38 results about "Pancreatic islet transplantation" patented technology

The invention provides human interleukin interleukin-2 (IL-2) / Fc fusion protein. The human IL-2 of the fusion protein comprises all sequences of a human IL-2 extracellular region; the Fc fragments comprise a hinge region, a CH2 region and a CH3 region; the human IL-2 / Fc sequences are fused directly or through a connection sequence; and the Fc fragments are human or animal IgG, IgM, IgD and IgA orsubtypes thereof. The ADCC and CDC effective factor action can be eliminated, and in addition, the human IL-2 / Fc fusion protein has the compatibility with a recombinant IL-2 receptor so that the half-life period is obviously prolonged and also has all the biological activity of the IL-2 receptor. The IL-2 / Fc obviously improves the humoral immune response stimulated by the hepatitis B vaccine and the immunity of the CD8+T cells targeted to the hepatitis B vaccine. Moreover, the balance immune (suppression) of the effective T cells and the regulatory t cells can be adjusted under the action of the cyclosporine A so that the pancreatic islet transplantation immune tolerance is induced.

The invention relates to CXCR1 and / or CXCR2 inhibitors for the preparation of a medicament for use as an adjuvant in the transplant of pancreatic islets in Type 1 diabetes patients. In particular, the compounds that can be used according to the invention have the following formula (I) in which R and R′ are as defined in the description.

A method for improving the health and viability of pancreatic islets and improving the outcome of pancreatic islet transplantations is described. The method includes incubating the islets with an IKVAV-containing laminin A chain peptide, such as PA22-2, either before or during the culturing of the islets in an RCCS bioreactor.

The invention provides a method of treating diabetes in a subject, comprising administering to the diabetic subject an immunotoxin, thereby reducing the subject's T-cell population, and administering to the subject pancreatic islet cells from a donor. The immune tolerance inducing treatment regimen, used optionally with adjunct immunosuppressive agents, prevents pancreatic islet cell rejection while maintaining long term islet cell function following xenogeneic and allogeneic pancreatic islet cell transplantation. Thus, the methods of the present invention provide a means for treating diabetes, wherein the need for exogenous insulin or immunosuppressive agents is decreased or eliminated. Also provided is a method of inhibiting a rejection response of a transplant recipient, comprising administering an immunotoxin during the peritransplant period, thereby transiently reducing the number of T-cell lymphocytes and promoting long-term survival of the transplant.

The present invention is directed to the identification of a biomarker specifically located in the plasma membrane of pancreatic beta cells. It was selected by a Systems Biology approach on Massively Parallel Signal Sequencing datasets obtained in human islets and Affymetrix microarray datasets on human islets, purified rat primary beta and non beta cells and insulinoma cells. Based on a set of specific features the biomarker is a unique candidate for imaging and targeting strategies to study the pancreatic beta cell mass in health and disease (T1 D, T2D, pancreatic cancers, obesity, islet transplantation, beta cell regeneration). The five specific features of the selected biomarkers are: 1) Preferentially expressed in pancreatic islets as compared to surrounding tissues; 2) Higher expression in pancreatic beta cells than in pancreatic alpha cells or than in other islet non-beta cells; 3) Expression levels in pancreatic beta cells are higher or comparable to glucokinase which is an enzyme specifically expressed in the pancreatic beta cell; 4) Located in the membrane and as such targetable with antibodies, peptides or small molecules which allows imaging, targeting and immunohistochemistry; and 5) Expression is not induced during the process of inflammation of the beta cell mass and the protein is not enriched in T-cells and dendritic cells or in other cells participating in the inflammation process.

An object of the present invention is to provide a method for preserving pancreatic islet, a container for preserving pancreatic islet and a kit for transplanting pancreatic islet in order to effectively preserve the pancreatic islet. The present invention presents; a method for preserving a liquid including pancreatic islet in a container for preserving pancreatic islet, wherein at least a part of the container wall face consists of a film having an oxygen permeation coefficient of 2500 cm3 / m2·day·atm or greater; a method for preserving a liquid including pancreatic islet in a container for preserving pancreatic islet, wherein at least a part of the container wall face consists of a film having a carbon dioxide permeation coefficient of 1000 to 20000 cm3 / m2·day·atm; and a container for preserving pancreatic islet for use in the above-described method, and a kit for transplanting pancreatic islet comprising the container for preserving pancreatic islet.

The invention discloses an adult sertoli cell-pancreas islet compound and a preparation method for the same, which solve the problem of influence on pancreas islet transplantation effect due to the transplant dysfunction because the pancreas islet separated and purified presently generates hypoxic-ischemic and immunological rejection reactions after being transplanted and then loses the function. The preparation method comprises the following steps of: 1, separating and purifying adult pancreas islet by adopting a semi-automatic filling and continuous density gradient methods; 2, separating and purifying adult sertoli cells by adopting a two-step digestion method; and 3, constructing the pancreas islet-sertoli cell compound by adopting a specific co-culture method. The adult sertoli cell-pancreas islet compound and the preparation method for the same disclosed by the invention have the advantage that pancreas islet cells and sertoli cells are coupled into a compound, the compound is used as a transplant, and the sertoli cells are attached to the surface of the pancreas islet, so as to improve the nutritional status of the pancreas islet, inhibit rejection reaction, and increase the survival rate of the pancreas islet; the operation is simple and convenient; and the success rate is high.

An object of the present invention is to provide a pancreatic islet transplantation technique that enables increase of graft survival rate of pancreatic islets after pancreatic islet transplantation, to maintain survival of pancreatic islets, and to reduce the number of transplanted pancreatic islets required for normalizing blood glucose level. When performing pancreatic islet transplantation, by transplanting pancreatic islets and adipose tissue-derived stem cells together, it is possible to significantly improve graft survival rate of transplanted pancreatic islets, and reduce by half the number of transplanted pancreatic islets required for normalizing blood glucose level.

The present invention discloses an in vitro method wherein mammalian beta-cell differentiation can be induced in dedifferentiated exocrine pancreatic cells in a medium comprising ligands of the EGF receptor and the GP130 receptor, such as EGF and LIF. Insulin secreting cells, obtainable by this method, provide a means for the treatment of diabetes by islet transplantation.

A method for forming langerhans' islet like structure by inlet cells differentiated from dry cells by extracorporal induction. The inlet cells differentiated from dry cells are placed in a culture dish that has been treated by silane, the cells are induced to form langerhans' islet like structure by suspension culturing way with a cell culture medium containing 20% fetal bovine serum, out-cell substrate, calcium ion of certain concentration and ATP. The invention has the following advantages: 1. the method is simple, the induction time is short, the forming rate of langerhans' islet like structure is high; 2. the formed langerhans' islet like structure is very much similar with natural langerhans' islet, and can be steadily positioned in sinus hepaticus by transplanting through a portal; 3. the formed langerhans' islet like structure has an obvious diolame, and substrate component very similar to natural langerhans' islet. The langerhans' islet like structure formed by the method can meet the quality for transplanting langerhans' islet.

An objective of the present invention is to provide effective methods for suppressing rejection in organ transplantation, in particular, pancreatic islet transplantation which is useful in treating diabetes. The present invention demonstrated that antibodies against HMGB-1 suppressed the rejection in pancreatic islet transplantation and promoted the survival of grafted pancreatic islets. Thus, the present invention provides agents that comprise an anti-HMGB-1 antibody for suppressing rejection in organ transplantation.

The present invention provides methods that increases the graft survival rate of pancreatic islets after pancreatic islet transplantation, maintains the survival of pancreatic islets ex vivo, and reduce the number of transplanted pancreatic islets required for normalizing blood glucose levels. When performing pancreatic islet transplantation, by contacting pancreatic islets with stem cells or by transplanting pancreatic islets and stem cells in contact with each other, it is possible to significantly improve graft survival rate of transplanted pancreatic islets and reduce the number of transplanted pancreatic islets required for normalizing blood glucose levels. The invention also provides compositions for pancreatic islet transplantation comprising the islets and the stem cells or conditioned medium from stem cell culture islets. Thus, the composition and methods are useful for treating diabetes.

A method for improving the health and viability of pancreatic islets and improving the outcome of pancreatic islet transplantations is described. The method includes incubating the islets with an IKVAV-containing laminin A chain peptide, such as PA22-2, either before or during the culturing of the islets in an RCCS bioreactor.

The invention discloses application of P glycoprotein as a protection factor to influence of INS-1 832 / 13 cell insulin secretion. The action mechanism of the P glycoprotein on rat insulinoma cell INS-1 832 / 13 cell insulin secretion is shown by researches. As found by in-vitro test, the P glycoprotein can further activate a PKA (Protein Kinase A) signal transduction pathway by increasing in-cell cAMP (Cyclic Adenosine monophosphate) content in order to improve the PKA and CERB activity. Meanwhile, the existence of interaction between the P glycoprotein and a lipid raft relevant protein, Caveolinl, an L-shaped calcium ion channel protein 1.2 (Cav1.2), a potassium ion channel protein (Kir6.2) and adenylate cyclase is verified by the experiment, so that the secretion of insulin is influenced.A theoretical basis is laid for the research of pancreatic islet protection factors, and improvement of pancreatic islet transplantation clinical outcome.

The invention discloses an application of kaempferol in medicines for inhibiting rejection reaction of a receptor on organ transplantation. The invention discloses pharmacological effects of kaempferol in inhibiting rejection reaction of organ transplantation in the body of a receptor for the first time; and moreover, optimal effects can be achieved when kaempferol is combined with low-dose cyclosporin for a short time, and long-term survival of an islet graft in the receptor can be induced, so that various side effects caused by using full-dose cyclosporin for a long time can be avoided, the economic burden of patients brought by long-term anti-rejection treatment can also be lightened, and the long-term high-quality life of organ transplantation patients can be further facilitated. The invention also discovers an immune adjustment action mechanism of kaempferol, namely that kaempferol can be used for significantly increasing the number of regulatory T lymphocytes in the body of the receptor and reducing the gene expression of an islet graft IL-6 in the body of the receptor, so that the effects of resisting inflammation and resisting rejection reaction can be achieved.

The present invention discloses an in vitro method wherein mammalian beta-cell differentiation can be induced in dedifferentiated exocrine pancreatic cells in a medium comprising ligands of the EGF receptor and the GP130 receptor, such as EGF and LIF. Insulin secreting cells, obtainable by this method, provide a means for the treatment of diabetes by islet transplantation.

The invention discloses an islet organ with an immune tolerance function as well as a preparation method and an application thereof. The preparation method comprises the following steps: mixing islet-containing cell clusters, mesenchymal stem cells, an immunosuppressant and a scaffold material according to a volume ratio of 1: 1: 0.5: 2.5 to prepare a hydrogel material, and carrying out a cross-linking reaction for 1 h; the islet organ prepared by the invention can well solve the problems of immunological rejection and early ischemia of a host, prolong the function and survival time of an islet graft, improve the effect of clinical islet transplantation, and relieve the pain of patients suffering from type I diabetes in need of long-term insulin treatment.

An object of the present invention is to provide a pancreatic islet transplantation technique that enables increase of graft survival rate of pancreatic islets after pancreatic islet transplantation, to maintain survival of pancreatic islets, and to reduce the number of transplanted pancreatic islets required for normalizing blood glucose level. When performing pancreatic islet transplantation, by transplanting pancreatic islets and adipose tissue-derived stem cells together, it is possible to significantly improve graft survival rate of transplanted pancreatic islets, and reduce by half the number of transplanted pancreatic islets required for normalizing blood glucose level.

The present invention is directed to the identification of a biomarker specifically located in the plasma membrane of pancreatic beta cells. Based on a set of specific features the biomarker is a unique candidate for imaging and targeting strategies to study the pancreatic beta cell mass in health and disease (T1D, T2D, pancreatic cancers, obesity, islet transplantation, beta cell regeneration).

The invention discloses an oligonucleotide for inhibiting a blood-mediated inflammatory reaction in pancreatic islet transplantation. The oligonucleotide comprises 7 to 75 nucleotides, at least comprises 3 three continuous achiral 5' to 3' nucleoside-triphosphate bonds, comprises a 5'-end untranslated region, a translation initiation region, a 3'-end untranslated region and / or a translation termination region which are complemented for a TF gene, and has the melting temperature of between 75 DEG C and 115 DEG C under the concentration of 1mmol. The oligonucleotide can be a ribose oligonucleotide or a deoxyribose oligonucleotide, can be modified chemically and can be used for preparing medicinal compositions for resisting the blood-mediated inflammatory reaction in the islet transplantation.

An object of the present invention is to provide a composition containing a pancreatic islet, a cell structure containing a pancreatic islet or a pancreatic islet cell, a pancreatic islet transplantation kit, a pancreatic islet transplantation treatment agent, and a hypoglycemic agent which improve at least one of glucose sensitivity or blood sugar level-reducing performance after transplantation, and to provide a composition containing a pancreatic islet, a kit containing a pancreatic islet, a pancreatic islet cell transplantation treatment agent, and a hypoglycemic agent which can improve glucose sensitivity. According to the present invention, a composition including A: a cell structure which contains a biocompatible macromolecular block and at least one kind of cell and in which a plurality of the above-described macromolecular blocks are arranged in gaps between a plurality of the above-described cells; and B: a pancreatic islet, and a composition containing a pancreatic islet; and a spheroid formed of at least one type of stem cell are provided.

Embodiments of the disclosure pertain to the treatment of diabetes through replacement of insulin producing cells. In specific embodiments, the disclosure encompasses the use of cellular adjuvants to enhance survival, engraftment and tolerogenesis of insulin-producing cells. In certain cases the disclosure concerns the manipulation of a hepatic microenvironment to promote immunological tolerance at an enhanced level to allow for integration of allogeneic insulin-producing cells. Particular embodiments utilize fibroblasts to enhance immunological tolerance for insulin-producing cells upon engraftment.

The present invention is directed to the identification of a biomarker specifically located in the plasma membrane of pancreatic beta cells. Based on a set of specific features the biomarker is a unique candidate for imaging and targeting strategies to study the pancreatic beta cell mass in health and disease (T1D, T2D, pancreatic cancers, obesity, islet transplantation, beta cell regeneration).

The invention relates to CXCR1 and CXCR2 inhibitors for the preparation of a medicament for use as an adjuvant in the transplant of pancreatic islets in Type 1 diabetes patients. In particular, the compounds thagt can be used according to the invention have the following formula (I) in which R and R' are as defined in the description.

The invention provides a device for culturing pancreas islet cells in pancreas islet transplantation, and relates to the field of pancreas islet transplantation. The pancreas islet cell culture device in pancreas islet transplantation comprises a base, a connecting frame is in sliding connection with a side frame, and a pressing and discharging assembly is arranged between a rack rod and a box body. According to the pancreas islet cell culture device in pancreas islet transplantation, the output end of the motor drives the output shaft to rotate, the rotating plate rotates by 90 degrees at the opening in the middle of the partition plate, the traction rope drives the piston disc to slide between the partition plate and the box wall of the box body at the same time, and then air can be automatically supplemented into the box body at regular time; therefore, the oxygen content in the box body can be kept in a proper state in a closed temperature control state; temperature is sensed through the dispersing fins and conveyed into the strip-shaped cavity through the temperature guide strip, the strip built-in sliding piece drives the slender rod to slide relative to the vertical cavity, the contact piece at the top end of the slender rod slides to abut against the long contact strip, and then the refrigerating strip piece works to refrigerate and adjust the environment temperature in the box body.

The invention belongs to the technical field of cell differentiation, and particularly relates to a method for differentiating peripheral blood stem cells into endoderm cells and application of the method. According to the invention, peripheral blood stem cells are subjected to induced culture in the presence of BM, Activin A, Wnt3a, TGF-b, LIF, TNF-a, IFN-a, vinterferron-alpha, beta, gamma, B-27 and N2, such that endoderm cells are obtained. The technology is a technical supplement for differentiating the endoderm cells into the islet cells, and the clinical application range of differentiating the stem cells into the islet cells and applying the stem cells to islet transplantation is widened. The technology is expected to solve the islet cell source problem and the islet transplantation heterologous problem, and the clinical effect of islet transplantation and the long-term survival of the graft are improved.

The invention relates to the field of pancreas islet transplantation, in particular to application of ISL1 in preparation of a medicine for inhibiting early ferroptosis of transplanted pancreas islet and a cell. Islet cells for overexpressing ISL1 are constructed by using the adenovirus to obtain islet cells for overexpressing ISL1. The expression change conditions of ferroptosis-related proteins (GPX4 and ACSL3) and apoptosis-related proteins are detected by using the overexpression and the knock-down of the ISL1 in the rat beta cell INS-1 through the lentivirus so as to determine that the ISL1 has the protection effect on the STZ induced INS-1 ferroptosis. The adenovirus of EcoRI MCS-ISL1 is utilized to construct rat and human islet cells for overexpressing ISL1, and it is clear that ISL1 inhibits transplanted islet ferroptosis by promoting expression of ACSL3 in the islet cells. A solid foundation is laid for improving survival of transplanted pancreas islet by genetically modified human pancreas islet cells and widely applying pancreas islet transplantation to clinic. The constructed cell can be used for experiments and pancreas islet transplantation possibilities.