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Exosomes derived from mesenchymal stem cells (MSCs) play a similar role of stem cells in promoting healing and regeneration of tissue and organ through paracrine, which avoids the risks of direct transplantation of mesenchymal stem cells such as tumorigenic, ethics, immune rejection, et al. Exosomes derived from MSCs that are able to participate in intercellular communication, maintain homeostasis of microenvironment, promote cell proliferation and migration, repair extracellular matrix, and transmit between different species without causing obvious immune response, exhibiting great potential in healing and regeneration of tissue and organ. The authors review the characteristics, extraction and identification of exosomes derived from MSCs and their application in the repair and regeneration of spinal cord, skin, bone, tendons, nerves and other tissues, hoping to provide a reference for clinical application of exosomes derived from MSCs in tissue and organ repair.
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Esophageal cancer is one of the top ten of the world's most common cancer. Although the incidence of esophageal squamous cell carcinoma (ESCC) in some high-risk areas in East Asia has being decreasing, it is still the most common histologic subtypes. A great many of patients with ESCC not only are diagnosed in an advanced stage but also have a high mortality rate. With the application of tumor immunotherapy in ESCC treatment in recent years, the prognosis of ESCC patients has been improved to a certain extent. This article intends to review the research progress of immunotherapy in esophageal squamous cell carcinoma.
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The normal ventilatory function is severely impaired by tracheal traumas, stenoses, tumors and some congenital diseases, which could result in tissue hypoxia and endangering the life of the patient. Resection and reconstruction of tracheal lesions is the most effective way to treat these diseases. At present, there is still no long-term safe and reliable method to achieve the reconstruction of long-segment trachea injury in clinical practice, and tissue-engineered trachea may be the solution to this situation. Cartilage, as one of the most important parts of tissue engineered trachea, plays a key role in providing mechanical support and maintaining the integrity of trachea. Tracheal tissue engineering cartilage regeneration process consists of several important parts, including the source of the cartilage cells, tissue engineering scaffold construction strategy and hydrogel composite scaffold material preparation, and the affecting factors of biological activity and application. This article reviews the new strategies of tissue engineered tracheal cartilage regeneration and the existing obstacles in order to provide reference for clinical practice.
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At present, trachea reconstruction by tissue engineering technology of 3D bio-printing has become an ideal method for repairing long-segment trachea after injury, and how to select printing materials to manufacture appropriate tissue engineering trachea is the key to ensure the perfect survival of trachea grafts in the human body. Bioink is a cellular formula containing bioactive ingredients that could make or break the 3D printed tissue-engineered trachea. It is particularly important to find a bio-ink that has good biocompatibility and can print biological structures with high mechanical strength. This paper aims to review the advantages and disadvantages of bio-ink made of different materials, current application status and clinical application of 3D printed tissue-engineered trachea, so as to promote the clinical transformation of tissue-engineered trachea as soon as possible and put into practical clinical application systematically.
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@#The widespread use of low-dose computed tomography (LDCT) in lung cancer screening has enabled more and more lung nodules to get identified of which more than 20% are multiple pulmonary nodules. At present, there is no guideline or consensus for multiple pulmonary nodules whose management is based primarily on the pulmonary imaging characteristics and associated risk factors. Herein, this review covers the imaging methods, CT appearances and management of multiple pulmonary nodules.
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@#Objective To explore the independent risk factors for benign and malignant subsolid pulmonary nodules and establish a malignant probability prediction model. Methods A retrospective analysis was performed in 443 patients with subsolid pulmonary nodules admitted to Subei People's Hospital of Jiangsu Province from 2014 to 2018 with definite pathological findings. The patients were randomly divided into a modeling group and a validation group. There were 296 patients in the modeling group, including 125 males and 171 females, with an average age of 55.9±11.1 years. There were 147 patients in the verification group, including 68 males and 79 females, with an average age of 56.9±11.6 years. Univariate and multivariate analysis was used to screen the independent risk factors for benign and malignant lesions of subsolid pulmonary nodules, and then a prediction model was established. Based on the validation data, the model of this study was compared and validated with Mayo, VA, Brock and PKUPH models. Results Univariate and multivariate analysis showed that gender, consolidation/tumor ratio (CTR), boundary, spiculation, lobulation and carcinoembryonic antigen (CEA) were independent risk factors for the diagnosis of benign and malignant subsolid pulmonary nodules. The prediction model formula for malignant probability was: P=ex/(1+ex). X=0.018+(1.436× gender)+(2.068×CTR)+(−1.976×boundary)+ (2.082×spiculation)+(1.277×lobulation)+(2.296×CEA). In this study, the area under the curve was 0.856, the sensitivity was 81.6%, the specificity was 75.6%, the positive predictive value was 95.4%, and the negative predictive value was 39.8%. Compared with the traditional model, the predictive value of this model was significantly better than that of Mayo, VA, Brock and PKUPH models. Conclusion Compared with Mayo, VA, Brock and PKUPH models, the predictive value of the model is more ideal and has greater clinical application value, which can be used for early screening of subsolid nodules.
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Tissue engineering can provide alternatives to current methods for tracheal reconstruction. Functional and perfusable vascular network formation is critical to ensure the long-term survival and functionality of engineered tissues after their transplantation. The greatest challenges in tracheal replacement are restoration of blood supply rapidly to support cell metabolism and promote tissue healing and regeneration. The traditional methods of tracheal transplantation vascularization are traumatic and requires secondary operation, which don′t meet the current ethical requirements of rapid rehabilitation surgery. The integrated printing of cells, biomaterials and growth factors through 3D bio-printing technology is expected to become a new development direction of vascular tissue engineering trachea.
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Long tracheal lesions are mainly caused by stenosis, infection, trauma, malignant tumors and other factors. Resection of the diseased tissue or stenosis and end-to-end anastomosis is currently the gold standard for long tracheal lesions treatment. However, these treatment programs have proven to have major limitations. In recent years, tissue engineering technology has been regarded as a promising medical alternative treatment method, and the selection of scaffold materials is one of key parts. With the continuous exploration of domestic and foreign researchers, biological materials have been continuously developed and applied to the research of tissue engineering trachea. Tissue engineering degradable scaffold materials can be divided into natural polymer material scaffolds and synthetic polymer scaffolds according to the different sources. The scaffold material can be modified or compounded as needed to improve the biological properties of scaffolds. In addition, with the continuous development of biological printing technology, different scaffold materials can be better combined and used. Biodegradable scaffolds have become a new research direction in the field of tissue engineering trachea due to their polymer properties, and have good application prospects.
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Tissue engineering provides an effective treatment for tracheal reconstruction. The key to maintain airway function and ensure long-term survival of tracheal grafts is how to achieve epithelial cell regeneration, chondrocyte regeneration, and angiogenesis of the transplanted trachea. Growth factors are signaling molecules that direct cell development by providing biochemical cues for stem cell proliferation, migration, and differentiation. They play an important role in tissue engineering trachea regeneration. It is particularly important to design a delivery system that provides optimal activity, stability and adjustability for growth factors. This article summarizes the types, characteristics, functions of growth factors applied in the field of tissue engineering trachea, and the value of growth factors in tissue engineering trachea orthotopic transplantation aimed for promoting clinical transformation of tissue engineered trachea.
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The morbidity and mortality of lung cancer increase year by year, and it has become the main disease threatening life and health. Early stage lung cancer exists in the form of pulmonary nodules, asymptomatic growth, diagnosis has been in the middle and late stage. The formation of pulmonary nodules is a gradual process, and the cause of its pathogenesis is still unclear. Early diagnosis and early treatment of pulmonary nodules can significantly reduce lung cancer mortality. This article reviews the diagnostic value of clinical data, imaging examination and tumor markers in the evaluation of benign and malignant pulmonary nodules, and the early diagnosis model of benign and malignant pulmonary nodules, and discuss the research progress in the early diagnosis of benign and malignant pulmonary nodules.
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Objective:To investigate the biocompatible properties of tissue-engineered rabbit trachea treated by Triton-X 100 processed method (TPM) and detergent enzymatic method (DEM) with genipin cross-linking.Methods:TPM and DEM were used to decellularize New Zealand rabbit trachea, and then genipin was used for cross-linking. The mechanical properties of each tracheal sample were measured by universal tensile testing machine. The structure of the sample was observed by scanning electron microscope. The cytotoxicity of the sample was detected by cell contact toxicity assay. Fifteen healthy adult New Zealand rabbits with no specific pathogens were divided into the native tracheal transplantation group, the genipin cross-linked TPM acellular tracheal matrix transplantation group and the genipin cross-linked DEM acellular tracheal matrix transplantation group according to the random number table, 5 animals for each group. Animals in each group were sacrificed 30 days after transplantation, and graft samples were obtained. The microstructure was observed by hematoxylin-eosin staining and CD68 molecular immunohistochemical staining.Results:Biomechanical results showed that the mechanical properties of decellularized tracheas with genipin cross-linking were similar to native tracheas. The results of scanning electron microscopy showed that the matrix of cross-linked decellularized tracheas was more dense comparing with native tracheas, and the mesh-like ultrastructure formed on the outer surface of the genipin cross-linked DEM acellular tracheal matrix was conducive to cell adhesion. The results of cell contact toxicity results showed that the genipin cross-linked decellularized tracheas treated by DEM had better biocompatibility. The results of in vivo implantation and histological staining showed that genipin cross-linked DEM acellular tracheal matrix was less immunogenic comparing with genipin cross-linked TPM acellular tracheal matrix.Conclusions:Genipin can improve the ultrastructure of decellularized tracheal matrix without causing inflammatory. The genipin cross-linked decellularized tracheas treated by DEM has better biocompatibility and lower immunogenicity, which make it suitable for the replacement of tissue engineering trachea.
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Large or complete defect of trachea is a difficult problem in surgical reconstruction. Tracheal replacement therapy is an effective treatment. Due to the lack of ideal graft materials and poor survival after transplantation, tracheal clinical transplantation still faces enormous challenges. Systematic review clinical translation of circumferential tracheal substitutes. Four primary methodologies have emerged: tracheal allotransplantation, autologous tissue reconstruction, bioprosthetic reconstruction, and tissue engineered reconstruction. The main reason for the failure of current clinical graft are focused on that the lacks the mechanical properties of maintaining lumen patency, poor revascularization, and insufficient regeneration of epithelial cells and chondrocytes. The results show that laboratory work and animal experimental research on revascularization, re-epithelialization and further improvement of the mechanical properties of grafts are particularly important in order to promote the safer, more effective and widely used tissue engineering trachea for clinical diseases.
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Objective@#To explored the bio-compatibility and cartilage regeneration of the rabbits genipin cross-linked decellularized scaffold, to provide experimental and theoretical support for the clinical application of genipin cross-linked decellularized scaffold.@*Methods@#Detergent-enzyme method was used to prepare decellularized tracheal scaffolds. Cellular content of native trachea and decellularized trachea were compared by 4′, 6-diamidino-2-phenylindole(DAPI) staining. Masson trichrome staining was used to compare the histological structure of the progenitor tube, decellularized trachea, and genipin cross-linked decellularized trachea. Nine adult New Zealand white rabbits were randomly divided into autologous tracheal transplantation group (negative control group), allogeneic tracheal transplantation group (positive control group), and genipin cross-linked decellularized tracheal transplantation group (experimental group). Autologous bone marrow mesenchymal stem cells were implanted on the surface of trachea in each group. The blood cells and type II collagen were detected to compare the inflammatory response and chondrocyte regeneration after tracheal orthotopic transplantation in the three groups.@*Results@#After DAPI staining and light microscope observation (×200), the cell content of the acellular 7-cycle trachea [(143.0 ± 71.1) cells/field] was significantly lower than that of the native trachea [(853.5 ± 149.6) cells/field], and the difference was statistically significant (P<0.001). Masson′s trichrome staining showed that the tissue structure of genipin cross-linked decellularized trachea was more complete. Blood cell analysis and type II collagen test results showed that genipin cross-linked decellularized trachea transplanted with bone marrow mesenchymal stem cells after transplantation in situ has little rejection and can be converted into chondrocytes by the action of related growth factors in vivo.@*Conclusions@#Genipin cross-linked decellularized tracheal scaffold combined with stem cell transplantation can successfully construct a tracheal in situ replacement model. This study provides a strong support for the research of tissue engineering trachea.
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Esophageal cancer is one of the malignant tumors with the highest morbidity and mortality in China. Its early clinical symptoms are not typical, and the patients are already in the middle and late stage when they go to see the doctor. The 5-year survival rate of these patients is low and the prognosis is poor. At present, the precision medicine is gradually being applied to the field of clinical oncology. The detection of circulating tumor cells (CTC) has the advantages of non-invasive, easy to obtain specimens, reflect the overall state of the tumor, real-time monitoring, etc. The CTC detection has gradually become a hot research direction. CTC is tumor cell detached from the primary or metastatic tumors and released into the peripheral blood circulation. CTC detection can dynamically reflect the status of tumors. Combined with the latest reports at home and abroad, this paper mainly reviews the application and limitations of CTC in the field of esophageal cancer.
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With the development of precision medicine in the field of tumor,thanks to the latest screening technology,the demand for real-time monitoring of tumor is increasingly high.Traditional tissue biopsy is not suitable for repeated due to clinical problems such as puncture clinical risk and tumor heterogeneity.Ultrasound,endoscopy and other imaging examinations are highly subjective,and it is difficult to detect small lesions,and increasingly unable to meet the requirements of real-time monitoring.However,circulating tumor DNA,with its advantages of simple sample acquisition,small trauma,repeatability and real-time monitoring efficacy,has an important application prospect in tumor diagnosis and treatment.Based on the latest reports at home and abroad,this paper reviews the research progress of circulating tumor DNA in the early diagnosis,treatment and prognosis of esophageal cancer.
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Tissue engineering is a comprehensive discipline that combines materials science, life sciences, and engineering to repair, and improve and preserve damaged tissues or organs through cell or tissue reconstruction. In recent years, with the rapid development of tissue engineering technology, tissue engineering trachea has gradually become a new approach to tracheal replacement therapy. However, due to the slender and periodic distribution of the blood vessels supplying the trachea, tracheal grafts cannot obtain sufficient blood supply to maintain its demand, making its vascularization problem one of the major obstacles to the development of tissue engineering trachea. In the construction of tissue engineering trachea, the vascularization strategy of seed cells, tracheal scaffold and growth factors have gradually become the focus of research. In this paper, the current researches on tissue engineering tracheal vascularization were reviewed.
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Objective To prepare 3D printed porous tracheal graft fabricated by PCL and to select the appropriate pore size and surface modification techniques,in order to explore its effect on cell behavior.Methods The PCL porous tracheal graft was prepared by 3D printing technology and biomechanical properties of the graft were measured by means of longitudinal tension,radial compression and three-point bending test.The porous grafts were surface-modified through hydrolysis,amination and nanocrystallization treatment and then characterized by energy dispersive spectroscopy(EDS).The effect of different pore sizes and surface modifications on the cell proliferation behavior was evaluated by CCK-8 and scanning electron microscopy (SEM).Results The 3 D printed porous tracheal graft had similar morphology with the native tracheas(P ＞ 0.05) and better biomechanical properties(P ＜0.05).It was more suitable for cell adhesion and proliferation when the pore size is 200 μm (P ＜ 0.05).Compared to hydrolysis and amination,nanocrystallization treatment successfully improved the cytotropism of the 3D printed tracheal graft(P ＜ 0.05).Conclusion 3 D printed porous tracheal graft shows favorable biomechanical properties.The appropriate pore size of the 3D printed porous tracheal graft is 200 μm and the appropriate surface modification techniques is nanocrystallization.
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Tissue engineering has already become an important research direction of trachea substitute; the construction of the scaffold is one of the key factors for a tissue engineering trachea .With the development and the maturity of the technology of 3D-printing, the design and manufacture of the tissue engineered scaffold is widely broadened, various types of 3D-printed scaffold are researched constantly.This review aims to summarize and evaluates the latest progress of the experiments about 3D-printed tissue engineering scaffold.
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BACKGROUND: Different decellularization methods can affect the integrity and the biomechanical and biocompatible properties of the tracheal matrix. Natural cross-linking with genipin can be applied to improve those properties. The goals of this study were to evaluate the effects of different decellularization methods on the properties of genipin-cross-linked decellularized tracheal matrices in rabbits. METHODS: The tracheas of New Zealand rabbits were decellularized by the Triton-X 100-processed method (TPM) and the detergent-enzymatic method (DEM) and were then cross-linked with genipin. Mechanical tests, haematoxylin-eosin staining, Masson trichrome staining, Safranin O staining, DAPI staining, scanning electronic microscopy (SEM), and biocompatibility tests were used to evaluate the treatment. The bioengineered trachea and control trachea were then implanted into allogeneic rabbits for 30 days. The structural and functional analyses were performed after transplantation. RESULTS: The biomechanical tests demonstrated that the biomechanical properties of the decellularized tracheas decreased and that genipin improved them (p < 0.05). The histological staining results revealed that most of the mucosal epithelial cells were removed and that the decellularized trachea had lower immunogenicity than the control group. The analysis of SEM revealed that the decellularized trachea retained the micro- and ultra-structural architectures of the trachea and that the matrices cross-linked with genipin were denser. The biocompatibility evaluation and in vivo implantation experiments showed that the decellularized trachea treated with the DEM had better biocompatibility than that treated with the TPM and that immunogenicity in the cross-linked tissues was lower than that in the uncross-linked tissues (p < 0.05). CONCLUSION: Compared with the trachea treated with the TPM, the rabbit trachea processed by the DEM had better biocompatibility and lower immunogenicity, and its structural and mechanical characteristics were effectively improved after the genipin treatment, which is suitable for engineering replacement tracheal tissue.
Subject(s)
Rabbits , Epithelial Cells , Methods , Microscopy , Tissue Engineering , TracheaABSTRACT
Objective To explored the bio-compatibility and cartilage regeneration of the rabbits genipin cross-linked decellularized scaffold, to provide experimental and theoretical support for the clinical application of genipin cross-linked decellularized scaffold. Methods Detergent-enzyme method was used to prepare decellularized tracheal scaffolds. Cellular content of native trachea and decellularized trachea were compared by 4', 6-diamidino-2-phenylindole(DAPI) staining. Masson trichrome staining was used to compare the histological structure of the progenitor tube, decellularized trachea, and genipin cross-linked decellularized trachea. Nine adult New Zealand white rabbits were randomly divided into autologous tracheal transplantation group (negative control group), allogeneic tracheal transplantation group (positive control group), and genipin cross-linked decellularized tracheal transplantation group (experimental group). Autologous bone marrow mesenchymal stem cells were implanted on the surface of trachea in each group. The blood cells and type II collagen were detected to compare the inflammatory response and chondrocyte regeneration after tracheal orthotopic transplantation in the three groups. Results After DAPI staining and light microscope observation (×200), the cell content of the acellular 7-cycle trachea [(143.0 ± 71.1) cells/field] was significantly lower than that of the native trachea [(853.5 ± 149.6) cells/ field], and the difference was statistically significant (P<0.001). Masson's trichrome staining showed that the tissue structure of genipin cross -linked decellularized trachea was more complete. Blood cell analysis and type II collagen test results showed that genipin cross-linked decellularized trachea transplanted with bone marrow mesenchymal stem cells after transplantation in situ has little rejection and can be converted into chondrocytes by the action of related growth factors in vivo. Conclusions Genipin cross-linked decellularized tracheal scaffold combined with stem cell transplantation can successfully construct a tracheal in situ replacement model. This study provides a strong support for the research of tissue engineering trachea.