29 results about "Activin a" patented technology

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 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 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.

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 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 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 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.

To provide treatment of fibrodysplasia ossificans progressiva.SOLUTION: Methods for treating fibrodysplasia ossificans progressiva (FOP) in a human subject are provided. Such methods involve administering to a subject having FOP a therapeutically effective amount of an activin A antagonist, such as an antibody to activin A. The present disclosure provides methods of treating fibrodysplasia ossificans progressiva (FOP) comprising administering to a subject having FOP a therapeutically effective amount of an activin A antagonist. In particular, the inventors of the present application have surprisingly discovered only after conducting a Phase II clinical trial in humans that treating FOP subjects with an activin A antagonist dramatically reduces and / or prevents the progression of new heterotopic ossification (HO) bone growth and reduces the average rate of lesion growth and mineralization.SELECTED DRAWING: None

The invention relates to the technical field of islet cell culture, and discloses a method for inducing mesenchymal stem cells to be differentiated into islet-like cells and application of the islet-like cells, and the method comprises the following steps: inoculating the mesenchymal stem cells into an umbilical cord-based tissue cell culture medium A for adherent multiplication culture; preparing the amplified mesenchymal stem cells into a cell suspension, and aggregating the cells into balls through centrifugation or limited culture; carrying out induced culture on the mesenchymal stem cell spheres by using a culture medium B; carrying out induced culture on the started cell balls by using a culture medium C; and carrying out induced culture on the differentiated cell balls by using a culture medium D to obtain the islet-like cells. Mesenchymal stem cells are prepared into cell spheres to enhance the intercellular interaction, and a culture medium B containing activin A and all-transretinoic acid, a culture medium C containing high glucose and nicotinamide and a culture medium D containing trichostatin A and Exendin-4 are used for staged induction to obtain the islet-like cells with the insulin secretion function.

The application discloses a nerve graft, a preparation method and application, and relates to a nerve conduit with an inner wall loaded with activin A-containing microspheres. The nerve graft provided by the application is a growth factor delivery system with excellent performance and controllable release kinetics, can realize efficient repair of a nerve defect of a rat, and the preparation method of the nerve graft is convenient and easy to operate, thereby laying a reliable technical foundation for development of a next-generation intelligent nerve graft.

The invention relates to the technical field of regenerative medicine and cell therapy, in particular to a culture medium for inducing mesenchymal cells to differentiate into insulin-secreting cells and application of the culture medium. By accurately regulating and controlling the oxidation-reduction state of NAD < + > / NADH in cells, the composition proportion of exogenous fatty acid, the dynamic supply concentration of glucose and the anti-oxidative stress level, the differentiation efficiency is remarkably improved, the induction period is shortened, and the method is suitable for industrial production on the premise of not depending on recombinant protein induction factors such as Activin A and Wnt3a. And a mature beta-like cell with stable glucose stimulus dependent insulin secretion (GSIS) capability is obtained. The kit is especially suitable for human adipose tissue-derived mesenchymal stem cells, and can be used as an independent kit product for preclinical research and drug screening of diabetes cell replacement therapy.

The invention relates to the technical field of regenerative medicine and cell therapy, in particular to a method for inducing mesenchymal stem cells to differentiate into insulin-secreting cells and application of the method. According to the method, a culture system is regulated and controlled by stages, the glucose concentration is respectively regulated in different induction stages, an NAD + precursor substance, a fatty acid composition and an antioxidant factor are added, and a three-dimensional microcarrier culture mode is combined, so that the cell metabolism state, the oxidation-reduction balance and the space structure are dynamically regulated and controlled. Under the condition of not depending on recombinant protein inducing factors such as Activin A and Wnt3a, the efficient directional differentiation of the mesenchymal stem cells to the insulin-secreting cells is realized. By adopting the method disclosed by the invention, the differentiation efficiency can be improved, the induction period can be shortened, the mature beta-like cells with a stable glucose stimulation dependent insulin secretion function can be obtained, and the method is suitable for induced differentiation and related research application of the human adipose-derived mesenchymal stem cells.

The present invention provides novel pharmaceutical formulations comprising antibodies that specifically bind to human activin A. In addition to the anti-activin A antibody, the formulations may contain a histidine buffer, an organic cosolvent, and a thermal stabilizer. The pharmaceutical formulations of the present invention exhibit a surprising degree of antibody stability after months of storage and after being subjected to thermal and other physical stresses.

This invention provides an immunomodulatory factor, its preparation method, and its application. The immunomodulatory factor includes: Eotaxin-2, I-309, IL-12p40, IL-12p70, MIG, MIP-1a, TNF-α, AR, BDNF, bFGF, EGF-R, EG-VEGF, IGFBP-6, VEGF, NAP-2, PF4, Activin A, ANG-1, DAN, Follistatin, Galectin-7, ICAM-2, etc. The immunomodulatory factor can be used to prepare immunomodulators, cancer intervention agents, etc., and is of great significance for research on the mechanisms by which thymic mitochondria regulate anti-tumor immunity, including influencing immune cell metabolism, signal transduction, apoptosis, and immune escape.

This disclosure provides myostatin and activin A peptide immunogen constructs, compositions and methods for their use in, for example, maintaining and improving muscle physiology (e.g., increasing muscle mass, strength, function, tone or endurance), preventing and treating muscular or musculoskeletal injury, preventing and treating a disorder associated with muscle loss or insufficient muscle growth, and / or preventing and treating muscle wasting diseases.

The invention discloses an application of activin A in preparation of a nerve regeneration medicine. The invention proposes and verifies that the activin A can promote the repair and regeneration of nerve injury through the synergistic regulation of Schwann cells and neurons for the first time, and provides a new direction for the treatment of diseases caused by nerve injury.

To provide a method for producing retinal pigment epithelial cells.SOLUTION: A method of producing retinal pigment epithelium (RPE) cells, comprising the steps of: (a) culturing a cell population of undifferentiated human pluripotent stem cells on an adherent surface selected from the group consisting of laminin, fibronectin, vitronectin, collagen I and collagen IV in a medium comprising nicotinamide as a differentiation-inducing agent and lacking activin A under feeder cell-free conditions to obtain differentiated cells; (b) culturing the differentiated cells on the adherent surface in a medium comprising nicotinamide and one or more members of the TGF β superfamily selected from the group consisting of TGF β 1, TGF β 3, and activin A to obtain RPE cells, wherein at least 50% of the cells in the population of cells are Oct4 + TRA-1-60 +.SELECTED DRAWING: Figure 1

The invention discloses a serum-free culture medium with definite chemical components for human umbilical cord mesenchymal stem cells, and belongs to the technical field of cell culture. The serum-free culture medium comprises a human umbilical cord mesenchymal stem cell basic culture medium and an additive, wherein the additive is prepared from Activin A, GDNF, R-spondin 2, SAG, SC79, human recombinant transferrin, vitamin C, human recombinant insulin and beta-sodium glycerophosphate. The cell culture auxiliary factors in the additive are added to replace serum to be used in a complete culture medium, so that the problems of unstable culture medium batch, easiness in pathogen pollution, high cost and the like caused by undefined serum chemical components are solved. Meanwhile, by adopting the serum-free culture medium disclosed by the invention, the proliferation efficiency can be improved and the cell activity can be better maintained in in-vitro proliferation.

The present invention provides compositions and methods related to Activin A variants. In particular, the present disclosure provides Activin A variants which have modulated receptor binding and / or receptor activation as compared to wild-type Activin A.

The application discloses a culture method of sheep primed-state stem cells, a culture medium used in the culture method and application of the culture method. The application belongs to the technical field of biotechnology and particularly relates to a culture method of sheep primed-state stem cells, a culture medium used in the culture method and application of the culture method. The composition for culturing sheep primed-state pluripotent stem cells contains an N2B27 basic culture medium, cytokines and small molecules. The cytokines and the small molecules contain human Activin A, recombinant human FGF2 and IWR1. The addition concentration of the human Activin A is 25 ng / mL; the addition concentration of the recombinant human FGF2 is 12.5 ng / mL; and the addition concentration of the IWR1 is 5 muM. The culture medium prepared by using the above composition can obtain stable sheep primed-state pluripotent stem cells, and can be applied in construction of a sheep gene editing model animal.