72 results about "Beta cell" patented technology

The invention provides a pancreatic islet organ capable of efficiently maintaining pancreatic islet beta cell identity and a preparation method and application thereof. Specifically, the invention provides the preparation method for the in-vitro pancreatic islet organ, and the preparation method comprises the following steps: carrying out induced differentiation culture on the ZnT8-knocked-out pluripotent stem cells, so as to obtain the mature pancreatic islet organ. The invention also provides a corresponding transplantation composition and application thereof. The invention discloses that ZnT8 knockout is a key factor for effectively maintaining the identity stability of beta cells in pancreatic islet organs. In addition, the pancreas islet beta cell identity maintenance agent is combined with the ZnT8-knocked-out pancreas islet organ for use, so that the identity stability of the pancreas islet organ beta cell can be obviously maintained. The invention provides a new strategy for transplantation treatment of type 2 diabetes, and has excellent clinical transformation value.

The invention relates to the technical field of biological pharmacy, in particular to application of a recombinant protein DEL-1 in preparation of a medicine for resisting pancreatic beta cell inflammation. The recombinant protein DEL-1 has a remarkable inhibition effect on pancreatic beta cell inflammatory response induced by high glucose and high fat. Experiments show that in an islet beta cell inflammation model constructed by combining high glucose with palmitic acid, DEL-1 can significantly reduce the expression level of inflammatory factors such as IL-1beta, IL-6, TNF-alpha and the like. The DEL-1 is proved to have a definite effect of resisting pancreatic beta cell inflammation.

Disclosed herein include methods, compositions, and kits suitable for use in cell therapy. In some embodiments, there are provided methods and compositions for differentiating stem cells into pancreatic beta cells capable of producing insulin.

The present disclosure relates to a method of generating pancreatic lineage cells, e.g. islet-like cell aggregates comprising pancreatic beta cells, comprising the steps of providing a single cell suspension of a population of endocrine progenitor cells (EP), allowing the EP cells in the single cell suspension to form 3D structures, and culturing the cells under conditions allowing differentiation into pancreatic mono-hormonal beta cells. The present disclosure also relates to islet-like cell aggregates obtainable by said method and their medical use.

The application relates to a construction method of a Mettl3 transgenic mouse model with specific knockout, enriches the understanding of the function and action mechanism of Mettl3 in mature pancreatic islet beta cells, and provides a new thought and target for the pathogenesis and treatment of diabetes.

The invention provides a high-stress-tolerance pancreas islet organ as well as a preparation method and application thereof. Specifically, the invention provides a method for preparing pancreas islet organs. The invention also provides a use of a reagent combination comprising (a) a pancreatic islet organ and (b) a compound of formula I or a pharmaceutically acceptable salt thereof. In the presence of the compound shown in the formula I or the pharmaceutically acceptable salt thereof, pancreatic endocrine progenitor cells are cultured, so that the increase of the differentiation proportion of pancreatic beta cells is promoted, and pancreatic islet organs with high stress tolerance are obtained; according to the present invention, the combination of the pancreatic islet organ and the compound represented by the formula I or the pharmaceutically acceptable salt thereof can significantly improve and alleviate the integration stress reaction generated during the pancreatic islet organ transplantation compared to the only transplantation treatment, such that the pancreatic islet beta cell identity loss is resisted, and the stress tolerance of the pancreatic islet organ is significantly improved; therefore, the invention provides a new strategy for the treatment of diabetes, and has a wide application prospect.

Provided herein are systems of modulating gene expression, methods of use thereof, and cells engineered thereof for the purpose of differentiating cells, for example beta cells.

The invention relates to a method of differentiating pancreatic bi-potent progenitor cells into beta cells comprising cultivating pancreatic endocrine precursor cells in a medium that promotes the cAMP signalling pathway that lies downstream of apical-basal polarity in endocrine precursors, which can be used to increase the differentiation of progenitor cells into beta cells. Furthermore, the present invention relates to a method of enriching and / or isolating one or more cells expressing a marker of apical-basal polarity, thereby isolating beta cells, and to a method of producing a population of beta cells from a population of human embryonic stem cells. Furthermore, the present invention relates to a population of beta cells obtainable by the method, a pharmaceutical composition comprising the beta cells, a cell culture of progenitor cells in a medium comprising a cAMP agonist, a complex comprising a beta cell bound by the binding agents specific for CD133 and CD49a, and a use of specific binding partners for isolating beta cells.

This provides an unlimited supply method for human β-cells from stem cells. [Solution] Compositions and methods for promoting the differentiation of stem cells into beta cells using one or more epigenetically modified compounds are disclosed herein. The disclosure also relates to compositions and methods for selecting and enriching differentiated beta cells. The disclosure also relates to compositions and methods for irradiating a cell population to reduce proliferation. In some embodiments, methods are provided herein, comprising the step of contacting a population of pancreatic progenitor cells or their precursors with an epigenetically modified compound, wherein the contact step results in a population of endocrine cells in which the proportion of chromogranin A-positive (CHGA+) cells or C-peptide-positive and NKX6.1-positive (C-PEP+, NKX6.1+) cells is increased compared to a corresponding population of endocrine cells that have not been contacted with the epigenetically modified compound.

The present invention relates to a test kit for performing an assay to detect and measure at least one autoantibody molecule in a subject developing type 1 diabetes (T1D). The invention more specifically relates to a recombinant antigen molecule fused to a bioluminescent reporter protein to detect an autoantibody molecule against a self-antigen. Said self-antigen is preferably expressed by pancreatic islet beta cells and include insulin, proinsulin, Glutamate decarboxylase 65, islet antigen 2, and Zinc transporter 8. More specifically, the present invention relates to an assay comprising a set of at least three recombinant antigen molecules in a single composition, the antigen molecules being selected from the list comprising recombinant human Glutamate decarboxylase 65, recombinant human islet antigen 2, recombinant human Zinc transporter 8, recombinant human insulin, and recombinant human proinsulin. The invention further relates to methods for determining the presence and / or level of at least one autoantibody molecule in a sample from a human subject developing T1D using said recombinant antigen molecules. According to the invention, the presence, absence, or amount of one or more autoantibody molecules against said self-antigens is determined with a luciferase immune precipitation system (LIPS) assay or a modified version of a LIPS assay, i.e., a solid phase capture LIPS (scLIPS) assay.

The invention discloses a stem cell medicine for pancreas islet repair and application, and belongs to the technical field of stem cell biology, and the stem cell medicine for pancreas islet repair is prepared by compounding a carrier, pancreatic progenitor cells and pancreas islet-like cells in proportion. The problems that in the prior art, due to the fact that stem cells are unstable in differentiation efficiency, poor in synergistic effect and poor in biocompatibility, islet injury cannot be repaired, and diabetes cannot be treated are solved. According to the present invention, the dual mechanisms of endogenous beta cell repair and exogenous beta cell supplement are adopted, and the beta cell function recovery and the group structure reconstruction are synchronously achieved through the reasonable ratio, such that the in-vivo blood glucose of the mouse is significantly reduced, the beta cell number and the glucose tolerance dose of the mouse are increased, and the low immunogenicity and the high anti-inflammatory property are simultaneously provided. The compound can be used for treating type I and type II diabetes mellitus, improving the insulin secretion function and relieving local inflammatory response of pancreas by promoting pancreas islet beta cell proliferation, and has application potential in treatment of type I and type II diabetes mellitus and pancreas islet repair.

The invention belongs to the technical field of biological medicine, and particularly relates to application of beta cell protein in preparation of medicine for preventing and treating abortion. Research finds and verifies for the first time that application of beta cell protein (BTC) promotes invasion and tubulation processes of extravillus trophoblast cell line-HTR8 cells, BTC has an obvious rescue effect on embryo absorption in abortion model mice in early and middle stages of pregnancy, and BTC is injected into the abortion model mice in an intraperitoneal cavity in early and middle stages of pregnancy to increase placenta weight, so that the abortion model mice in early and middle stages of pregnancy have an obvious rescue effect on embryo absorption. Therefore, the BTC has a certain treatment effect on the abortion, so that the BTC has a good practical application value.

The disclosure provides polypeptides that specifically bind to HLA-DQ8 for treating Type 1 Diabetes (TID) and methods using same for reducing autoimmune destruction of pancreatic islet beta cells. In particular, the present disclosure relates to peptides containing at least one D-amino acid that are capable of blocking the presentation of antigenic islet peptides (e.g., lnsB:9-23) by HLA-DQ8, and to their uses, especially as it relates to the prevention and / or treatment of TID.

Disclosed herein are methods for directing the differentiation of stem cells towards a specific cell type.

The invention relates to the technical field of biology, in particular to application of SAFit2 in preparation of a reagent for improving pancreas islet dysfunction. The invention discovers that SAFit2 has a remarkable improvement effect on insulin secretion dysfunction in a high-glucose and high-fat induced islet injury model. Experiments show that in a high glucose (33 mM) combined palmitic acid (500 [mu] M) injury model, the SAFit2 can significantly improve the insulin secretion function of the pancreas islet. Specifically, the SAFit2 is pretreated, the glucose stimulated insulin secretion (GSIS) index of the pancreas islet and the intracellular insulin content are remarkably increased, insulin secretion under high glucose stimulation is promoted, and the SAFit2 is proved to have the effect of promoting the insulin secretion function of the pancreas islet beta cells.

Disclosed herein are hypoimmunogenic stem cell-derived β cells for use in various applications, such as cell therapy.

The invention provides a preparation method and application of an anti-IL-11 antibody modified Treg cell, and belongs to the technical field of genetic engineering.The preparation method of the anti-IL-11 antibody modified Treg cell comprises the steps that after the Treg cell and umbilical cord blood pluripotent stem cells are co-cultured, the Treg cell is separated and recycled, an anti-IL-11 antibody is adopted for modification, and the anti-IL-11 antibody modified Treg cell is obtained; the nucleotide sequence of the anti-IL-11 antibody is as shown in SEQ ID NO. 2 in the sequence table. In the co-culture process, stem cells are used for providing an immune microenvironment, promoting Treg cell amplification and enhancing the inhibition ability of Treg cells, and obtaining the specific recognition ability of pancreas islet beta cell antigens, so that autoimmune attacks are inhibited more accurately; the nucleotide sequences of the heavy chain and the light chain of the anti-IL-11 antibody are optimized, and the anti-IL-11 antibody has higher efficacy in treatment of diabetic mice.

The invention belongs to the technical field of medicines and health-care foods, and particularly relates to a quercetin-cordyceps militaris polysaccharide solid self-nano emulsification drug delivery system as well as a preparation method and application of the quercetin-cordyceps militaris polysaccharide solid self-nano emulsification drug delivery system. The drug delivery system is prepared by mixing cordyceps militaris polysaccharide and a liquid quercetin self-nano emulsification precursor system, and spray-drying; the solid-to-liquid ratio of the cordyceps militaris polysaccharide to the liquid quercetin self-nano emulsification precursor system is 1 g: 3 mL-3 g: 1 mL. According to the present invention, the QUE-CMP-S-SNEDDS provided by the present invention has characteristics of good slow release ability and high oral bioavailability. Animal experiment results prove that the QUE-CMP-S-SNEDDS can remarkably reduce the fasting blood glucose level of a diabetic model mouse, effectively improve the pancreatic beta cell function of the mouse, and meanwhile, can remarkably relieve the pathological state of liver lipid metabolism disorder of the mouse.

The invention discloses an application of miR-100 sponge in preparation of a medicine for treating type 2 diabetes mellitus. The miR-100 sponge can inhibit miR-100 in a targeted manner and close the expression of miR-100 in beta cells. The nucleic acid construct is further prepared from the nucleic acid construct, AAV8-mmu-miR-100 Sponge (AAV-Sponge) is injected into pancreatic ducts of obese diabetes mellitus mice, after treatment is conducted for 4 weeks, it is found that the sugar tolerance of the mice in a treatment group is improved, the GSIS function of beta cells is improved, and the nucleic acid construct is expected to be further applied to preparation of the medicine for treating the type 2 diabetes mellitus. The problems that current treatment methods for type 2 diabetes mellitus are deficient and the treatment cost is high are solved.

The present disclosure is generally directed to the use of biomaterial scaffolds engineered with SA-FasL for the transplantation of stem cell derived β-cells as a treatment for Type I diabetes. Early engraftment post-transplantation and subsequent maturation of these β-cells may be limited by the initial inflammatory response, which impacts the ability to sustain normoglycemia at long times. The survival and development of immature hPSC-derived β-cells transplanted on poly(lactide-co-glycolide) (PLG) microporous scaffolds into the peritoneal fat, a site being considered for clinical translation, was investigated. The scaffolds were modified with biotin for binding of a streptavidin-FasL (SAFasL) chimeric protein to modulate the local inflammatory microenvironment. The presence of FasL impacted infiltration of monocytes and neutrophils and altered their phenotypic response. Conditioned media generated from scaffolds explanted at day 4 did not impact hPSC-derived β-cell survival and maturation in vitro, which was not observed with unmodified scaffolds. Following transplantation, β-cell viability and differentiation were improved with SA-FasL modification. A sustained increase in insulin positive cell ratio was observed with SA-FasL modified relative to unmodified scaffolds. These results demonstrate that SA-FasL-modified scaffolds can mitigate initial inflammatory response and enhance β-cell engraftment and differentiation.

Provided herein are methods of manufacturing β cells in vitro. Also provided herein are methods of treating a disease in a subject comprising administering the β cells manufactured in vitro to the subject. Also provided herein are methods of differentiating stem cells into β cells.

The present application provides a traditional Chinese medicine composition with blood sugar lowering efficacy and a preparation method thereof, and belongs to the technical field of traditional Chinese medicines; the traditional Chinese medicine composition is prepared from the following raw materials in parts by mass: birch juice 140-200 parts, jujube fruit 20-40 parts, rehmannia 20-40 parts, adenosma 18-26 parts, periploca 18-26 parts, ophiopogon 18-26 parts, bamboo shavings 12-19 parts, leech 12-19 parts, psyllium 12-19 parts, dogwood 10-14 parts, gordon euryale seed 10-14 parts. In the traditional Chinese medicine composition, the blood sugar lowering effect is mainly achieved by repairing the function of islet beta cells, promoting the regeneration of islet beta cells, improving sugar metabolism, increasing the sensitivity of insulin or improving insulin resistance, so that the overall prescription achieves the effects of invigorating the spleen and lung, nourishing yin and reducing fire, benefiting the stomach and producing saliva, astringing the spleen essence, promoting transportation and transformation, tonifying the kidney and strengthening the body, and relieving polydipsia and restlessness.

The invention discloses a fusion protein for regulating and controlling functions of pancreatic beta cells based on an optogenetics technology and application of the fusion protein, and relates to the technical field of biology. The fusion protein Opto LOVTRAP disclosed by the invention has very high temporal-spatial resolution, and rapid and accurate control on a single cell can be realized by adjusting blue light; opto LOVTRAP has reversibility, can effectively inhibit a pancreatic beta cell Ca < 2 + > channel under a dark condition, and can quickly stop playing a role after being stimulated by blue light, so that the purpose of reversibly and accurately regulating insulin secretion is achieved. Opto LOVTRAP is targeted to regulate the concentration of Ca < 2 + > in cells, and is a final triggering factor for release of pancreas islet vesicles, so that the opto LOVTRAP is not influenced by the KATP function, and the purpose of breaking through the bottleneck of a traditional clinical treatment mode is achieved.

The present disclosure provides novel methods for increasing β-cell viability in islets by delivering RLIP76 polypeptides or GSTA4 polypeptides, or a combination thereof; or RLIP76 polynucleotides or GSTA4 polynucleotides, or a combination thereof, to the islets. The disclosure also provides novel methods for treating a disease or condition in a subject, such as type 1 diabetes mellitus, by delivering RLIP76 polypeptides or GSTA4 polypeptides, or a combination thereof; or RLIP76 polynucleotides or GSTA4 polynucleotides, or a combination thereof, to islets and transplanting the islets into the subject to treat the disease or condition. Kits and compositions including RLIP76 polypeptides or GSTA4 polypeptides, or a combination thereof; or RLIP76 polynucleotides or GSTA4 polynucleotides, or a combination thereof, are also provided to increase β-cell viability.

The present disclosure provides a use of a substance targeting BRD4 in the preparation of a product related to diabetes. In the present disclosure, it is found that the expression of BRD4 in human diabetic beta cells is significantly reduced, and BRD4 plays an important role in maintaining beta cell maturation and differentiation, and long-term and acute BRD4 deficiency can lead to reduced insulin secretion and down-regulation of differentiation markers, highlighting the key role of BRD4 in pancreatic beta cells, providing a target BRD4 that has a significant impact on diabetes, so that substances targeting BRD4 can help to assess the susceptibility of diabetes, screening, prevention, intervention and treatment of diabetes.

The application discloses a kind of potential metabolic state modeling gestational diabetes risk assessment and intervention decision method, it is related to medical information technology field, including: first, obtain the minimum metabolic modeling data structure containing individual static information, follow-up observation and intervention data;Second, initialize the latent metabolic state vector formed by insulin sensitivity, beta cell compensatory capacity, fat burden and other latent variables;Then, an observation mapping and state updating mechanism is established, and the state vector is dynamically corrected and updated using follow-up observation and intervention data;Subsequently, based on the updated vector, a metabolic system stability index is calculated to assess patient risk stratification;Finally, by counterfactual reasoning, the state evolution under different hypothetical intervention scenarios is simulated, and the intervention priority and recommendations are output.The present application realizes early identification and precise intervention of risk through microscopic modeling and deduction of latent metabolic state, significantly improving the effectiveness of perinatal and postpartum health management.

The invention relates to the field of biology, in particular to application of tauroursodeoxycholic acid in preparation of a medicine for promoting function maturation of islet organs. The specific effect of tauroursodeoxycholic acid in promoting functional maturation of iPSC-derived islet-like organs is found and verified for the first time, and a brand new treatment thought is represented. The beta cell functional gene expression and glucose stimulation response capability of the sc-islet can be remarkably improved only by performing TUDCA treatment for 96 hours, and the function maturation period is greatly shortened. The obvious effect can be achieved by adopting the low-dose TUDCA with the concentration of 25-100 ng / mL, the cost is reduced, and the potential toxicity risk is reduced. Key indexes (functional gene expression and glucose response) of beta cell maturation are directly targeted, and a high-quality cell model is provided for research and treatment of diabetes mellitus.

Provided herein are methods related to delivery of stem cell-derived cell therapies, including stem cell derived islet cell therapies, and related compositions, uses and articles of manufacture. In particular embodiments, the methods relate administering stem cell-derived islet cells. In some embodiments, the subject has a beta cell related disorder, such as diabetes (e.g. Type I diabetes).

The invention discloses a pancreatic beta cell precursor cell transplantation chip based on human-derived iPSC (induced pluripotent stem cell) as well as a preparation method and application of the pancreatic beta cell precursor cell transplantation chip. The chip is composed of beta cell precursor cells (expressing Pdx1, Nkx6.1 and NeuroD1) and a porous degradable bracket (PCL / hyaluronic acid composite material), wherein the beta cell precursor cells (expressing Pdx1, Nkx6.1 and NeuroD1) are obtained by performing four-stage induction on autologous iPSC. The preparation method comprises the steps of autologous iPSC acquisition, beta cell precursor cell induction, three-dimensional bracket preparation and chip assembly. After the chip is implanted into the pancreas of a patient through minimally invasive surgery, precursor cells are differentiated into mature beta cells in vivo, insulin is secreted, the stent is gradually degraded, the pancreas islet function can be fundamentally improved, and the chip is used for treating type I and type II diabetes mellitus. The invention avoids immunological rejection, improves cell survival and functional stability, and has significant clinical transformation value.