40 results about "Hepatocyte growth factor" patented technology

This invention discloses a fusion protein targeting the urokinase-type plasminogen activator receptor and its application in the field of anti-aging. The fusion protein is composed of a hepatocyte growth factor active domain and a humanized anti-uPAR single-domain antibody linked by a flexible linker peptide, and its specific amino acid sequence is SEQ ID NO:3. This fusion protein can specifically bind to uPAR, which is highly expressed on the surface of senescent cells, with intramolar affinity, achieving targeted delivery of the hepatocyte growth factor active domain. In vitro experiments have demonstrated that this protein can significantly reverse the aging phenotype of human fibroblasts, effectively reduce aging-related β-galactosidase activity, p16INK4a protein expression, and interleukin-6 secretion, and promote cell proliferation. In a rapidly aging mouse model, this protein can systematically improve age-related physiological functional decline. The fusion protein of this invention achieves specific targeting and efficient treatment of senescent cells, providing a new solution for the development of anti-aging drugs.

The present invention provides an agent for protecting and regenerating pancreatic beta cells in a mammal having diabetes, the agent containing a recombinant viral vector that expresses hepatocyte growth factor (HGF), wherein the agent is characterized by being administered in a dose of 1010-1012 virus particles (vp) / kg body weight, and by the virus vector including a nucleic acid that encodes HGF downstream of a promoter having transcription activity capable of yielding a therapeutically effective HGF level in the blood at said dose.

The invention relates to the technical field of biological medicines, in particular to a preparation method of a stem cell factor composition for promoting scalp hair follicle regeneration. The method comprises the following steps: performing high-low oxygen cycle pre-stimulation and stepped hypoxia induction on umbilical cord mesenchymal stem cells, monitoring secretion kinetics of vascular endothelial growth factors (VEGF), hepatocyte growth factors (HGF), keratinocyte growth factors (KGF) and fibroblast growth factors 2 (FGF2) in real time, and determining the optimal collection time; performing ultrafiltration on the supernate to obtain a primary concentrated solution, optimizing the molecular weight cutoff based on the bioactivity retention rate after freezing and thawing, and concentrating to obtain a stem cell factor concentrated solution; the stem cell factor composition is obtained by combining the stem cell factor with a compound nutrition preparation, verifying in-vitro hair follicle cell proliferation / migration activity, dynamically adjusting the nutrition proportion according to the relative efficiency ratio and optimizing. According to the invention, intelligent preparation of the stem cell factor composition with multi-factor synergistic secretion, controllable process, stable activity and adjustable functions is realized.

The invention provides an injection for inducing mesenchymal stem cells. The induced mesenchymal stem cell injection is prepared from induced mesenchymal stem cells modified by hepatocyte growth factors with the cell density being 1.0 * 10 < 5 >-2.0 * 10 < 7 > / ml, HSA with the mass concentration being 0.25%-6%, DMSO with the mass concentration being 5%-10%, glucose with the mass concentration being larger than 0 and smaller than 1%, compound amino acid with the concentration being 0.5-5 mg / mL and the balance compound electrolyte injection. And the induced mesenchymal stem cell injection has a pH value of 6.8 to 7.5. The induced mesenchymal stem cell injection is good in homogeneity, small in batch difference and stable in curative effect, can effectively promote damaged tissue repair, can be directly intravenously injected after cryopreservation and recovery, keeps high cell viability and drug activity, achieves an excellent treatment effect, has good room-temperature stability, is convenient to transport and store, and is suitable for clinical application. The method is suitable for different clinical application occasions, and the clinical application range of the mesenchymal stem cells is expanded.

The invention relates to the technical field of regenerative medicine application, in particular to a serum-free induction culture medium with definite components for promoting adipose tissue-derived cells to be differentiated into dermal papilla cells, an induction method and application. The invention relates to a method for promoting adipose tissue-derived cells to differentiate into dermal papilla cells, which is characterized in that the adipose tissue-derived cells are induced and cultured by using a serum-free induction culture medium, so that the adipose tissue-derived cells are differentiated into the dermal papilla cells. The formula of the serum-free induction culture medium comprises hepatocyte growth factors, hydrocortisone, bone morphogenetic protein 2, BIO and basic fibroblast growth factors. Based on the differentiation potential of adipose tissue-derived mesenchymal cells and the function maintenance mechanism of dermal papilla cells, a serum-free induction system with definite components is constructed, and directional differentiation is realized. According to the technical scheme, the technical problem that a method for inducing the adipose-derived mesenchymal cells to be directionally differentiated into the dermal papilla cells with the effective hair follicle regulation function is lacked in the prior art can be solved, and the method has ideal application and popularization potential.

The invention relates to the technical field of medicines, in particular to application of allogenic liver precursor cells in preparation of a medicine for treating liver cirrhosis, and the liver cirrhosis is decompensated liver cirrhosis. The allogenic liver precursor cells degrade extracellular matrix, fibroblast growth factor (FGF) and hepatocyte growth factor (HGF) through paracrine MMPs to promote hepatocyte regeneration and repair and the like, so that the liver cirrhosis is relieved and improved.

The invention discloses a linear poly (beta-amino ester) compound loaded with hepatocyte growth factors as well as a preparation method and application of the linear poly (beta-amino ester) compound, and belongs to the technical field of biological medicines. The compound is obtained by self-assembly of linear poly beta-amino ester DD90-C12-DMEN and HGF mRNA in a buffer solution, the compound is suitable for aerosol inhalation delivery, higher mRNA transfection efficiency is obtained in lung-related epithelial / stromal cells, macrophages and other cells difficult to transfect, and particularly, the compound shows remarkable transfection advantages on the macrophages.

The invention belongs to the technical field of medicines, and particularly relates to application of a pigment epithelium-derived factor (PEDF) in synergistically enhancing a hepatocyte growth factor (HGF) in resisting pulmonary arterial hypertension (PH). Research finds that the HGF can improve pulmonary artery remodeling in PH, but can aggravate vascular leakage through a VEGF / VEGFR2 pathway. The PEDF can be combined with VEGFR2 (vascular endothelial growth factor receptor 2) to inhibit VEGF-induced endothelial cell activation and permeability increase. Meanwhile, a specific region of the PEDF is combined with the VEGFR2 under the action of a hydrogen bond and the like, and a derivative peptide fragment of the PEDF can block a VEGF / VEGFR2 signal. Compared with single HGF, cotransfection of the PEDF and the HGF can better inhibit angiogenesis and leakage and delay PH progress. Researches prove that the PEDF counteracts the leakage promoting side effect of the HGF through specific binding with the VEGFR2, and a theoretical basis is provided for developing a PH treatment strategy of the HGF combined with the PEDF derived peptide.

Provided herein are genetically modified cells such as pluripotent stem cells and mesenchymal stem cells and methods of making the same. The gene editing strategies of the present disclosure enable high expression of transgenes in genetically modified cells.

This invention relates to the field of biomedical materials technology, providing a heparinized dual-growth factor recellularized adipose tissue decellularized scaffold material, its preparation method, and its applications. The preparation method includes: decellularizing adipose tissue to obtain adipose tissue decellularized scaffold; heparinizing the scaffold to obtain a heparinized adipose tissue decellularized scaffold; loading hepatocyte growth factor and vascular endothelial cell growth factor onto the scaffold to obtain a heparinized dual-growth factor adipose tissue decellularized scaffold; seeding induced pluripotent stem cell-derived hepatocytes onto the scaffold, and culturing to obtain a heparinized dual-growth factor recellularized adipose tissue decellularized scaffold (RAT). This invention uses rat inguinal adipose tissue to prepare RAT material, which is low-cost, readily available, has a simple preparation process, and is easy to scale up. The RAT material of this invention can achieve liver tissue damage repair and hepatocyte regeneration, providing a new treatment strategy for acute liver failure.

The present invention relates to an adeno-associated virus (AAV) vector optimized for intrathecal administration into which a hepatocyte growth factor gene is introduced. The AAV vector of the present invention and AAV particles produced through the vector have excellent productivity of AAV particles comprising a hepatocyte growth factor gene, and when administered intrathecally to a mammal, the expression efficiency of hepatocyte growth factor is also very high. Therefore, the AAV vector of the present invention and the AAV particles induce the expression of hepatocyte growth factor protein when administered intrathecally, and thus can be effectively used in the prevention or treatment of related diseases.

The application discloses a kind of serum-free epidermal melanocyte culture medium and its application, method includes by dissolving adenine, hepatocyte growth factor (HGF), glutamine, retinoic acid, vitamin E, nicotinic acid, sodium selenite, sodium hyaluronate and recombination human type XVII collagen are configured into initial culture medium;Preparation of melanocyte stimulating hormone, endothelin-3, transferrin, triiodothyronine, cholesterol, neuroregulin 1 (NRG1), 3-isobutyl-1-methyl purine (IBMX), dibutyryl cyclic adenosine monophosphate (db-cAMP), cholera toxin, hydrocortisone and recombination human insulin mother liquor;Step three: according to culture and concentration, a certain amount of mother liquor of step two is added to initial culture medium.The culture medium can effectively promote human epidermal melanocyte proliferation, melanin accumulation and help to promote human umbilical cord mesenchymal stem cells into human epidermal melanocyte, provide key advantage for obtaining functional melanocyte with high activity and therapeutic potential.

Disclosed is an in vitro method for assessing whether a human subject has periodontitis. The method comprises detecting, in a sample of saliva from said subject, the concentrations of the proteins Hepatocyte Growth Factor (HGF) and Matrix Metalloproteinase 8 (MMP-8). Based on the concentrations determined, and adding age, and possibly other demographic markers such as sex and / or BMI, a testing value reflecting the joint concentrations is determined for said proteins, in combination with one or more demographic markers. The testing value is compared with a threshold value. The threshold reflects in the same manner the joint concentrations and the age, and possibly other demographic markers, as associated with periodontitis and may be seen as an upper limit of testing values as seen in a population of subjects without periodontitis. Thereby a testing value at or above the threshold value is indicative for periodontitis in said subject.

The invention relates to a liver cancer organoid culture medium and application thereof, and belongs to the technical field of medicines. The liver cancer organ-like culture medium disclosed by the invention is prepared from the following components: AdvDMEM F12, HEPES, GlutaMAX, B27, EGF (Epidermal Growth Factor), N-acetyl-L-cysteine, gastrin, HGF (Hepatocyte Growth Factor), FGF-10 (Fibroblast Growth Factor), A83-01, nicotinamide, N2, an adenylate cyclase activator, a three-antibody antibiotic, R-spondin1, Wnt-3a, Y-2763, Noggin, oncostatin M and FGF-23. The culture medium is rich in nutrition and reasonable in component; the liver cancer organoid cell spheres cultured by using the culture medium can stably grow for a long time, continuously amplify and repeatedly cryopreserve. When the culture medium is used for preparing the liver cancer organ model, a foundation is laid for knowing the pathogenesis of liver cancer and screening drugs.

The invention discloses a culture medium, a culture method and application of mouse hepatic sinus vascular endothelial cells. Belongs to the technical field of cell culture. Components of the culture medium are optimized, in the aspect of growth factors, conventional VEGF / bFGF combination is broken through, liver cell growth factors and platelet-derived growth factors are creatively compounded with the growth factors, cell proliferation is driven, and liver-derived specific phenotypes and functional integrity of LSEC are maintained. An anti-oxidation system composed of N-acetylcysteine, ascorbic acid, alpha-tocopherol and riboflavin is constructed, active oxygen is synergistically removed through multiple mechanisms, and the activity and stability of cells in long-term culture are improved. Sodium pyruvate is additionally supplemented as an energy substrate, and taurine, glycine and other specific amino acids simulating the intrahepatic microenvironment provide energy and nutritional support for cell proliferation, and promote function maintenance. The efficient and stable in-vitro amplification and function maintenance of the LSEC are realized, and a solid foundation is laid for constructing a high-fidelity LSEC model.

The present application relates to the technical field of regenerative medicine application, and particularly relates to a serum-free induction medium with clear components for promoting differentiation of adipose-derived mesenchymal cells into dermal papilla cells, and an induction method and application. A method for promoting differentiation of adipose-derived mesenchymal cells into dermal papilla cells, which is to use a serum-free induction medium to induce culture of adipose-derived mesenchymal cells, so that the adipose-derived mesenchymal cells are differentiated into dermal papilla cells. The formula of the serum-free induction medium comprises hepatocyte growth factor, hydrocortisone, bone morphogenetic protein 2, BIO, and basic fibroblast growth factor. The present application is based on the differentiation potential of adipose-derived mesenchymal cells and the mechanism of maintaining the function of dermal papilla cells, and constructs a serum-free induction system with clear components to realize directional differentiation. The technical scheme can solve the technical problem that there is no method for inducing directional differentiation of adipose-derived mesenchymal cells into dermal papilla cells with effective hair follicle regulation function in the prior art, and has ideal application and popularization potential.

The invention relates to a molecular marker for diagnosis, prognosis evaluation and treatment of cardiac fibrosis, and belongs to the technical field of biological medicines. The invention provides a molecular marker capable of diagnosing cardiac fibrosis, evaluating the severity of cardiac fibrosis, evaluating the prognosis of cardiovascular diseases accompanied with cardiac fibrosis or evaluating the prognosis of acute myocardial infarction. The molecular marker comprises a hepatocyte growth factor. Research finds that the HGF is remarkably increased in plasma of a patient with cardiac fibrosis, and the plasma HGF level of a patient with aortic valve stenosis is also remarkably increased before an operation, so that the HGF can be used for diagnosing cardiac fibrosis and evaluating the severity of cardiac fibrosis. Researches find that timely transient increase of the HGF in plasma of a patient with acute myocardial infarction is significantly related to good prognosis, and continuous low-level increase, continuous high-level increase, recurrence and delayed increase of the HGF are significantly related to poor prognosis, so that the HGF can be used for evaluating prognosis of acute myocardial infarction.

The invention belongs to the technical field of chemical material engineering, and particularly relates to a hydrogel coating capable of promoting tissue repair and regeneration, which is characterized by being mainly prepared from the following materials: biomolecules mixed in a hydrogel material, and a water-retaining agent, the biomolecules comprise a combination of more than one of the following components: bone morphogenetic protein 7, hepatocyte growth factors, transforming growth factors-beta and retinoic acid. The hydrogel is combined with the carboxylated chitosan hydrogel coating, the bone morphogenetic protein 7 (BMP7), the hepatocyte growth factor (HGF), the transforming growth factor beta (TGF-beta) and the retinoic acid, so that the hydrogel has a synergistic effect of promoting the regeneration and repair of postoperative tissues, and can be applied to the drainage tube to improve the mechanical property and the structural stability and improve the treatment effect.

This invention relates to a method for evaluating the wound-healing efficacy of mesenchymal stem cell (MSC) populations. Furthermore, this invention relates to a method for selecting MSCs for generating stem cell populations under cGMP conditions, and a method for selecting MSC populations for generating stem cell populations for subsequent drug administration. Additionally, this invention relates to a method for selecting MSC populations for generating a master cell bank, and a method for identifying tissues suitable as starting materials for generating MSC populations for drug use. The method includes measuring the levels of at least two proteins selected from angiopoietin-1 (Ang-1), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) secreted by MSCs into the culture medium.

This disclosure relates to a method for establishing a HepaRG-based differentiated liver 3D microsphere model and its applications. Specifically, this disclosure provides a chemically defined differentiation medium formulation that does not require DMSO and contains hepatocyte growth factor, dexamethasone, and hepatoprotectin M. Using this medium, HepaRG cells can be efficiently induced to form compact, long-lived 3D microspheres in ultra-low adsorption 96-well plates or in conjunction with high-throughput 3D printing technology. After differentiation and maturation, the model can stably express hepatocyte markers, key drug-metabolizing enzymes, and nuclear receptors at high levels. The liver 3D microsphere model established by this disclosure can effectively simulate hepatocyte function in vivo and is suitable for high-throughput drug hepatotoxicity screening. The results show a high degree of consistency with clinical hepatotoxicity data, and it has important application value in the field of drug safety evaluation.

Provided is a computer-implemented method for selecting a subject at risk for developing Crohn's disease, including a trained logistic regression model classifying a subject as at risk for developing Crohn's disease based on blood levels of C-X-C motif chemokine ligand (9), transforming growth factor α, hepatocyte growth factor, C-C motif chemokine ligand (11), matrix metalloproteinase (10), matrix metalloproteinase (1), C-X-C motif chemokine ligand (11), C-C motif chemokine ligand (19), C-C motif chemokine ligand (23), and tumor necrosis factor β.

The present disclosure relates to activated hepatocyte growth factor (HGF) and compositions and methods for producing the same, including, for example, cells and / or populations of cells engineered to co-express hepsin and HGF. In some embodiments, it includes cell(s) comprising one or more polynucleotide sequence) s) encoding a hepatocyte growth factor (HGF) polypeptide or biologically active variant thereof operably linked to an exogenous promoter; and one or more polynucleotide sequence) s) encoding a hepsin polypeptide or enzymatically active variant thereof operably linked to an exogenous promoter.

This invention discloses a highly active duck embryo liver primary cell and its low-cost preparation method and applications. The preparation method includes: obtaining and pretreatment of duck embryo liver tissue, separation by complex enzyme digestion, preparation of cell suspension, primary cell culture, and maintenance of cell viability. The core of this method lies in the gentle digestion using a complex digestion solution composed of collagenase I, trypsin, and DNase I in specific weight ratios, followed by culture in a well-defined, non-commercial growth factor-free complete culture medium. This complete culture medium contains synergistic components such as DMEM / F12, fetal bovine serum, epidermal growth factor, hepatocyte growth factor, and an insulin-transferrin-selenium mixture. The duck embryo liver primary cells prepared by this invention exhibit high yield, high viability, and excellent liver-specific function, and can maintain their activity and function well after passage and cryopreservation.

The present invention relates to an adeno-associated virus (AAV) vector optimized for intrathecal administration into which a hepatocyte growth factor gene is introduced. The AAV vector of the present invention and AAV particles produced through the vector have excellent productivity of AAV particles comprising a hepatocyte growth factor gene, and when administered intrathecally to a mammal, the expression efficiency of hepatocyte growth factor is also very high. Therefore, the AAV vector of the present invention and the AAV particles induce the expression of hepatocyte growth factor protein when administered intrathecally, and thus can be effectively used in the prevention or treatment of related diseases.

The application provides a method for long-term in-vitro culture and expansion of primary hepatocytes and application thereof. The method for in-vitro culture and expansion of primary hepatocytes comprises using a culture medium containing interleukin-22 (IL-22), combined with hepatocyte growth factor (HGF) and / or epidermal growth factor (EGF) to induce primary hepatocytes to prepare proliferative liver precursor cells. The application combines interleukin-22 (IL-22), hepatocyte growth factor (HGF) and / or epidermal growth factor (EGF) to induce in-vitro mass expansion of primary hepatocytes, and through the method, mature-like hepatocytes with a gene expression profile extremely similar to that of primary hepatocytes and perfect functions can be obtained, and the hepatocytes expanded by the method have good in-vivo therapeutic effects.

The present application relates to a kind of preparation for increasing the excretion capacity of multifunctional stem cell exosome and its application, belong to cell culture technical field.The preparation is composed of culture medium component I and culture medium component II, component I contains transforming growth factor-beta, hepatocyte growth factor etc., for activating stem cell;Component II contains N-acetyl cysteine, vitamin C etc., promote exosome secretion under low oxygen condition.By using two components in a specific order, the exosome secretion amount and biological activity of umbilical cord mesenchymal stem cells can be significantly improved.Compared with the traditional method, the exosome secretion amount treated by the method of the present application is increased by tens of times, and its ability to promote skin fibroblast proliferation and migration is significantly enhanced, so it has important application value in the field of skin repair, tissue regeneration etc..

The application relates to the technical field of biological medicine, and particularly provides a truncated mutant of chicken hepatocyte growth factor and application thereof in preventing and treating liver-related diseases. A nucleic acid molecule constructed based on the truncated mutant of the chicken hepatocyte growth factor and taking E. coli as an expression vector not only realizes efficient expression of the truncated mutant of the chicken hepatocyte growth factor, lays a foundation for industrial application of the truncated mutant of the chicken hepatocyte growth factor, but also has significant biological activity.

The invention discloses a culture medium and a culture method for amplifying adult kidney stem cells of mice, and relates to the technical field of stem cell culture. Comprising the following components: a fibroblast growth factor, interleukin-6, an insulin-like growth factor-1, a hepatocyte growth factor, a platelet-derived growth factor, a vascular endothelial growth factor, ascorbic acid, insulin, a growth hormone, hydrocortisone, Y-27632, CHIR99021, bovine serum albumin, linoleic acid, linolenic acid, 1-20 [mu] g / mL of alanine, 1-20 [mu] g / mL of asparagine, 1-20 [mu] g / mL of glutamic acid and the balance of water. The invention relates to the field of medicine, in particular to a medicine for preventing and treating diseases. The culture medium provided by the invention can be used for continuously and stably culturing more than 25 generations of adult kidney stem cells of mice, and a more stable kidney stem cell long-term in-vitro amplification system is established compared with an international existing culture system.

Provided are genetically modified non-human animals that are immunodeficient and optionally comprise xenotransplanted hepatocytes such as human hepatocytes, wherein the genetically modified non-human animal and / or the transplanted hepatocytes are modified to restore, activate, or increase interleukin-6 (IL-6) / interleukin-6 receptor (IL-6R) signaling pathway activity or interleukin-6 receptor subunit beta (GP130) signaling pathway activity and to restore, activate, or increase hepatocyte growth factor (HGF) / hepatocyte growth factor receptor (MET) signaling pathway activity in the transplanted hepatocytes. Also provided are methods of measuring or assessing the activity of human-liver-targeting reagents in such non-human animals and methods of making animals with a humanized liver (e.g., with reduced steatosis). Also provided are genetically modified, immunodeficient, non-human animals comprising a humanized HGF gene and optionally a humanized IL6 gene and methods of using and making such animals. Also provided are methods of increasing or accelerating engraftment of xenotransplanted hepatocytes in non-human animals.

The invention discloses a mesenchymal stem cell suitable for osteoarthritis diseases and cultured by adopting an optimized medicine combination, and belongs to the technical field of stem cells. The technical problems to be solved are that in the existing mesenchymal stem cell culture process, stemness loss, differentiation potential weakening, multiplication capacity reduction and the like are easily caused by increase of culture generations. According to the key point of the technical scheme, the pharmaceutical composition is provided and comprises betamethasone dipropionate, betamethasone sodium phosphate, interleukin-10 (IL-10) and a hepatocyte growth factor (HGF), by adding the composition into a mesenchymal stem cell culture medium, the technical problems of stemness loss, differentiation potential weakening, multiplication capacity reduction and the like caused by increase of culture generations can be effectively solved.