AIM To determine the influence of the construction design over the biological component's performance in an experimental bio-artificial liver(BAL) device.METHODS Two BAL models for liver microorgans(LMOs) were con...AIM To determine the influence of the construction design over the biological component's performance in an experimental bio-artificial liver(BAL) device.METHODS Two BAL models for liver microorgans(LMOs) were constructed. First, we constructed a cylindrical BAL and tested it without the biological component to establish its correct functioning. Samples of blood and biological compartment(BC) fluid were taken after 0, 60, and 120 min of perfusion. Osmolality, hematocrit, ammonia and glucose concentrations, lactate dehydrogenase(LDH) release(as a LMO viability parameter), and oxygen consumption and ammonia metabolizing capacity(as LMO functionality parameters) were determined. CPSI and OTC gene expression and function were measured. The second BAL, a "flat bottom" model, was constructed using a 25 cm2 culture flask while maintaining all other components between the models. The BC of both BALs had the same capacity(approximately 50 cm3) and both were manipulated with the same perfusion system. The performances of the two BALs were compared to show the influence of architecture.RESULTS The cylindrical BAL showed a good exchange of fluids and metabolites between blood and the BC, reflected by the matching of osmolalities, and glucose and ammonia concentration ratios after 120 min of perfusion. No hemoconcentration was detected, the hematocrit levels remained stable during the whole study, and the minimal percentage of hemolysis(0.65% ± 0.10%) observed was due to the action of the peristaltic pump. When LMOs were used as biological component of this BAL they showed similar values to the ones obtained in a Normothermic Reoxygenation System(NRS) for almost all the parameters assayed. After 120 min, the results obtained were: LDH release(%): 14.7 ± 3.1 in the BAL and 15.5 ± 3.2 in the NRS(n = 6); oxygen consumption(μmol/min?g wet tissue): 1.16 ± 0.21 in the BAL and 0.84 ± 0.15 in the NRS(n = 6); relative expression of Cps1 and Otc: 0.63 ± 0.12 and 0.67 ± 0.20, respectively, in the BAL, and 0.86 ± 0.10 and 0.82 ± 0.07, respectively, in the NRS(n = 3); enzymatic activity of CPSI and OTC(U/g wet tissue): 3.03 ± 0.86 and 222.0 ± 23.5, respectively, in the BAL, and 3.12 ± 0.73 and 228.8 ± 32.8, respectively, in the NRS(n = 3). In spite of these similarities, LMOs as a biological component of the cylindrical BAL were not able to detoxify ammonia at a significant level(not detected vs 35.1% ± 7.0% of the initial 1 mM NH4+ dose in NRS, n = 6). Therefore, we built a second BAL with an entirely different design that offers a flat base BC. When LMOs were placed in this "flat bottom"device they were able to detoxify 49.3% ± 8.8% of the initial ammonia overload after 120 min of perfusion(n = 6), with a detoxification capacity of 13.2 ± 2.2 μmol/g wet tissue.CONCLUSION In this work, we demonstrate the importance of adapting the BAL architecture to the biological component characteristics to obtain an adequate BAL performance.展开更多
Islet transplantation could become an ideal treatment for severe diabetes to prevent hypoglycemia shock and irreversible diabetic complications, once some of the major and unresolved obstacles are overcome, including ...Islet transplantation could become an ideal treatment for severe diabetes to prevent hypoglycemia shock and irreversible diabetic complications, once some of the major and unresolved obstacles are overcome, including limited donor supplies and side effects caused by permanent immunosuppressant use. Approximately 30 years ago, some groups succeeded in improving the blood glucose of diabetic animals by transplanting encapsulated islets with semi-permeable membranes consisting of polymer. A semi-permeable membrane protects both the inner islets from mechanical stress and the recipient’s immune system (both cellular and humoral immunities), while allowing bidirectional diffusion of nutrients, oxygen, glucose, hormones and wastes, i.e., immune-isolation. This device, which enables immune-isolation, is called encapsulated islets or bio-artificial pancreas. Encapsulation with a semipermeable membrane can provide some advantages: (1) this device protects transplanted cells from the recipient’s immunity even if the xenogeneic islets (from large animals such as pig) or insulin-producing cells are derived from cells that have the potential for differentiation (some kinds of stem cells). In other words, the encapsulation technique can resolve the problem of limited donor supplies; and (2) encapsulation can reduce or prevent chronic administration of immunosuppressants and, therefore, important side effects otherwise induced by immunosuppressants. And now, many novel encapsulated islet systems have been developed and are being prepared for testing in a clinical setting.展开更多
At present, proven clinical treatments but no cures are available for diabetes, a global epidemic with a huge economic burden. Transplantation of islets ofLangerhans by their infusion into vascularized organs is an ex...At present, proven clinical treatments but no cures are available for diabetes, a global epidemic with a huge economic burden. Transplantation of islets ofLangerhans by their infusion into vascularized organs is an experimental clinical protocol, the first approach to attain cure. However, it is associated with lifelong use of immunosuppressants. To overcome the need for immunosuppression, islets are encapsulated and separated from the host immune system by a permselective membrane. The lead material for this application is alginate which was tested in many animal models and a few clinical trials. This review discusses all aspects related to the function of transplanted encapsulated islets such as the basic requirements from a permselective membrane(e.g., allowable hydrodynamic radii, implications of the thickness of the membrane and relative electrical charge). Another aspect involves adequate oxygen supply, which is essential for survival/performance of transplanted islets, especially when using large retrievable macrocapsules implanted in poorly oxygenated sites like the subcutis. Notably, islets can survive under low oxygen tension and are physiologically active at > 40 Torr. Surprisingly, when densely crowded, islets are fully functional under hyperoxic pressure of up to 500 Torr(> 300% of atmospheric oxygen tension). The review also addresses an additional category of requirements for optimal performance of transplanted islets, named auxiliary technologies. These include control of inflammation, apoptosis, angiogenesis, and the intra-capsular environment. The review highlights that curing diabetes with a functional bio-artificial pancreas requires optimizing all of these aspects, and that significant advances have already been made in many of them.展开更多
Continuous jumping behavior,a kind of endurance locomotion,plays important roles in insect ecological adaption and survival.However,the methods used for the efficient evaluation of insect jumping behavior remain large...Continuous jumping behavior,a kind of endurance locomotion,plays important roles in insect ecological adaption and survival.However,the methods used for the efficient evaluation of insect jumping behavior remain largely lacking.Here,we developed a locomotion detection system named JumpDetector with automatic trajectory tracking and data analysis to evaluate the jumping of insects.This automated system exhibits more accurate,efficient,and adjustable performance than manual methods.By using this automatic system,we characterized a gradually declining pattern of continuous jumping behavior in 4th‐instar nymphs of the migratory locust.We found that locusts in their gregarious phase outperformed locusts in their solitary phase in the endurance jumping locomotion.Therefore,the JumpDetector could be widely used in jumping behavior and endurance locomotion measurement.展开更多
基金Supported by Universidad Nacional de Rosario(UNR),BIO 272,Resol.C.S.,No.677/2013Agencia Nacional de Promoción Científica y Tecnológica(ANPCyT),PICT-03-14492,BID 1728 OC/AR(Argentina)a grant from Regione Autonoma FriuliVenezia Giulia,Italy
文摘AIM To determine the influence of the construction design over the biological component's performance in an experimental bio-artificial liver(BAL) device.METHODS Two BAL models for liver microorgans(LMOs) were constructed. First, we constructed a cylindrical BAL and tested it without the biological component to establish its correct functioning. Samples of blood and biological compartment(BC) fluid were taken after 0, 60, and 120 min of perfusion. Osmolality, hematocrit, ammonia and glucose concentrations, lactate dehydrogenase(LDH) release(as a LMO viability parameter), and oxygen consumption and ammonia metabolizing capacity(as LMO functionality parameters) were determined. CPSI and OTC gene expression and function were measured. The second BAL, a "flat bottom" model, was constructed using a 25 cm2 culture flask while maintaining all other components between the models. The BC of both BALs had the same capacity(approximately 50 cm3) and both were manipulated with the same perfusion system. The performances of the two BALs were compared to show the influence of architecture.RESULTS The cylindrical BAL showed a good exchange of fluids and metabolites between blood and the BC, reflected by the matching of osmolalities, and glucose and ammonia concentration ratios after 120 min of perfusion. No hemoconcentration was detected, the hematocrit levels remained stable during the whole study, and the minimal percentage of hemolysis(0.65% ± 0.10%) observed was due to the action of the peristaltic pump. When LMOs were used as biological component of this BAL they showed similar values to the ones obtained in a Normothermic Reoxygenation System(NRS) for almost all the parameters assayed. After 120 min, the results obtained were: LDH release(%): 14.7 ± 3.1 in the BAL and 15.5 ± 3.2 in the NRS(n = 6); oxygen consumption(μmol/min?g wet tissue): 1.16 ± 0.21 in the BAL and 0.84 ± 0.15 in the NRS(n = 6); relative expression of Cps1 and Otc: 0.63 ± 0.12 and 0.67 ± 0.20, respectively, in the BAL, and 0.86 ± 0.10 and 0.82 ± 0.07, respectively, in the NRS(n = 3); enzymatic activity of CPSI and OTC(U/g wet tissue): 3.03 ± 0.86 and 222.0 ± 23.5, respectively, in the BAL, and 3.12 ± 0.73 and 228.8 ± 32.8, respectively, in the NRS(n = 3). In spite of these similarities, LMOs as a biological component of the cylindrical BAL were not able to detoxify ammonia at a significant level(not detected vs 35.1% ± 7.0% of the initial 1 mM NH4+ dose in NRS, n = 6). Therefore, we built a second BAL with an entirely different design that offers a flat base BC. When LMOs were placed in this "flat bottom"device they were able to detoxify 49.3% ± 8.8% of the initial ammonia overload after 120 min of perfusion(n = 6), with a detoxification capacity of 13.2 ± 2.2 μmol/g wet tissue.CONCLUSION In this work, we demonstrate the importance of adapting the BAL architecture to the biological component characteristics to obtain an adequate BAL performance.
基金Supported by Research Seeds Quest Program in Japan Science and Technology Agency (NS)the Uehara Memorial Foundation (NS)Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports Science and Technology of Japan, B: 22390253 (SE), C: 22591513 (NS)
文摘Islet transplantation could become an ideal treatment for severe diabetes to prevent hypoglycemia shock and irreversible diabetic complications, once some of the major and unresolved obstacles are overcome, including limited donor supplies and side effects caused by permanent immunosuppressant use. Approximately 30 years ago, some groups succeeded in improving the blood glucose of diabetic animals by transplanting encapsulated islets with semi-permeable membranes consisting of polymer. A semi-permeable membrane protects both the inner islets from mechanical stress and the recipient’s immune system (both cellular and humoral immunities), while allowing bidirectional diffusion of nutrients, oxygen, glucose, hormones and wastes, i.e., immune-isolation. This device, which enables immune-isolation, is called encapsulated islets or bio-artificial pancreas. Encapsulation with a semipermeable membrane can provide some advantages: (1) this device protects transplanted cells from the recipient’s immunity even if the xenogeneic islets (from large animals such as pig) or insulin-producing cells are derived from cells that have the potential for differentiation (some kinds of stem cells). In other words, the encapsulation technique can resolve the problem of limited donor supplies; and (2) encapsulation can reduce or prevent chronic administration of immunosuppressants and, therefore, important side effects otherwise induced by immunosuppressants. And now, many novel encapsulated islet systems have been developed and are being prepared for testing in a clinical setting.
文摘At present, proven clinical treatments but no cures are available for diabetes, a global epidemic with a huge economic burden. Transplantation of islets ofLangerhans by their infusion into vascularized organs is an experimental clinical protocol, the first approach to attain cure. However, it is associated with lifelong use of immunosuppressants. To overcome the need for immunosuppression, islets are encapsulated and separated from the host immune system by a permselective membrane. The lead material for this application is alginate which was tested in many animal models and a few clinical trials. This review discusses all aspects related to the function of transplanted encapsulated islets such as the basic requirements from a permselective membrane(e.g., allowable hydrodynamic radii, implications of the thickness of the membrane and relative electrical charge). Another aspect involves adequate oxygen supply, which is essential for survival/performance of transplanted islets, especially when using large retrievable macrocapsules implanted in poorly oxygenated sites like the subcutis. Notably, islets can survive under low oxygen tension and are physiologically active at > 40 Torr. Surprisingly, when densely crowded, islets are fully functional under hyperoxic pressure of up to 500 Torr(> 300% of atmospheric oxygen tension). The review also addresses an additional category of requirements for optimal performance of transplanted islets, named auxiliary technologies. These include control of inflammation, apoptosis, angiogenesis, and the intra-capsular environment. The review highlights that curing diabetes with a functional bio-artificial pancreas requires optimizing all of these aspects, and that significant advances have already been made in many of them.
基金This work was supported by the National Natural Science Foundation of China(Grant No.31772531 and 31601875)the Strategic Priority Program of CAS(Grant No.XDB11010000).
文摘Continuous jumping behavior,a kind of endurance locomotion,plays important roles in insect ecological adaption and survival.However,the methods used for the efficient evaluation of insect jumping behavior remain largely lacking.Here,we developed a locomotion detection system named JumpDetector with automatic trajectory tracking and data analysis to evaluate the jumping of insects.This automated system exhibits more accurate,efficient,and adjustable performance than manual methods.By using this automatic system,we characterized a gradually declining pattern of continuous jumping behavior in 4th‐instar nymphs of the migratory locust.We found that locusts in their gregarious phase outperformed locusts in their solitary phase in the endurance jumping locomotion.Therefore,the JumpDetector could be widely used in jumping behavior and endurance locomotion measurement.
