51 results about "Transdifferentiation" patented technology

The current disclosure is centered on the hypothesis that a better understanding of the neuroendocrine transdifferentiation (NEtD) process will provide therapeutic targets for inhibiting this transition and thus improving standard of care therapies. Accordingly, the current disclosure provides for a method for treating cancer in a subject, the method comprising administering an inhibitor of a gene, wherein the gene comprises one or more of tenascin C (TNC), advillin (AVIL), S100A7, PPARG, LOX lysyl oxidase, KLF5, APOBEC2, FOSL1, FOXM1, hedgehog, RELA, p65, IKK complex, JAK, STAT, TFAP4, geminin, OCA-1, OCA-2, Nf-kB, Nf-kB family and associated regulators, angiogenesis regulators such as BMX kinase, TEK kinase, periostin (POSTN), and VEGF family, stress genes, such as the JUN / FOS family, a gene from the S100 family, and cell state regulators such as ASCL1, POU2F3, NEUROD1, ASCL2, and YAP1.

The present invention provides a use of an Lck / Fyn-mediated STAT3 activation pathway as a target in the preparation or screening of a product. The product blocks the Lck / Fyn-mediated STAT3 activation pathway, inhibits differentiation of Th17 cells, and promotes transdifferentiation of the Th17 cells into Treg cells, thereby preventing or treating a Th17 cell-related immune disease. On the basis of the target, the present invention provides a use of an Lck / Fyn-mediated STAT3 activation blocker in the preparation of a product. The blocker is selected from an Lck / Fyn kinase inhibitor or a substance that specifically inhibits correct binding of Lck / Fyn and STAT3. The present invention provides a use of one or more biomaterials in the preparation of a product for preventing or treating the Th17 cell-related immune disease. The present invention also provides a drug for preventing or treating the Th17 cell-related immune disease and a treatment method thereof. Blocking Lck / Fyn-mediated STAT3 phosphorylation can be applied to the treatment of the Th17 cell-related immune disease or improvement of the capability to prevent an immune disease caused by the Th17 cells.

Provided are compositions of a system and methods of use thereof to transdifferentiate non-dermal papilla (DP) cells into induced dermal papilla cells (iDPCs) and to subsequent use of these cells in the treatment of hair loss.

A method of direct transdifferentiation of somatic cells into other somatic cells may be convenient and still have good reproducibility, excellent production efficiency, and short performed time. Methods for direct transdifferentiation of somatic cells into other somatic cells may include: (a) introducing a GLIS family gene, a mutated GLIS family gene or a gene product thereof into somatic cells; and (b) culturing the gene-introduced somatic cells in a culture medium containing a component that induces differentiation of the somatic cells or precursor cells of the somatic cells into other somatic cells.

The invention provides a method for inducing transdifferentiation of somatic cells into mammary epithelial cells by using an exosome for inducing mammary epithelial cells. The method is efficient, safe and high in specificity. The somatic cells are induced to be transdifferentiated into the mammary epithelial cells by inducing the mammary epithelial cell exosome, so that a new cell source and a new technical means are provided for repairing and regenerating mammary tissues and treating related diseases.

The invention belongs to the technical field of biomedicine, and particularly discloses an endowed mesenchymal stem cell, an endowed mesenchymal stem cell composition and application of the endowed mesenchymal stem cell composition to preparation of a medicine for treating organ insufficiency, and the endowed mesenchymal stem cell is obtained by treating human mesenchymal stem cells with ingenol HEP14. The energizing mesenchymal stem cell composition comprises energizing mesenchymal stem cells and HEP14 / PLGA microspheres which are prepared by adopting a polylactic acid-glycolic acid copolymer (PLGA) as a carrier and have high HEP14 loading capacity and long-acting HEP14 slow release. The energized mesenchymal stem cell has the effects of enhancing the survival activity and dryness of the mesenchymal stem cell, resisting tissue fibrosis, promoting tissue angiogenesis, and promoting tissue regeneration and functional recovery; the endowed mesenchymal stem cells and the HEP14 / PLGA microspheres are used in a combined manner, and the retention and transdifferentiation effects of the endowed mesenchymal stem cells in tissues are enhanced, so that the functions of the endowed mesenchymal stem cells and the application of the endowed mesenchymal stem cells in the field of regenerative medicine are further enhanced.

An extracellular vesicle based therapeutic compound for treating tumors and cancers. The extracellular vesicle based therapeutics use exosomes that are transdifferentiation-derived induced neural stem cells (Exo-iNSCs) that produce an extracellular vesicle having a tumoricidal gene product or an anti-cancer molecule withing the extracellular vesicle. The therapeutic agent is present in a lumen of the extracellular vesicle or is distributed across a membrane surface of the extracellular vesicle. Methods of using the extracellular vesicle based therapeutic compounds are effective in treating tumors and cancers.

The invention belongs to the technical field of biology, and discloses a serum-free culture medium and application thereof in obtaining nerve cells through embryo fibroblast transdifferentiation. The serum-free culture medium consists of a basic culture medium, a protein additive and cell culture auxiliary components, the protein additive consists of transferrin, a leukemia inhibition factor and a basic fibroblast growth factor; the final concentration of the transferrin is 5 ng / mL-30 ng / mL, the final concentration of the leukemia inhibition factor is 50 ng / mL-150 ng / mL, and the final concentration of the basic fibroblast growth factor is 10 ng / mL-25 ng / mL. The serum-free culture medium can promote the conversion speed of transdifferentiation of fibroblasts into nerve cells, can significantly improve the transdifferentiation efficiency, and can improve the cell survival rate of transdifferentiation of mouse embryo fibroblasts into nerve cells.

The present application belongs to the field of biomedical technology, and particularly relates to a cell-derived extracellular matrix and a preparation method and application of a cell culture plate coated with the cell-derived extracellular matrix. The present application cultures human astrocytes in a cell culture plate, and makes the human astrocytes secrete extracellular matrix. After the human astrocytes are added into a cell lysate for cell removal treatment, nucleic acid fragmentation treatment is performed to obtain the cell-derived extracellular matrix. The present application has relatively simple operation, short time period, and can realize batch production of extracellular matrix without external virus carrying and stable components. The obtained cell-derived extracellular matrix is resistant to storage, has good stability, is highly similar to a natural brain environment when coated on a cell culture plate, has good biocompatibility with cells, can be applied to tissue repair and regeneration as an ideal biomedical material, can regulate the progress and efficiency of human dermal fibroblast HDF transdifferentiation into neurons, and can obtain in-vitro survival neurons.

The invention belongs to the technical field of biology, and particularly discloses application of Olig2 in transdifferentiation of astrocytes into functional neurons, and the application provided by the invention realizes overexpression of neurogenesis promoting transcription factors and knock-down of induced hindering factors. The overexpression of neurogenesis promoting transcription factors and the knock-down of induced hinders are expected to become an effective method for improving the transdifferentiation efficiency and generating more new neurons, so that the method can be widely applied to the treatment of various nervous system diseases related to neuron loss, such as neurodegenerative diseases, central nervous system traumatic diseases and the like.

RE1 / NRSE blockers are used for treating nervous system diseases. This disclosure relates to the field of biomedicine. More specifically, this disclosure relates to the use of RE1 / NRSE elements as targets for transdifferentiating non-neuronal cells into neuronal cells; and the use of RE1 / NRSE blockers in preventing and / or treating diseases associated with neuronal loss or death. This disclosure provides methods for blocking RE1 / NRSE elements to regulate the expression of neuron-related genes in non-neuronal cells, which include reducing the binding of REST to RE1 / NRSE elements, or reducing the amount or activity of REST. This disclosure also provides RE1 / NRSE element blockers, especially the binding domains of endogenous RE1 / NRSE-binding proteins and their variants, which can be used for preventing and / or treating diseases associated with neuronal loss or death.

Combination therapies for the treatment of cancers are provided. In some aspects, a nucleic acid encoding a transdifferentiation determinant is administered in combination with a chemotherapeutic, electric fields therapy (e.g., TTField), or electromagnetic fields therapy to synergistically treat a cancer such as a glioma or glioblastoma (GBM).

Provided is a method for production by direct transdifferentiation of somatic cells into another somatic cells which is convenient, has good reproducibility, is excellent in production efficiency, and is performed in a short period of time. The method for production by direct transdifferentiation of somatic cells into another somatic cells comprises: (a) a step of introducing a GLIS family gene, a mutated GLIS family gene or a gene product thereof into somatic cells; and (b) a step of culturing the gene-introduced somatic cells in a culture medium containing a component that induces differentiation of the somatic cells or precursor cells of the somatic cells into another somatic cells.

The present application provides a method for in vitro purified corneal limbal stem cells to be transdifferentiated into lens spherules, specifically, the present application inoculates corneal limbal stem cells onto a culture plate containing a Matrigel glue layer, and cultures the corneal limbal stem cells in a culture system containing Y-27632 additives in LSCM culture solution, so that lens spherule organoids can be obtained. The method of the present application can realize the rapid transdifferentiation of corneal limbal stem cells into lens spherules, so that they can be implanted into the capsular bag as seed cells for in situ regeneration of the lens.

The invention relates to the field of biological medicine, in particular to a si-RNA composition for inducing cardiac fibroblasts to transdifferentiate into endothelial cells and application of the si-RNA composition. The si-RNA composition comprises a si-RNA (Ribonucleic Acid) aiming at a gene Huwe1, a si-RNA aiming at a gene Ltbp3, a si-RNA aiming at a gene Dysf and a si-RNA aiming at a gene Hivep3. The HLDH (Huwe1, Ltbp3, Dysf and Hive3) combined knockout can be used for successfully inducing the transformation of fibroblasts into endothelial cells in an in-vitro ischemia and hypoxia state. A carrier containing shRNA capable of expressing and generating the si-RNA composition is delivered into the heart, so that cardiac fibroblasts undergo transdifferentiation in vivo and participate in angiogenesis, and therefore, increase of fibrosis area and adverse ventricular remodeling after myocardial ischemia are limited through ways such as fibrosis remodeling, the heart function is retained, and myocardial ischemia is improved and repaired.

The invention discloses an application of a small molecular medicine composition in transdifferentiation of glioma cells. The small molecular medicine composition comprises LiCl, Pirfenidone, Forskolin and RO4929097, and the small molecular medicine composition comprises LiCl, Pirfenidone, Forskolin and RO4929097. The invention further discloses application of the small molecule medicine composition in treating glioma, preparing a medicine for treating glioma and preparing a medicine for inducing glioma cells to be transdifferentiated into neuron-like cells. According to the present invention, with the application of the small molecule drug combination, the glioblastoma line U251 can be induced into the neuron-like cells, the tumor proliferation and the subcutaneous tumor formation ability can be inhibited, and the median lifetime of the xenotransplantation brain glioma model mouse can be prolonged.

Compositions and methods are described herein for transdifferentiation of multipotent stromal cells into cells that can express insulin.

Enhanced methods for the generation of medial ganglionic eminence (MGE) cells from pluripotent stem cells are provided that involve an additional step of contacting the cells with an activator of FGF8 signaling while differentiating Pax6+ cells progenitor cells into MGE cells with an activator of sonic hedgehog, and optionally a Wnt inhibitor. The activator of FGF8 signaling shifts the differentiation of the population of cells to NKX2.1+ MGE cells, rather than to CopuTFII+ caudal ganglionic eminence (CGE) cells. Methods for treatment of neurological disorders, such as epilepsy, by transplant of MGE cells, or GABAergic interneurons derived from human pluripotent stem cells, into a subject in need of treatment are also provided. Human pluripotent stem cell derived MGE cells when transplanted successfully suppress spontaneous seizures, e.g. in epilepsy. We also have developed a method to purify MGE cells and maturing interneurons from differentiated pluripotent stem cells using cell surface marker and molecular beacon technology.

The application belongs to the technical field of biotechnology, and specifically discloses application of Olig2 in transdifferentiation of astrocytes into functional neurons, and provides overexpression of a neurogenesis-promoting transcription factor and knockdown of an inducible hindering factor, which are expected to be effective methods for improving transdifferentiation efficiency and generating more newborn neurons, and thus are widely applied to treatment of various nervous system diseases related to neuron loss, such as neurodegenerative diseases and traumatic diseases of the central nervous system.

This invention discloses a combination of biomarkers, a kit, and their applications for detecting hypertrophic scars (HTS). The biomarker combination includes a core biomarker and / or auxiliary biomarker 1 and / or auxiliary biomarker 2; the core biomarker is ABCC9 and CSPG4, auxiliary biomarker 1 is RGS5 and ACTA2, and auxiliary biomarker 2 is PDGFRB and TRPC6. This invention also provides a kit containing the above biomarker combination detection reagents and a drug screening method. This invention reveals for the first time that pathological pericytes are the core fibrotic cells in HTS, breaking through the traditional understanding that fibroblasts are the dominant cells. By targeting and inhibiting the abnormal activation, proliferation, and transdifferentiation of pericytes into myofibroblasts, the generation of myofibroblasts and matrix deposition are curbed at the source, providing a new strategy for precision treatment of HTS. Compared with traditional therapies, this approach has higher specificity and can achieve early molecular warning and quantitative detection of trace tissues for HTS, effectively overcoming the lag and subjectivity of clinical morphological diagnosis.

Provided are compositions of a system and methods of use thereof to transdifferentiate non-hair follicle stem (HFS) cells into non-auditory induced hair follicle stem cells (iHFSCs) and to subsequent use of these cells in the treatment of hair loss.

The transdifferentiation of glial cells into neurons is useful for prevention or treatment of a disease associated with loss of function or death. The present disclosure relates to the field of biomedicines. More specifically, the present disclosure relates to use of a REST inhibitor in the treatment of a disease associated with loss of function or death of neurons. The present disclosure can effectively induce transdifferentiation of astrocytes into dopamine neurons by inhibiting the expression, content or activity of a gene of REST or an RNA thereof or an encoding protein thereof in astrocytes in the brain, and can effectively induce transdifferentiation of Müller glia (MG) into retinal ganglion cells (RGCs) or photoreceptor cells by inhibiting the expression, content or activity of the gene of REST or the RNA thereof or the encoding protein thereof in the retina, thereby preventing and / or treating the disease associated with loss of function or death of neurons.

The invention discloses an induction culture medium for inducing fibroblasts to transdifferentiate into nucleus pulposus cells and application of the induction culture medium, and belongs to the technical field of cytobiology and regenerative medicine. The induction culture medium comprises a basic culture medium and an induction composition, can be used for realizing 2D / 3D transdifferentiation of fibroblasts into nucleus pulposus cells, and meets the requirements of different application scenes. Meanwhile, the invention further provides an amplification culture medium, a technical system for forming a 3D (three-dimensional) organoid through amplification of the amplification culture medium is provided, and the method has important significance in promoting cell therapy of the intervertebral disc degenerative change.

The invention relates to in vivo methods and compositions for converting one cell type to another cell type. In particular, the invention relates to transdifferentiation of a cell to a photoreceptor cell, preferably a rod photoreceptor cell. In one aspect, the invention provides an in vivo method for reprogramming a source cell, the method comprising increasing the protein expression of one or more transcription factors, or biologically active fragments or variants thereof, in the source cell, wherein the source cell is reprogrammed to exhibit at least one characteristic of a target cell, wherein the source cell is a glial cell, the target cell is a photoreceptor cell; and the transcription factors are one or more of those selected from ASCLI, NEURODI, NRL, NR2E3, RAX, RORB, OTX2, CRX and PAX6.

This disclosure relates to methods of inducing insulin production from pancreatic duct cells in response to glucose or transdifferentiating pancreatic duct cells into insulin-producing beta-like cells by administering an agent that inhibits aldehyde dehydrogenase family 3 member B2 (ALDH3B2) protein or an agent that inhibits the expression of ALDH3B2 gene. This disclosure also relates to methods of treatment of diabetes by administering an agent that inhibits ALDH3B2 protein or an agent that inhibits the expression of ALDH3B2 gene.

Disclosed herein are matrix-free and in vivo-like glioblastoma organoids (GBOs) developed using patient-derived xenograft GBM lines in small-scale bioreactors and a method of scalable biomanufacture thereof. Shear stress, agitation rate, and media supplements can be optimized to produce highly reproducible GBOs over 1 mm diameter within 4-5 weeks. GBOs can exhibit high stemness and strong cell-to-cell interactions compared to conventional tumorsphere cultures. They can display spatial gradients of HIF-1α positive hypoxic cores where CD133-positive cells resided and spatially heterogeneous expression of NOTCH and its ligands. A self-established, hierarchically organized, and heterogeneous TME by GBM transdifferentiation into endothelial cells, pericytes, and astrocytes can also be observed. Collectively, the ability to biomanufacture uniformly sized GBOs that recapitulate in vivo GBM TME features that can serve as an improved GBM in vitro model is demonstrated herein.

The present application relates to the field of cell reprogramming, and in particular to a method for inducing fibroblast transdifferentiation into kidney epithelial cells by using a double-stranded retrovirus vector combined with a double selection antibiotic screening strategy. The present application first applies a double-stranded retrovirus vector, and adds a Puromycin and Blasticin double-antibiotic screening strategy, to induce four transcription factors Hnf1beta, Emx2, Pax8 and Hnf4alpha to reprogram embryonic fibroblasts into kidney tubular epithelial cells within two weeks. The establishment of the technical system of the present application will provide strong technical support for obtaining kidney tubular epithelial cells in vitro.

The invention relates to a culture medium and method for transdifferentiating fibroblasts into heart valve endothelial-like cells and application of the culture medium and relates to the field of cell differentiation, and the culture medium comprises an induction culture medium I, an induction culture medium II, an induction culture medium III and an induction culture medium IV; according to the method, the human skin fibroblasts can be directly transdifferentiated into the heart valve endothelial-like cells in the induction culture media I-IV, a stem cell stage is not needed, a virus vector is not used for introducing transcription factors in the transdifferentiation process, and only small molecule compounds and cell factors are used; therefore, the technology has very high safety and a very wide application prospect.

The invention provides a small molecule compound combination. The small molecule compound combination is prepared from DAPT, LDN193189, CHIR99021, Ibet-762 and Isx9. The invention also provides application of the small molecule compound composition in treatment of glioma, preparation of drugs for treatment of glioma and preparation of drugs for inducing transdifferentiation of glioma cells into neuron-like cells. The invention also provides a method for inducing transdifferentiation of glioma cells into neuron-like cells. The method comprises the step of applying the small molecule compound combination. The small molecule compound composition can induce transdifferentiation of human glioma cells into neuronal cells, and has an inhibition effect on proliferation, migration, invasion and tumor formation capabilities of tumor cells.

The invention belongs to the field of biotechnology medicine, and particularly relates to a method for improving the induction efficiency of transdifferentiation from astrocytes to neurons, which comprises the following steps: preparing primary astrocytes: separating cortical tissues to prepare a cell suspension, and culturing and purifying to obtain the astrocytes. And transdifferentiation induction: transducing the astrocytes by using lentivirus, changing a differential medium and adding BDNF for culture to promote the astrocytes to be transdifferentiated into mature neurons. Animal model and targeted induction: establishing a cerebral infarction model, and injecting AAV-Neurog2-Pax6 virus into a focus area to realize specific transdifferentiation of astrocytes; the method comprises the following steps: performing in-vivo induction and sample treatment: performing perfusion fixation, dehydration, embedding and freezing slicing after taking materials, retaining the integrity of transdifferentiated cells, and performing overexpression on Neurog2 and Pax6 to realize transdifferentiation of the astrocytes to neurons and improve the induction efficiency of transdifferentiation of the astrocytes to the neurons.