnostic approach and a timely intervention
Subject(s)
Humans , Organ Transplantation , Graft Rejection , Histocompatibility Antigens , HLA Antigens , Transplantation ImmunologyABSTRACT
Background The conventional drugs for preventing and treating graft rejection have the risks of inducing adverse responses.Researches showed that resolvinE1 (RvE1) can regulate Th1 cell-mediated immunoreaction.However,whether RvE1 has an inhibit effect on high-risk corneal graft is unclear now.Objective This study was to investigate the effects of RvE1 on immune rejection in high-risk corneal grafting mouse models.Methods SPF BALB/c mice were used as recipients,C57BL/6 mice were as donors.Ninety BALB/c mice were divided into corneal allograft group,corneal allograft+RvE1 group and corneal autograft group according to random number table.High-risk corneal graft models were established by corneal suturing for 14 days and followed by penetrating keratoplasty in recipients.Allograft keratoplasty was performed on the right eyes in the mice of corneal allograft group and corneal allograft+RvE1 group,and self-corneal graft rotated 180°was transplanted on the right eyes in the mice of autograft group.Normal saline solution of 10 μl was subconjunctivally injected after surgery once per day for 7 days in the corneal allograft group and corneal autograft group,and 10 μl RyE1 (1 μg) was used in the same way in the corneal allograft+RvE1 group.The recipient eyes were examined for potential rejection signals with slit lamp microscope and calculated the mean survival time and rejection index (RI).The histopathology was examined 21 days after modeling by hemotoxylin and eosin staining.The expressions of CD4 and interferon-γ (IFN-γ)in the corneas were detected by immunohistochemistry.Th1 cell (CD3+CD8a-IFN-γ+) percentage in draining lymph nodes were measured by flow cytometry.The mRNA expression levels of interleukin-2 (IL-2),tumor mecrosis factor-α (TNF-α),IFN-γ and T-bet were detected by real-time fluorescence quantitative PCR.Results The mean survival time of grafts was (28.5± 1.7) days in the corneal allograft group,and that in the corneal allograft+RvE1 group was (14.0±1.6) days,showing a significant difference between them (t =4.14,P<0.001),while the survival rate was 100% at 50 days after modeling in the corneal autograft group.Corneal edema and inflammatory cell infiltration were slight in the corneal allograft+RvE1 group and corneal autograft group compared with corneal allograft group.CD4 was positively expressed in corneal tissue,and IFN-γ was expressed in corneal epithelium.The CD4+ and IFN-γ+ cell number was decreased in the corneal allograft+RvE1 group and corneal autograft group compared with corneal allograft group under the fluorescence microscope.The percentages of Th1 cells in lymph cells of corneal allograft +RvE1 group and corneal autograft group were (1.07 ±0.25) %,(0.85 ±0.12) %,respectively,which were significnatly lower than (1.56±0.20) % in the corneal allograft group (both at P<0.05).The expressions of IL-2,TNF-α,IFN-γ and T-bet mRNA in the corneal tissue in the corneal allograft group were higher than those in the corneal allograft+RvE1 group and corneal autograft group (all at P<0.05).Conclusions RyE1 inhibits graft rejection in high-risk allograft mouse models probably by down-regulating the Th1 cell percentage in lymph cells and the expression of inflammationrelated cytokines in corneal grafts.
ABSTRACT
<p><b>Background </b>: Shigyakusan, a 4-component Japanese herbal medicine (Paeoniae radix, Aurantii fructus immaturus, Glycyrrhizae radix and Bupleuri radix), is used not only for cholecystitis and gastritis as an antiinflammatory agent, but also for anxiety neurosis and insomnia as an anti-anxiety agent.<br><b>Methods </b>: We investigated the effects of shigyakusan on alloimmune responses in fully MHC-mismatched murine cardiac allograft transplantation. CBA mice underwent transplantation of a C57BL/6 heart and received shigyakusan or one component of shigyakusan administered orally from the day of transplantation until 7 days afterward. Histologic studies, cytokine measurements, and flow cytometry assessments were performed.<br><b>Results </b>: Untreated CBA recipients acutely rejected C57BL/6 cardiac grafts (median survival times [MST], 7 days). On the other hand, CBA transplant recipients given shigyakusan had significantly prolonged C57BL/6 allograft survival (MST, 22.5 days). MSTs for C57BL/6 transplant recipients given Paeoniae radix, Aurantii fructus immaturus, Glycyrrhizae radix and Bupleuri radix were 11, 9.5, 18.5 and 8 days, respectively. Additionally, flow cytometry studies showed that the percentage of CD25+Foxp3+ cell populations in CD4+ cells was increased in transplant recipients given shigyakusan.<br><b>Conclusion </b>: Shigyakusan induced hyporesponsiveness to fully MHC-mismatched allogeneic cardiac allografts and may generate CD4+CD25+Foxp3+ cells in our model.</p>
ABSTRACT
Intestinal transplantation has shown exceptional growth over the past 10 years. At the end of the 1990’s, intestinal transplantation moved out of the experimental realm to become a routine practice in treating patients with severe complications related to total parenteral nutrition and intestinal failure. In the last years, several centers reported an increasing improvement in survival outcomes (about 80%), during the first 12 months after surgery, but long-term survival is still a challenge. Several advances led to clinical application of transplants. Immunosuppression involved in intestinal and multivisceral transplantation was the biggest gain for this procedure in the past decade due to tacrolimus, and new inducing drugs, mono- and polyclonal anti-lymphocyte antibodies. Despite the advancement of rigid immunosuppression protocols, rejection is still very frequent in the first 12 months, and can result in long-term graft loss. The future of intestinal transplantation and multivisceral transplantation appears promising. The major challenge is early recognition of acute rejection in order to prevent graft loss, opportunistic infections associated to complications, post-transplant lymphoproliferative disease and graft versus host disease; and consequently, improve results in the long run.
O transplante de intestino, ao redor do mundo, tem crescido de maneira sólida e consistente nos últimos 10 anos. No final da década de 1990, passou de um modelo experimental para uma prática clínica rotineira no tratamento dos pacientes com complicação severa da nutrição parenteral total com falência intestinal. Nos últimos anos, vários centros têm relatado uma crescente melhora nos resultados de sobrevida do transplante no primeiro ano (ao redor de 80%), porém, a longo prazo, ainda é desafiador. Diversos avanços permitiram sua aplicação clínica. O surgimento de novas drogas imunossupressoras, como o tacrolimus, além das drogas indutoras, os anticorpos antilinfocíticos mono e policlonal, nos últimos 10 anos, foi de suma importância para a melhora da sobrevida do transplante de intestino/multivisceral, mas, apesar dos protocolos bastante rígidos de imunossupressão, a rejeição é bastante frequente, podendo levar a altas taxas de perdas de enxerto a longo prazo. O futuro do transplante de intestino e multivisceral parece promissor. O grande desafio é reconhecer precocemente os casos de rejeição, prevenindo a perda do enxerto e melhorando os resultados a longo prazo, além das complicações causadas por infecções oportunistas, doenças linfoproliferativas pós-transplante e a doença do enxerto contra hospedeiro.
Subject(s)
Humans , Intestines/transplantation , Organ Transplantation/trends , Viscera/transplantation , Graft Survival , Liver TransplantationABSTRACT
BACKGROUND:Aortic root homograft has been widely used, but it stil has a high incidence of calcification and degeneration after operation. OBJECTIVE:To investigate the alteration of biological and immunological properties of rabbit aortic root homograft treated with de-endothelialization and decellularization methods, and to find a better decellularization method. METHODS:Aortic root homografts obtained from rabbits were randomly divided into fresh group, de-endothelialization group, and decellularization group. The morphology of homografts was evaluated by hematoxylin-eosin, Masson and VG stainings. The biological properties such as thickness, tensile strength, broken extension rate, and heat shrinkage temperature were detected. The immunological features (inflammatory cellinfiltration, calcium content and CD152 expression) were determined with immunohistochemistry and flame atomic absorption spectrometry. RESULTS AND CONCLUSION:As demonstrated in morphological observation, protocols of de-endothelialization and decellularization methods we used attained our desired aim of decellularization perfectly. Tensile strength and broken extension rate of decellularization group were decreased significantly compared with fresh group (P0.05). Hematoxylin-eosin staining showed that, inflammatory reaction was the most apparent in fresh group, showing a large amount of inflammatory cells infiltration;compared with fresh group, inflammatory reaction was significantly attenuated in de-endothelialization group, the number of inflammatory cells was significantly decreased. The inflammatory reaction was the lowest in the decellularization group, only inflammatory cells infiltrated the tissue edge. Immunohistochemistry showed that, CD152 expression was significantly increased in de-endothelialization and decellularization groups compared with fresh group (P<0.05). Calcium content in de-endothelialization and decellularization groups was significantly decreased compared with fresh group (P<0.05). It could be concluded that the immunogenicity of de-endothelialized and decellularized aortic homografts is decreased significantly, and the de-endothelialization method could better maintain the tensile property.
ABSTRACT
With the rapid development of the individual medical care in the 21st century,based on the quick advancement of the preclinical immunology as well as the relevant bioscience technology,the application of clinical immunological diagnostic inspection has been involved in multiple diseases,including the investigation of the pathology,diagnosis,selection of the treatment regime and the evaluation of the therapy efficacy.Along with the further research,novel means of the treatment and the inspection technology have been to be utilized or explored.The focus should be concentrated on the utilization of the new technologies,new ways of the clinical immunological inspection,improving the fabric of the knowledge and the application ability of the professionals in this major,in order to provide effective service to the clinical medical care and the health of the patients.
ABSTRACT
In the last 10 years, mesenchymal stem cells (MSCs) have emerged as a therapeutic approach to regenerative medicine, cancer, autoimmune diseases, and many more due to their potential to differentiate into various tissues, to repair damaged tissues and organs, and also for their immunomodulatory properties. Findings in vitro and in vivo have demonstrated immune regulatory function of MSCs and have facilitated their application in clinical trials, such as those of autoimmune diseases and chronic inflammatory diseases. There has been an increasing interest in the role of MSCs in allogeneic hematopoietic stem cell transplantation (HSCT), including hematopoietic stem cell engraftment and the prevention and treatment of graft-versus-host disease (GVHD), and their therapeutic potential has been reported in numerous clinical trials. Although the safety of clinical application of MSCs is established, further modifications to improve their efficacy are required. In this review, we summarize advances in the potential use of MSCs in HSCT. In addition, we discuss their use in clinical trials of the treatment of GVHD following HSCT, the immunomodulatory capacity of MSCs, and their regenerative and therapeutic potential in the field of HSCT.
Subject(s)
Animals , Humans , Chimerism , Clinical Trials as Topic , Graft vs Host Disease/immunology , Hematopoietic Stem Cell Transplantation , Immunomodulation , Mesenchymal Stem Cells/cytologyABSTRACT
Objective To study the efficacy of hypo responsiveness of allogenic T cells induced by curcumin (Cur)-treated dendritic cells (DCs) and influence on survival time of renal allografts in rats.Methods DCs were generated from Wistar rat bone marrow and treated with Cur. The costimulatory molecules (CDl1c, CD80, CD86 and major histocompability complex Ⅱ ) were determined by using flow cytometry,and the production of IL-12 in DCs culture supernatant was examined by using ELISA.The probability of Cur treated DCs to stimulate the proliferation of Lewis rat T cells was detected by using mixed leukocyte reaction (MLR),and the antigen specific T cell hypo responsiveness was analyzed by using secondary MLR. Allograft renal transplantation animal models were established by using Wistar rats as donors,and Lewis rats as recipients.At 7th day before allograft renal transplantation,Cur-treated DCs from donors were injected into recipients through tail vein, meanwhile the non-treated control group and immature DCs control group (immature DCs from donors were injected into recipients through tail vein) were set up.The allograft survival time and allograft pathology after transplantation were assayed.Reaction of T cells from the recipients to mature DCs of donors was analyzed at 14th day.Results Cur restrained the expression of DCs phcnotypc and production of IL-12 (P<0.05). Cur treated DCs displayed poor ability to stimulate T cells proliferation,and potential to induce antigen specific T cell hypo-responsiveness.The survival time of the renal allograft in Cur-treatcd CDs group [(31.5 ± 6.9) days] was significantly longer (P<0.05) than in control group [(8.6± 2.1) days] and immature DCs control group [(22.4± 7.4) days],and the pathological lesions in the renal allografts in Cur treated CDs group were milder than in the control group and immature DCs control group.T cells from the recipients injected with Cur-treated DCs showed significant hypo-responsiveness to mature DCs from donors (P<0.05),but higher proliferation ability to the stimulation of third party independent antigen.Conclusion Cur can suppress the maturation and function of DCs,and induce immune suppression of allogeneic T cells,while infusion of Cur-treated immature DCs can prolong the survival of renal allograft remarkably.
ABSTRACT
Objective To study whether the viral metabolites can make influence on biological behavior of mesenchymal stem cells (MSCs) and to provide evidence for safe MSCs transplantation.Methods MSCs were isolated from bone marrow of C57BL/6 mice and the mRNA level of Toll like receptor 3 (TLR3)was detected.In vitro polyinosinic-polycytidylic acid [poly(I ∶ C)] was used as the product of viral metabolite to stimulate MSCs.We recorded the change of MSCs in terms of self-renewal,multi-directional differentiation,directional migration and immunosuppression by flow cytometry,PCR etc.Results ①Low-expressed TLR3 mRNA was dectected in MSCs and it was upregulated after being stimulated by poly(I ∶ C).②After being stimulated by poly(I ∶ C)for 24,48,and 72 hours,the self-renewal ability of MSCs had no statistical difference with that of the control group(P >0.05).However,poly (I ∶ C)promoted the differentiation of MSCs to lipoblast and osteoblast (P < 0.01).③The directional migration ability of MSCs was weakened significantly by poly(I ∶ C) stimulation.After being stimulated for 6,12,and 24 hours,the migration rate of MSCs was(82.83 ± 1.69) %,(87.80 ± 3.58) %,and (92.67 ± 2.52) % respectively compared to that of the control group.The difference had statistical significance(P <0.01).④MSCs had great immunological suppression ability and it was dependant on the number of MSCs.After being stimulated by poly(I ∶ C),the ability of MSCs' immunological suppression on proliferation of activated splenocytes was not impaired and the difference had no statistical significance compared with that of the control group(P >0.05).Conclusion While maintaining the viability and immunosuppression function of MSCs,viral metabolite inhibits migration of MSCs,holds them in the transplanted position and protects the graft,providing evidence for MSCs as seed cells in the treatment of diabetes and other immune disorder diseases.
ABSTRACT
Tokishakuyakusan is a Japanese herbal medicine which is extracts from six herbal materials. The author investigated the effects of oral administration of Tokishakuyakusan in a murine model of cardiac transplantation with fully mismatched allografts. CBA mice (H 2k) underwent transplantation of C 57 BL/6 (H 2b) hearts and received oral administration of Tokishakuyakusan from day 0 to day 7 after grafting. Untreated CBA mice rejected C 57 BL/6 cardiac grafts acutely (median survival time [MST], 7 days). Mice given 2 g/kg/day of Tokishakuyakusan accepted their grafts (MST, 60 days). However, each herbal material alone and 0.2, 0.02 g/kg/day of Tokishakuyakusan did not prolong the allografts survival. Splenocytes from Tokishakuyakusan-treated recipients showed alloproliferative hyporesponsiveness and down-regulation of IFN-γ in mixed leukocyte culture with C 57 BL/6 stimulators. Secondary CBA recipients (naive) given whole splenocytes from primary Tokishakuyakusan-treated CBA recipients with C 57 BL/6 cardiac allografts 30 days after grafting had prolonged survival of C 57 BL/6 hearts (MST, 100 days) compared to that in the secondary recipients with adoptive transfer of naive splenocytes (MST, 12 days). In flow cytometry experiment, the population of CD 4+CD 25+cells, CD 4+FOXP 3+cells and CD 25+FOXP 3+cells were increased in the spleens of Tokishakuyaku-san-treated CBA recipients. Treatment with Tokishakuyakusan induced unresponsiveness to fully allogeneic cardiac allograft and generated regulatory cells. Traditional knowledge of Japanese herbal medicine may contribute to immunomodulation after modern transplantation surgery.
ABSTRACT
Hematopoietic chimerism is a measure of the number of donor and recipient cells in the host following hematopoietic stem cell transplantation (HSCT), and it has a good correlation with GVHD and relapse. Chimerism detection after nonmyeloablative allo-HSCT is a simple essential and effective method to predict the outcome of the disease, and can significantly improve the success rate of transplants, reduce the recurrence and then improve the quanlity of life of patients.
ABSTRACT
Transplantation would be the only way to cure the end-stage organ failure involving heart, lung, liver, kidney and pancreas. The replacement of the parts of the body damaged to lose its function or lost to trauma must be a dream of human-being. Human history is replete with chimeras, from sphinxes to mermaids, making one wonder if the ancients might actually have dreamed of what now is called 'xenotransplantation'. In the 20th century, the transplantation of organs and tissues to cure disease has become a clinical reality. The development in the fields of surgical techniques, physiology and immunology attributed to the successful transplantation in human. In the center of the successful transplantation lies the progress in understanding the cellular and molecular biology of immune system which led to the development of immunosuppressive drugs and the invention of the concept of immunological tolerance. The mandatory side effects of immunosuppressive drugs including infection and cancer forced us to search alternative approaches along with the development of new immunosuppressive agents. Among the alternative approaches, the induction of a state of immunologic tolerance would be the most promising and the most generic applicability as a future therapy. Recent reports documenting long-term graft survival without immunosuppression suggest that tolerance-based therapies may become a clinical reality. Last year, we saw the epoch making success of overcoming hyperacute rejection in porcine to primate xenotransplantation which will lead porcine to human xenotransplantation to clinical reality. In this review, I dare to summarize the development of transplantation immunology from the perspective of history.
Subject(s)
Humans , Allergy and Immunology , Chimera , Graft Survival , Heart , Immune System , Immunosuppression Therapy , Immunosuppressive Agents , Inventions , Kidney , Liver , Lung , Molecular Biology , Pancreas , Physiology , Primates , Transplantation Immunology , Transplantation, HeterologousABSTRACT
To study the mechanism of inhibition and the effective concentration of HCPT in treatment of acute allgraft rejection, we made an in vitro model using mixed lymphocyte culture (MLC) with the stimulator lymphocytes from SD rats and the responder ones from Wistar rats. We observed the results of the inhibitory effect of HCPT on the reaction of the lymphocytic proliferation as well as the dose-effect relationship of HCPT. The results showed that HCPT at concentrations of 100?g/ml, 10?g/ml and 2?g/ml inhibited the proliferative reaction significantly, the inhibition index were 0. 734 ? 0. 085, 0. 537?0. 361 and 0. 503 ? 0. 225, respectively. The efficacy of 100?g/ml HCPT was significantly higher that of than that of both 10?g/ml (P
ABSTRACT
Objective To comprehensively summarize the recent development of organ transplantation specialty,and raise a suggestion for the future progress of the subject.Methods The info investigation method was employed to retrieve the literature concerning solid organ transplantation published in recent five years domestically and abroad,and the new progresses were analyzed on organ transplantation in both military and civil fields,and also fundamental and clinical researches.Results Researches on organ transplantation had progressed rapidly on foundation and clinical application in recent 5years in armed forces.The major achievements were in immune recognition and adjustment,transplant immune tolerance,the regulating effect of CTLA4Ig on NK cell function,preparation of the preservation fluid,and pathological diagnosis.Conclusions The professional level of organ transplantation in the armed forces had teken the foremost position in advance in the country.During the period of "12th Five-Year Plan" ,researches should be carried out on procurement,preservation and transplantation of the donated organs after cardiac death(DCD)organ.Meanwhile the foundational and clinical researches should be enhanced of immune tolerance,regulatory T lymphocyte,formulation of preservation fluid,and of animal experiment for closely bonding the foundational and clinical researches,and striving for greater research outcome.
ABSTRACT
To design and manufacture a new bone matrix material (NBM) composed of both organic and inorganic materials for bone tissue engineering, the osteogenic potential of NBM combined with osteoblasts was studied in vitro and in vivo. Osteoblasts from bone marrow stromal cells of New Zealand rabbit were cultured with NBM in vitro , then the materials combined with osteoblasts were implanted into the skeletal muscles of rabbits. The osteogenic potential of NBM was evaluated using contrast microscope, scan electromicroscope and histological examination. Osteoblasts could attach and proliferate well in the NBM, secrecting lots of extracellular matrix, while in vivo experiment of the NBM in osteoblasts group showed that a large number of lymphacytes and phagocytes invaded into the inner of the material in the rabbit skeletal muscle beds after 4 weeks of implantation, no new bone formation was observed after 8 weeks. The different osteogenic potential expressed by NBM between in vitro and in vivo may be due to the immunogenity of NBM which causes cellular immunoreaction to destroy the osteogenic environment. More attention should be paid to the immunoreaction problem in tissue engineering between the host and organic inorganic composite materials.
ABSTRACT
AIM:To investigate the effect of donor bone marrow derived dentritic cell (DC) treated with B7 - 1, B7 - 2 antisense oligonucleotide on mouse heart allografe survival time and its mechanism. METHODS: There were 7 groups of C57BL/10J (B10) mouse bone marrow DCs which were treated by 400 nM antisense oligonucleotide target to B7 -1, B7 -2 mRNA (AS B7- 1/2), B7- 1 mismatch oligo control ,B7- 2 mismatch control(mASB7- 1/2), lipofeetamine only and non-treatment, respectively. Each group of DC were named as ASB7- 1 DC, ASB7- 2 DC, mASB7 - 1 DC, mAS B7 - 2DC, and Lipo DC, respectively. RESULTS: Flow cytometer results shown that AS B7- 1/2 can inhibit B7- 1 (CD80)and B7- 2 (CD86) molecule express on DC surface, while control groups have no effects. To observe their tolerogenicity in mouse cardiac allograft model, B10→C3H heterotopic heart transplantation were performed. Recepients were received 2 x 106 of DC injection 7 days before transplantation. Results showed that both AS B7 - 1 DC and AS B7 - 2 DC can prolong mouse cardiac allograft survival time to (18.6 + 0.89) days and (23.67 + 10.73) days, respectively, compared with IL - 4 DC [ (6.22 + 0.97) days ( P < 0.01 ) ]. Two mismatch control groups can slightly prolong while oligo DC has no effect. For understanding its mechanism, each group of DC was used as stimulator to stimulated C3H spleen T cell. Results suggested that AS B7 - 1DC and AS B7 - 2 DC had less allo - stimulate function, including MLR and generation CTL and IL - 2 production than IL - 4 DC but control groups have no effect. CONCLUSION: Donor bone marrow derived DC treated with AS B7 - 1 oligo and AS B7 - 2 oligo expressed lower level of CD80 and CD86, respectively. These cells can induce allogeneic T cells anergy in vitro and markedly prolong mouse heart allograft survival time in vivo.