67 results about "Activin a" patented technology

The invention belongs to the technical field of regenerative medicine, and particularly relates to a method for generating vascular endothelial cells by inducing pluripotent stem cells to differentiate in vitro. The method comprises the following steps: carrying out first culture on pluripotent stem cells in a differential medium I to obtain cells A; carrying out second culture on the cell A in a differential culture medium II, and differentiating and directionally forming an endoderm cell B; performing third culture on the endoderm cells B in a differential culture medium III to obtain differentiated cells C; carrying out fourth culture on the differentiated cells C in a differentiation culture medium IV, and differentiating to form differentiated cells D; carrying out fifth culture on the differentiated cells D in a differential culture medium V, and differentiating to obtain vascular endothelial cells; wherein the differential culture media I-V do not contain activin A, VEGF (vascular endothelial growth factor) and BMP4 (bone morphogenetic protein 4). The method can improve the differentiation efficiency of the IPS cells to the vascular endothelial cells, and has a wide prospect in the cell therapy industry.

Provided are diagnostic and / or screening tests, assays and devices for preeclampsia (PE). The diagnostic and / or screening tests, assays and devices include test antibodies for activin A and / or inhibin A. The PE diagnostic and / or screening tests, assays and devices are capable of detecting activin A and / or inhibin A in a sample at a concentration of less than about 60 pg / mL. Corresponding methods of diagnosing and / or screening for PE are provided.

Disclosed herein are therapeutic uses of myostatin-selective inhibitors, such as myostatin-selective inhibitors, for treating metabolic disorders, such as obesity. Data presented herein support the notion that selectively targeting myostatin without inhibiting Activin A can achieve equivalent or enhanced efficacy when used in conjunction with a GLP-1 receptor agonist in improving body composition, as compared to broadly antagonizing the ActRII pathway in conjunction with a GLP-1 receptor agonist. Administration of a myostatin-selective inhibitor can prolong the effect of semaglutide on fat mass loss. Moreover, administration of a myostatin-selective inhibitor can elicit positive effects on bone in all parameters evaluated, indicating that diet- or inflammation-induced bone atrophy may be prevented by selective inhibition of the myostatin pathway.

The invention provides a method for 3D differentiation of pluripotent stem cells into definitive endoderm cells by using a bioreactor, a differentiation medium and a differentiation factor A / B are also included, and the medium and the differentiation factor A / B comprise the following components: an MCDB131 medium, 2.44 mM glucose, 29.28 mM sodium bicarbonate, 2% of HSA, 1% of GlutaMAX, 250 [mu] M Vitamin C, 0.002% of ITS-X, 1% w / v of Polyethylene glycol (PEG), 1 mg / ml of Heparin Sodium salt, 100 ng / mL of Activin A and 3 [mu] M of CHIR99021. The method uses the bioreactor to differentiate the pluripotent stem cells into the stereotyped endoderm cells in a 3D suspension manner, is simple to operate and high in differentiation efficiency, provides technical support for scientific research and industrial large-scale production, and has a good application prospect.

The invention relates to the technical field of biology, in particular to a method for efficiently obtaining human definitive endoderm cells in vitro, which comprises the following steps: S1, inoculating human pluripotent stem cells into matrigel, and performing maintenance culture for 16-24 hours by using a stem cell maintenance culture medium; s2, from Day-2 to Day-1, absorbing and abandoning the stem cell maintenance culture medium, adding a pretreatment culture medium for culture, and changing the pretreatment culture medium once every day; the pretreatment culture medium is a stem cell maintenance culture medium added with dimethyl sulfoxide; s3, carrying out Day0 to Day2, absorbing and abandoning the pretreatment culture medium, adding a definitive endoderm differential culture medium, carrying out induced culture, and changing the definitive endoderm differential culture medium once a day; the definitive endoderm differential culture medium is an RPMI1640 culture medium added with fetal calf serum and activin A; s4, Day3, obtaining the required human definitive endoderm cells, and solving the problems that the existing definitive endoderm differentiation efficiency and cell population purity are limited and are influenced by batch-to-batch variation.

The present invention relates a pharmaceutical composition for alleviation, treatment, and prevention of sarcopenia, including, as an active ingredient, a microorganism transformed with a cell surface display vector operably linked with a gene encoding myostatin and activin A proteins.

The invention belongs to the technical field of cell biology, and particularly relates to a feeder-layer-free and serum-free bovine embryonic stem cell culture medium, a culture system and a culture method. The bovine embryonic stem cell culture medium comprises a conditioned culture medium and additives, the additives are IWR-1 and activin A, and the concentrations of the IWR-1 and the activin A in the conditioned culture medium are 2.5-5 [mu] M and 20-25 ng / mL respectively; the culture system comprises a bovine embryonic stem cell culture medium, gelatin with the mass concentration of 0.1-0.2% and a subculture medium, and the gelatin with the mass concentration of 0.1-0.2% is used for providing an attachment matrix for bovine embryonic stem cells; the subculture medium is prepared by adding Y27632 into a bovine embryonic stem cell culture medium. The cost of the extracellular matrix is reduced, and the feeder-layer-free bovine embryonic stem cell has high single cell passage efficiency and is convenient for gene editing operation.

The invention discloses a method for inducing iPSCs (induced pluripotent stem cells) to directionally differentiate into vascular endothelial cells by using a small molecule compound and cell factor composition, which is characterized in that iPSCs cells are used as starting cells, and a vascular endothelial cell differentiation scheme completely dependent on chemical small molecule and cell factor stimulation is established. An E6 culture medium containing CHIR-99021, BMP4 and Activin A is utilized to induce mesoderm progenitor cells, an E6 culture medium containing VEGFA (vascular endothelial growth factor A), FGF-2, 8-Bromoadenosine 3 ', 5'-cyclic monophosphate monophosphate, SB431542, Forskolin and Melatonin is utilized to induce the endothelial cells, and an E6 culture medium containing VEGFA, FGF-2 and Hydrocortisone is utilized to further induce and differentiate the endothelial cells into the vascular endothelial cells. By using the scheme, the differentiation efficiency can exceed 99%, and differentiated cells have phenotypes and functions of vascular endothelial cells and do not express pluripotent related markers SSEA-4, TRA-1-60 and TRA-1-81.

The present invention is related to bispecific antigen binding molecules that specifically bind to Activin A and GDF8, and therapeutic and diagnostic methods of using those molecules.

A major obstacle in the field of biotherapeutics is the need for platform technologies that enable high bioavailability and long-term therapeutic exposure of biotherapies in localized disease. Traditional approaches result in problematic trade-offs, such as toxicity and off-target side effects. The present disclosure provides compounds comprising follistatin domain 1 (FSD1) of follistatin (FST), which can bind to biological structures, such as the extracellular matrix, via heparan sulfate without the undesired neutralizing effects on the activity of activin A, myostatin, and GDF11, as full-length follistatin does. The present invention relates to fusion or conjugated proteins, compositions thereof, constructs or vectors encoding them, their medical uses, and methods for biotherapeutics.

The invention provides a 3D culture method for promoting stem cells to be differentiated into cardiac lineage cells. According to the method, four-stage time sequence induction is adopted, wherein in the stage I, BMP4, Activin A and bFGF are used for efficiently inducing the cells into mesoderm in an insulin-free culture medium; in the stage II, DKK1 is used for inhibiting WNT signals to lock the heart pedigree, and VEGF165 is added in the early stage to start cardiac endothelial differentiation; in the stage III, metabolic support is provided for an insulin-containing culture medium, and bilineage maturation is deepened; in the IV stage, bFGF is added to support long-term survival and function maintenance of the cells, and the whole process is carried out in a 3D embryoid body. According to the invention, the cheap RPMI1640 basal culture medium is used for replacing an expensive commercial culture medium, the high-purity heart micro-tissue which can spontaneously beat and contains cardiac muscle and cardiac endothelial cells can be obtained within about 10 days, and an economical and efficient cell source is provided for heart disease research, drug screening and regenerative medicine.

The invention discloses a method for efficiently and directionally inducing IPS to be differentiated into pancreatic beta cells. According to the method, through staged signal regulation and strict cell screening, the directionality and the overall efficiency of differentiation are remarkably improved. The whole process pays attention to cell quality control from the initial stage, and a stable foundation is laid for subsequent differentiation by screening iPS cells with uniform morphology and high expression of pluripotent markers. Progressive signal molecule regulation is adopted in each stage, and an accurate differentiation path is formed from Activin A gradient adjustment during endoderm induction, synergistic effect of FGF10 and retinoic acid in pancreatic precursor cell differentiation and Wnt signal inhibition during endocrine precursor cell induction, so that the non-specific differentiation tendency is effectively reduced. Meanwhile, cell enrichment steps of key nodes, such as SOX17 positive cell screening in an endoderm stage and Ngn3 magnetic bead sorting of endocrine precursor cells, further improve the purity of a target cell population and avoid interference of parenchyma cells on subsequent function maturation.

The invention relates to a serum-free culture medium with limited chemical components for mesenchymal stem cells as well as a preparation method and application of the serum-free culture medium. The culture medium comprises a basic culture medium, growth factors and a carrier protein stabilizer, the growth factors comprise a proliferation promoting factor, an activating agent, a signal factor and nutrients; the activating agent comprises Wnt7a protein and LIF protein. According to the invention, Wnt7a, LIF, Noggin, Activin A and TGF-beta3 are combined together according to a specific concentration and proportion (especially Wnt7a and LIF) for the first time, and cooperate with other factors (FGF-2 and IGF-1) to construct a brand new signal network capable of simulating an in-vivo dry microenvironment.

The invention relates to application of folliclostatin in treatment of inflammatory bowel diseases, and belongs to the technical field of biological medicines. The invention provides application of folliclostatin FST in preparation of a medicine for treating acute inflammatory bowel disease. The invention relates to an application of folliclostatin FST in preparation of a medicine for treating acute inflammatory bowel disease by inhibiting myeloperoxidase. The invention relates to an application of folliclostatin FST in preparation of a medicine for treating chronic inflammatory bowel diseases. The invention relates to an application of folliclostatin FST in preparation of a medicine for treating chronic inflammatory bowel disease by improving mesenteric fat quality. The invention relates to an application of folliclostatin FST in preparation of drugs for treating inflammatory bowel diseases by blocking Th17 induction effect of activin A. The folliclostatin FST can be used for treating inflammatory bowel diseases. The invention discloses the treatment effect of FST, and discloses a new target spot of IBD treatment, namely an FST-activin A-Th17 axis, which has important clinical significance and transformation value.

The present invention belongs to, but is not limited to, the field of genetic engineering technology and discloses a Japanese eel Activin A recombinant protein, its expression method, and application. The Japanese eel Activin A recombinant protein comprises: the amino acid sequence of the Japanese eel Activin A mature peptide, a 6× histidine tag at the N-terminus, and a SUMO solubilizing polypeptide; its amino acid sequence is SEQ ID NO: 1, and the nucleotide sequence of the gene encoding the Japanese eel Activin A recombinant protein is SEQ ID NO: 3. The present invention constructs the prokaryotic expression vector pET-His-SUMO-ActivinA for Japanese eel Activin A for the first time, which can produce an Activin A recombinant protein with an amino acid sequence consistent with the Japanese eel Activin A mature peptide, which can be applied to the research on ovarian development regulation and artificial reproduction of Japanese eels.

Provided in the present invention are an siRNA for inhibiting the expression of the activin A receptor type 1C (ACVR1C) gene, and a conjugate thereof. The siRNA comprises a sense strand and an antisense strand. The antisense strand comprises at least 17 consecutive nucleotides that differ from nucleotide sequences set forth in SEQ ID NO: 1236-SEQ ID NO: 2470 by no more than 4 nucleotides. The antisense strand is 17-30 nucleotides in length; and the sense strand is 17-30 nucleotides in length, and is at least partially or completely complementary to the antisense strand. The siRNA, siRNA conjugate and pharmaceutical composition provided in the present invention exhibit good stability, great ACVR1C gene inhibitory activity, and satisfactory cytotoxicity and immunostimulatory activity.

The invention discloses a preparation method and application of autonomic ganglion organoid, and relates to the technical field of biology. The method comprises the following steps: 1) providing neural crest stem cells; 2) differentiating the neural crest stem cells into autonomic ganglion-like organs through the combined action of added external factors and internal factors; wherein the external factors comprise a bFGF (basic fibroblast growth factor), an IGF-1 (insulin-like growth factor), a BDNF (brain-derived neurotrophic factor), a GDNF (brain-derived neurotrophic factor), an NGF (nerve growth factor), an NT-3, an EGF (epidermal growth factor), Forskolin, a DAPT (diaminopropyltriethoxysilane), an insulin, a Transferrin, an Activin A and a BMP4 (bone morphogenetic protein 4); the addition of the intrinsic factors is that the following four transcription factors, namely Ascl1, Hand2, Phox2a and Phox2b, are overexpressed in the neural crest stem cells at the same time. The organoid prepared by the scheme contains various neurons similar to the autonomic ganglion in vivo, Schwann glial cells and satellite glial cells. The prepared autonomic ganglion organoid can be applied to research on development regulation of autonomic ganglions and occurrence and development mechanisms of various human diseases, development of therapeutic drugs and the like.

Provided herein are agonistic antibodies and / or antigen binding fragments thereof that bind to ALK1, and methods of using the same.

Provided herein are novel bispecific anti-myostatin and anti-Activin A antibody or antigen binding fragments thereof comprising: a first antibody or antigen binding fragments thereof that binds to myostatin; and a second antibody or antigen binding fragments thereof that binds to Activin A.

Provided herein are methods and compositions for obtaining hepatocytes. Provided herein is a kit or cell culture medium composition for inducing hepatocytes from pluripotent stem cells, the composition comprising the following inducers: (1) Activin A, (2) a modulator of the BMP signaling pathway, (3) a modulator of the FGF signaling pathway, (4) a modulator of the Wnt signaling pathway, (5) a growth factor, (6) a TGFβ receptor / ALK5 inhibitor. Also provided herein are methods for preparing hepatocytes by the kit or cell culture medium composition, hepatocytes obtained by the methods, artificial liver devices containing the hepatocytes and / or use of the hepatocytes for preparing artificial liver devices, and methods for large scale culture of hepatocytes.

The present invention relates to a combination therapy of an approved GLP-1 receptor agonist treatment and a microorganism transformed with a cell surface display vector operably linked with a gene encoding myostatin and activin A proteins for the treatment of muscle loss related to obesity. The microorganism may be formulated to include pharmaceutically viable excipients, such as antiadherents, binders, carriers, coatings, colorants, disintegrants, diluents, flavorings, glidants, lubricants, preservatives, sorbents, or vehicles.

The application belongs to the technical field of cell biology, and particularly relates to a feeder-free and serum-free bovine embryonic stem cell culture medium, a culture system and a culture method. The bovine embryonic stem cell culture medium comprises a conditioned medium and an additive. The additive is IWR-1 and activin A. The concentrations of IWR-1 and activin A in the conditioned medium are 2.5-5 muM and 20 ng / mL-25 ng / mL respectively. The culture system comprises the bovine embryonic stem cell culture medium, 0.1%-0.2% gelatin in mass concentration and a subculture medium. The 0.1%-0.2% gelatin in mass concentration is used to provide an attachment matrix for the bovine embryonic stem cell. The subculture medium is prepared by adding Y27632 to the bovine embryonic stem cell culture medium. The application reduces the cost of extracellular matrix, and the feeder-free bovine embryonic stem cell has high single cell subculture efficiency and is convenient for gene editing operation.

The present invention is related to bispecific antigen binding molecules that specifically bind to Activin A and GDF8, and therapeutic and diagnostic methods of using those molecules.

The present invention provides stabilized activin IIB receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the stabilized polypeptides and proteins. Compositions and methods for treating muscle-wasting diseases and metabolic disorders are also provided.

The invention relates to the technical field of cell culture, in particular to a method for induced culture of embryonic stem cells. The method comprises the following steps: resuscitating cryopreserved Balb / c mouse embryonic stem cells, culturing with a culture solution A containing leukemia inhibition factors, and continuously culturing with a culture solution B containing Activin A after passage; sequentially culturing in an HM culture medium added with specific cell factors, and cooperatively using a cell induction matrix prepared from various components such as hyaluronic acid, 3-aminophenylboronic acid, mono-ammonium glycyrrhizinate and the like. Through the synergistic effect of each culture step and each component in the cell induction matrix, the liver microenvironment is simulated, the cell growth factors are slowly released, and meanwhile, the anti-oxidation characteristic of quercetin is exerted, so that the induced differentiation efficiency of the embryonic stem cells is effectively improved.

The invention relates to a culture medium for inducing embryonic stem cells to differentiate into neural stem cells and an induction method. The culture medium is a basic culture medium added with the following concentration components: 1.5 mM to 2.5 mM of L-glutamine substitute, 0.9 * 1.2 * of non-essential amino acid, 0.8 mM to 1.5 mM of sodium pyruvate, 0.1 v / v% to 0.3 v / v% of beta-mercaptoethanol, 0.5 * 1 * of N2 additive, 0.5 * 1 * of B27 additive, 15 ng / mL to 25 ng / mL of bFGF, 15 ng / mL to 25 ng / mL of activin A, 2 mu M to 4 mu M of CHIR99021 and 1 mu M to 3 mu M of XAV939. When the culture medium is used for culturing the embryonic stem cells for a proper time, the embryonic stem cells can be effectively induced to a state which is more favorable for being differentiated into neural stem cells, and then the neural stem cell differentiation induction culture medium is used for continuous culture, so that the efficiency of differentiating the embryonic stem cells into the neural stem cells can be greatly improved; and the obtained neural stem cell expresses specific labeled proteins Nestin and Sox1 and has a garland structure, and the functional phenotype is stable.

The invention provides a composition, a cell culture medium and application of the cell culture medium in establishment of trophoblast stem cells in bovine hatching blastocysts, and belongs to the technical field of cell engineering. The invention provides a composition. The composition comprises activin A, CHIR99021 and a recombinant human leukemia inhibition factor. After the composition is adopted to culture hatched blastocysts, bovine trophoblast stem cells are obtained in vitro, trophoblast cell specific markers are highly expressed in mRNA and protein levels, and the bovine trophoblast stem cells can be stably cultured in vitro for a long time. The composition not only can further enrich the culture system of the bovine trophoblast stem cells, but also can expand understanding of the difference of signal pathways causing the blastocysts in different stages of the cattle.

Aspects of the disclosure relate to compositions and methods for treating fibrodysplasia ossificans progressiva (FOP) in a subject. In some aspects, the disclosure provides isolated nucleic acids, and vectors such as rAAV vectors, configured to express transgenes that inhibit (e.g., decrease) expression of an INHBA and / or inhibit (e.g., decrease) expression of an mutated ACVR1 gene and / or promote (e.g., increase) expression of wild-type ACVR1 protein in muscle cells, bone cells or connective tissues.

The application belongs to the technical field of medical diagnosis, and specifically discloses a diabetes mellitus combined with tuberculosis marker and application thereof. It is found for the first time that the transcription level and protein level of activin A receptor 2A (ACVR2A), angiostatin and chemokine ligand 14 (CXCL14) are inversely proportional to the severity of diabetes mellitus combined with tuberculosis, and can be used as a diabetes mellitus combined with tuberculosis marker to indirectly reflect whether the crowd is suffering from diabetes mellitus combined with tuberculosis and the development of the disease, so as to timely diagnose and treat. A new diabetes mellitus combined with tuberculosis detection kit can be prepared according to the three markers, and is applied to public medical treatment. The three markers can effectively improve the diagnosis efficiency of diabetes mellitus combined with tuberculosis, and have high sensitivity and strong specificity.