46 results about "Liver support systems" patented technology

The present invention provides a preparing method of a human hepatic progenitor cell which is amplified and cultivated in vitro, including: a. separating the human hepatic progenitor cell; b. co-cultivating a feeder cell and the human hepatic progenitor cell separated from the step a by a medium having no serum on an extracellular matrix containing human fibrin sealant or other analogues, obtaining a human hepatic progenitor cell colony by amplification. The human hepatic progenitor cell colony is easy to separate from the surface of human fibrin sealant by the simple gelatinolytic band process, purified or / and subcultured by further single cell preparation technology process such as enzymatic degradation etc. The human hepatic progenitor cell prepared by the method is hepatic progenitor cell treatment, including a cell transplantation and a bioartificial liver support system, providing excellent human hepatocyte source for cytotoxicity test platform in the drug screening, virus infection and drug screening platform etc.

The invention provides a cell reactor and an artificial liver support system comprising the same. The cell reactor comprises a container, a liquid outlet is formed at the bottom of the container, a sealing cover is arranged at the top of the container, a liquid inlet is formed on the sealing cover, layers of filter meshes of 100-400 meshes are respectively arranged at the bottom of the container and in the sealing cover at the top of the container, covers which are in seal fit with the liquid outlet and the inlet are formed at the liquid outlet and the inlet, and a mixture of a micro-carrier growing liver cells and resin is accommodated between the two layers of the filter meshes in the container. The reactor is connected on a dialysate circulation path of a blood purifying device for constituting the artificial liver support system, thereby leading the liver cells not to be in direct contact with blood and realizing good biological safety; furthermore, the reactor can be used for a plurality of times through regeneration treatment, thereby greatly reducing the treatment cost of a biological artificial liver.

The invention discloses a dual-cavity liquid storage tank for a biological artificial liver support system. The dual-cavity liquid storage tank comprises an inner cavity and an outer cavity, wherein the top of the outer cavity is provided with a first liquid inlet and a first air pressure balance hole; the top of the inner cavity is provided with a second liquid inlet and a second air pressure balance hole; the bottom of the inner cavity is provided with a first liquid outlet; the side wall, which is close to the bottom, of the inner cavity is provided with a second liquid outlet; the second liquid outlet passes through the outer cavity by means of a pipelike passage, and directly leads to the outside of the dual-cavity liquid storage tank from the inner cavity; and the pipelike passage is provided with a plurality of outer cavity side holes on the partial side wall of the outer cavity. The dual-cavity liquid storage tank for the biological artificial liver support system realizes that severe hepatitis plasma flows through a bioreactor for multiple times to form a high-efficiency circulation path, thereby playing better therapeutic effect. The proportion of volume sizes of the inner cavity and the outer cavity of the dual-cavity liquid storage tank for the biological artificial liver support system can also be reset according to clinical concrete practical requirements, and is expanded or reduced so as to be applied to clinic treatment more reasonably.

An artificial, extracorporeal system for liver replacement and / or assistance, comprises a liver dialysis device for conducting hemodialysis on a patient suffering from liver failure. The liver dialysis device comprises a first standard hollow fiber membrane dialyzer which does not allow passage of an essential amount of albumin over the membrane wall and which is perfused with the patient's blood, and a second hollow fiber membrane dialyzer which allows the passage of essential but defined amounts of albumin over the membrane wall and which receives the blood of the first standard hemodialyzer. The filtrate space is closed off from the lumen space of the hollow fibers and is populated by adsorbent material which may comprise one or more different adsorbents.

The invention discloses an immortalized human liver cell line, a preparation method and an application thereof. The immortalized human liver cell line has the main function of primarily cultured humanliver cell. The preparation method comprises the following steps of: transferring SV40T antigen and human telomerase catalyzed subunit gene into primarily cultured separated human normal liver cell by slow virus carrier; and sieving in a cloning way to obtain the immortalized human liver cell line. The immortalized human liver cell line also can be extrinsically amplified in large scales in a microcarrier way. The immortalized human liver cell line can be used for preparing a biological artificial liver support system and preparing the medicament for curing the liver failure.

The invention discloses an artificial liver reactor. The artificial liver reactor comprises an input header pipe, an output header pipe, and one or more cell culture bottles connected in parallel or in series, wherein the cell culture bottles are connected between the input header pipe and the output header pipe, an input pipe and an output pipe are arranged at two sides of the bottom of each cell culture bottle, and a peristaltic pump is arranged on each input pipe; a separation net is arranged in each cell culture bottle, the part between the separation net and the bottom of each cell culture bottle is filled with a filler with an adsorption function, a flake-shaped carrier is loaded to each separation net, and hepatic cells attach to the flake-shaped carriers. For the artificial liver reactor, due to the arrangement of the peristaltic pumps and the flake-shaped carriers, the cell loading capacity, the effective exchange area and the metabolism exchange efficiency of the artificial liver reactor can be effectively improved. The invention further discloses a method for preparing the artificial liver reactor, and a circular pouring bioartificial liver support system comprising the artificial liver reactor.

The invention discloses a construction method of a three-dimensional liver microtissue unit for a bio-artificial liver support system. The construction method is characterized by comprising the steps that decellularized scaffold components of a pig liver are encapsulated by microcapsules prepared from sodium alginate-polycations, liver cells, vascular endothelial cells and fibroblasts are composited, and the functional three-dimensional liver microtissue unit is constructed through cell self-assembly and applied to the bio-artificial liver support system. According to the method, operation is easy, cost is low, the liver cells, the vascular endothelial cells and the fibroblasts are self-assembled into three-dimensional liver microtissue by simulating interaction between the cells and an extracellular matrix, interaction between the cells and soluble factors and interaction between the cells and the cells in a liver tissue microenvironment, the three-dimensional liver microtissue has good synthesis, secretion and detoxification functions, and therefore the three-dimensional liver microtissue can serve as the microunit to be applied to the bio-artificial liver support system.

An extracorporeal system for liver dialysis comprises a filter device having hollow fibers with integrated ion-exchange particles and hydrophobic adsorbent particles in the filtrate space. The system can be used for the treatment of acute liver failure and acute-on-chronic liver failure.

The invention relates to medical facilities, aiming at providing a hybrid artificial liver support system equipped with a nano fibre sheet stacked reactor. The system comprises a plasma separating part, a nonbiological liver circulating part and a biological liver circulating part which comprises a thermostatic gas bath incubator; an extracorporeal circulating pool, a plasma pump and dissolved oxygen which are connected sequeitically and form a circulating system; a temperature testing bottle; and the nano fibre sheet stacked reactor. The system is easily to be amplified so as to improve the defect that cells block a semipermeable membrane easily, the efficiency of material exchange is high and both oxygenation and immunity obstruction function are provided. The reactor has strong function, can be used for biological or hybrid artificial liver, and also used for the cultivation and inducing differentiation of stem cells. The reactor of the system has oxygenation function, thereby saving an oxygenator needing to be equipped independently in normal systems.

The invention provides a novel serum free medium and a preparation method and application of the medium. The serum free medium overcomes defects of the traditional serum media, and is obviously superior to serum free media reported in the conventional documents, improves the possibility of supporting systematical treatment clinical application through cell transplantation, tissue engineering liver and bioartificial liver, and has high practical value.

The invention relates to an extracorporeal circulation tank of an artificial liver supporting system, which consists of a circulatory part and a control part. The circulatory part is provided with a tank body, an inlet, a hollow fiber pipe, an outlet, a three-way pipe, an outlet of the circulation tank, and a feedback inlet; and the control part is provided with the tank body, an oxygen inlet, an opening, a warming device, a fan, a control pipeline, a display screen and a plastic tube. The hollow fiber pipe is embedded on the inner wall of the tank body, the inlet and the outlet are arranged corresponding to two ends of the hollow fiber pipe, one end of the three-way pipe is connected with an outlet and the other two ends are connected with a peristaltic pump and the outlet of the circulation tank respectively, the upper part of the tank body is provided with the oxygen inlet and the lower part is provided with the opening, and the display screen is arranged on the upper part of the tank body and is connected with the control pipeline. Compared with the prior extracorporeal circulation device, the extracorporeal circulation tank has the function of monitoring temperature, pump speed and blood oxygen content in real time, can realize recirculation for the blood plasma in a reactor, guides the substance exchange between hepatocyte and severe liver blood plasma to be more complete, and improves the efficiency of an artificial liver device. The extracorporeal circulation tank has the advantages of reasonable design, convenient operation and practicality.

The invention relates to a bioartificial liver supporting system which comprises a blood circulation system, a plasmapheresis circulation system and a hepatocyte microsphere circulation system. An integrated blood oxygen, pH, blood pressure and temperature sensor is adopted for not only monitoring various physiological parameters in the system in real time, but also reducing the complication degree of the whole system, and facilitating data management; furthermore, a hepatocyte microsphere culture fluid storage device and a recycling method are adopted, so that not only can nutrient substances and the oxygen transmitting capacity be improved and can durable functions and activity of hepatocytes be maintained, but also full contact between the hepatocyte and plasma is facilitated, the bioartificial liver supporting system is capable of substituting the liver function of a patient with hepatic failure in a long time; furthermore, the hepatocyte microsphere culture fluid storage device is provided with a culture fluid extraction port and a culture fluid adding port, so that under the condition of not influencing normal operation of the system, cell samples can be extracted, the cell activity is detected and a fresh culture fluid containing hepatocyte microspheres is added.

The invention provides preparation of an animal model for screening hepatocyte growth-promoting regenerative medicines in fulminant liver function failure curing process and evaluating therapeutic effect of a tissue engineering liver supporting system or hepatic cell and stem cell transplantation by using amanitin and endotoxin lipopoly-saccharide, wherein an application method adopts single intraperitoneal instillation with dosage of 0.1mg / kg, and the dosage of the endotoxin is 1mug / kg. The invention further provides a method for preparing fulminant liver function failure and a fulminant liver function failure animal model prepared by the method. The animal model can be used for evaluation of biotechnological new drugs that a rodent animal model cannot accomplish, and can be used for the evaluation of tissue engineering liver, biological artificial liver, the hepatic cell and stem cell transplantation treatment technologies.

The invention discloses a membrane type platy biological artificial liver reactor. The reactor comprises a tank, and a multilayer cell culture unit and a central cell suspension injection tube which are arranged in the tank, wherein in the multilayer cell culture unit, a cell culture membrane is circularly horizontally arranged, a scaffold is spoke-shaped or screen-shaped and has a central hole, the cell culture membrane is arranged on the upper side, and the scaffold is arranged on the lower side; the total height of the multilayer unit is about 2 / 3 of a cylindrical part of the tank. According to the membrane type platy biological artificial liver reactor designed in the invention, the cell culture membrane is horizontally favorable for liver cell adherence, a flow direction of plasma isperpendicular to the cell culture membrane, the cells difficultly drop, and the plasma and the cells can be fully contacted and can perform exchange of substances; due to the cell suspension injectionamount, the occupancy of membrane cells on each layer can be controlled, the plasma permeability is ensured, enough liver cells can be obtained by virtue of a multilayer plate structure, and a bioreactor in the conventional artificial liver support system is replaced.

The invention discloses a combined bioartificial liver supporting system. The supporting system at least comprises branch pipelines connected in order, the branch pipelines are a blood input branch pipeline of which an upstream tail end is arranged to be a blood input end, a first slurry separating branch pipeline at least including a first plasma separator, a non- biological cleaning branch pipeline at least including a plasma hemoperfusion apparatus and a bilirubin absorber, a biological cleaning branch pipeline at least including a liver cell culture tank component, a plasma returning branch pipeline of which downstream tail end is arranged to be a blood output end; tee devices are connected among the first plasma separating branch pipeline, the biological cleaning branch pipeline and the non-biological cleaning branch pipeline, between the outlet end of the non-biological cleaning branch pipeline and the biological cleaning branch pipeline, and between an outlet end of the non-biological cleaning branch pipeline and the plasma returning branch pipeline; the tee devices comprise tee joints and branch paths connected with the tee joints; at least two branch paths are provided with current limiting pieces and connection pieces.

The invention provides a novel serum free medium and a preparation method and application of the medium. The serum free medium overcomes defects of the traditional serum media, and is obviously superior to serum free media reported in the conventional documents, improves the possibility of supporting systematical treatment clinical application through cell transplantation, tissue engineering liver and bioartificial liver, and has high practical value.

The invention discloses a bioartificial liver support system and a combined type liquid storage tank thereof, wherein the combined type liquid storage tank comprises a closed liquid inlet tank and a closed liquid return tank; the top of the liquid inlet tank is provided with a first liquid inlet and a first air pressure balancing hole; the bottom of the liquid inlet tank is provided with a first liquid outlet and a second liquid inlet; the top of the liquid return tank is provided with a third liquid inlet and a second air pressure balancing hole; the bottom of the liquid return tank is provided with a second liquid outlet and a third liquid outlet; and the second liquid outlet is communicated with the second liquid inlet by a first communicating pipe which is provided with a direction and flow control device. The invention can improve material interchange efficiency between hepatic failure blood plasma and a bioreactor, avoids futile cycle, does not need to depend on the chimney effect of pumps, has simple structure and stable operation and has improvement of the bioartificial liver support system. In the invention, volume of the liquid inlet tank and the liquid return tank can be adjusted according to specific requirements to suit clinical application.

An extracorporeal system for liver dialysis comprises a filter device having hollow fibers with integrated ion-exchange particles and hydrophobic adsorbent particles in the filtrate space. The system can be used for the treatment of acute liver failure and acute-on-chronic liver failure.

Disclosed herein are bioartificial liver systems (“BAL” or “liver assist device”) that employ liver organoids. The disclosed systems may be used to provide a therapeutic benefit to an individual in need thereof, particularly an individual having compromised liver function. The systems may include an in vivo or ex vivo component, wherein a liver function is provided to the individual using the disclosed systems.

The invention relates to a medical equipment and aims at providing a hybrid artificial liver supporting system equipped with a perforated brick type filling bracket type reactor. The system comprises a plasma separating part, a non-biological liver circulating part and a biological liver circulating part; the biological liver circulating part comprises a constant temperature air bath incubator which plays the role of heat preservation and an extracorporeal circulation pool, a plasma pump, a dissolved oxygen and temperature testing bottle and the perforated brick type filling bracket type reactor which are connected into a circulation system in sequence. The invention not only solves the problem that the bracket type reactor is lack of immune isolation and is insufficient for oxygen supply,but also makes up the defects that the hollow fiber type reactor has insufficient cell growing space and poor cell adhesion, is lack of three-dimensional growing environment and is easy to block semi-permeable membranes. The invention integrates the functions of oxygenation, immune isolation, three-dimensional culture and the like and has strong comprehensive performance, simple manufacturing technique, low cost and easy amplification. As the reactor of the system has the function of oxygenation, the system saves an oxygenator which generally needs to be equipped independently.

The present disclosure relates to an artificial, extracorporeal system for supporting the function of the liver of a patient suffering from liver failure, which is characterized in that it comprises a first high-flux or high cut-off hollow fiber membrane dialyzer which is perfused on the lumen side with the patient's blood and wherein a buffered aqueous solution comprising human serum albumin is passed in a continuous flow through the filtrate space of said first dialyzer, a second hollow fiber membrane dialyzer which removes water-soluble substances from the dialysate of said first dialyzer, and a third, integrated hollow fiber membrane dialyzer which is perfused with the retentate of second hemodialyzer and which allows the passage of certain amounts of albumin over the membrane wall into the filtrate space which is populated with adsorbent material. The system can be used for the treatment of acute liver failure and acute-on-chronic liver failure.

The composite artificial liver supporting system incldues a blood and plasma displacing unit for eliminating toxic matter and harmful matter and one biological artificial liver unit. The displacing unit includes plasma separator for separating patient's plasma and exhausting separated plasma, healthy blood leading in device with pump, valve and pipeline, and thermostat device to maintain the blood and plasma displacing unit at body's temperature. The biological artificial liver unit bioreactor comprising culture device and matter exchanger, blood and plasma flow stabilizer, culture liquid stabilizer and thermostat. Its using method includes the steps of detoxicating patient's blood and plasma, cutlruing exogenous cell, and utilizing the exogenous cell for synthesis, metabolism and matter exchange.

The invention discloses a bioartificial liver support system and a combined type liquid storage tank thereof, wherein the combined type liquid storage tank comprises a closed liquid inlet tank and a closed liquid return tank; the top of the liquid inlet tank is provided with a first liquid inlet and a first air pressure balancing hole; the bottom of the liquid inlet tank is provided with a first liquid outlet and a second liquid inlet; the top of the liquid return tank is provided with a third liquid inlet and a second air pressure balancing hole; the bottom of the liquid return tank is provided with a second liquid outlet and a third liquid outlet; and the second liquid outlet is communicated with the second liquid inlet by a first communicating pipe which is provided with a direction and flow control device. The invention can improve material interchange efficiency between hepatic failure blood plasma and a bioreactor, avoids futile cycle, does not need to depend on the chimney effect of pumps, has simple structure and stable operation and has improvement of the bioartificial liver support system. In the invention, volume of the liquid inlet tank and the liquid return tank can be adjusted according to specific requirements to suit clinical application.

The present invention relates to the field of bio-artificial liver technology. Particularly, the invention provides an integrated hybrid bio-artificial liver support system that provides the features of artificial liver assist devices with that of bio-artificial liver support systems.

The invention discloses an immortalized human liver cell line, a preparation method and an application thereof. The immortalized human liver cell line has the main function of primarily cultured human liver cell. The preparation method comprises the following steps of: transferring SV40T antigen and human telomerase catalyzed subunit gene into primarily cultured separated human normal liver cell by slow virus carrier; and sieving in a cloning way to obtain the immortalized human liver cell line. The immortalized human liver cell line also can be extrinsically amplified in large scales in a microcarrier way. The immortalized human liver cell line can be used for preparing a biological artificial liver support system and preparing the medicament for curing the liver failure.

The invention discloses a dual-cavity liquid storage tank for a biological artificial liver support system. The dual-cavity liquid storage tank comprises an inner cavity and an outer cavity, wherein the top of the outer cavity is provided with a first liquid inlet and a first air pressure balance hole; the top of the inner cavity is provided with a second liquid inlet and a second air pressure balance hole; the bottom of the inner cavity is provided with a first liquid outlet; the side wall, which is close to the bottom, of the inner cavity is provided with a second liquid outlet; the second liquid outlet passes through the outer cavity by means of a pipelike passage, and directly leads to the outside of the dual-cavity liquid storage tank from the inner cavity; and the pipelike passage is provided with a plurality of outer cavity side holes on the partial side wall of the outer cavity. The dual-cavity liquid storage tank for the biological artificial liver support system realizes that severe hepatitis plasma flows through a bioreactor for multiple times to form a high-efficiency circulation path, thereby playing better therapeutic effect. The proportion of volume sizes of the inner cavity and the outer cavity of the dual-cavity liquid storage tank for the biological artificial liver support system can also be reset according to clinical concrete practical requirements, and isexpanded or reduced so as to be applied to clinic treatment more reasonably.

The present invention discloses a method for preparing a human hepatic progenitor cell which is amplified and cultivated in vitro, including: a. separating the human hepatic progenitor cell; b. co-cultivating a feeder cell and the human hepatic progenitor cell separated from the step a by a medium having no serum on an extracellular matrix containing human fibrin sealant or other analogues, obtaining a human hepatic progenitor cell colony by amplification. The human hepatic progenitor cell colony is easy to separate from the surface of human fibrin sealant by the simple gelatinolytic band process. The human hepatic progenitor cell can be purified or / and subcultured by further single cell preparation technology process such as enzymatic degradation etc. The human hepatic progenitor cell prepared by the method provides good human hepatic progenitor cell source for hepatic cell treatment, including a hepatic cell transplantation and a bioartificial liver support system, cytotoxicity test platform in the drug screening, hepatitis virus infection and drug screening platform and the like.

The invention discloses a method for constructing a three-dimensional micro-liver tissue unit used in a bioartificial liver support system. It is characterized by adopting microcapsules prepared by sodium alginate-polycation to encapsulate porcine liver decellularized scaffold components, compounding hepatocytes, vascular endothelial cells and fibroblasts, and constructing functional three-dimensional micro-liver tissue units through cell self-assembly. And applied to the bioartificial liver support system. The invention is simple in operation and low in cost, and by simulating the interaction between cells and extracellular matrix, cells and soluble factors, and cells in the microenvironment of liver tissue in vivo, the self-assembly of liver cells, vascular endothelial cells and fibroblasts into The three-dimensional micro-liver tissue has good synthesis, secretion and detoxification functions, so it can be used as a micro-unit in a bioartificial liver support system.