2042results about "Non-embryonic pluripotent stem cells" patented technology

The invention relates to compositions (e.g., pharmaceutical compositions), uses, methods, non-therapeutic and therapeutic methods related to senolytic agents encapsulated or comprised in Muse cell derived extracellular vesicles (e.g. exosomes). Such compositions and methods are useful for specifically killing senescent cells and reverting any symptoms, disorders or diseases associated with senescence.

The invention belongs to the technical field of organoid culture, and particularly relates to a co-differentiated vascularized liver organoid and a construction method thereof. Aiming at the problems that the existing liver organ vascularization mostly adopts a co-culture mode, the operation process is complicated, the cell source heterogeneity is relatively high, the randomness is strong, the uniformity is poor and the like, the invention provides the construction method of the co-differentiated vascularized liver organ. The preparation method comprises the following steps: sequentially inducing and culturing directional endoderm cells, posterior preintestinal cells and hepatic endoderm cells, adding an S1 culture medium containing VEGF to induce and culture for 1-3 days, then adding an S2 culture medium containing VEGF, BMP4 and FGF2 to induce and culture for 3-5 days, and then adding an S3 culture medium containing VEGF to induce and culture for 14-20 days to obtain the co-differentiated vascularized liver organ. According to the method disclosed by the invention, the operation process is simplified, the experiment efficiency is improved, the liver organ which is rich in blood vessel network, high in maturity and of a blood vessel-bile duct structure is obtained, and a foundation is laid for large-scale production and clinical application.

The invention discloses for the first time pluripotent cells, including induced pluripotent stem cells, embryonic stem cells, hypo-immune pluripotent cells, cells that have been derived therefrom, and cells that have been biologically differentiated therefrom into particular tissue lineages that are ABO blood type O Rhesus Factor negative or otherwise evade rejection resulting from blood type antigen mismatch. The invention further provides universally acceptable “off-the-shelf” pluripotent cells and derivatives thereof for generating or regenerating specific tissues and organs.

The present application discloses an acetylated glucomannan electrospun membrane, and a preparation method therefor and a use thereof. The preparation method for an electrospun membrane of the present application comprises: first adding glucomannan into a mixed solution of pyridine and acid anhydride, carrying out solid-liquid separation after the reaction, collecting a solid phase, adding ethanol for precipitation, and collecting the precipitate to obtain acetylated glucomannan; then dissolving the acetylated glucomannan in a mixed solution of chloroform and N,N-dimethylformamide, and carrying out ultrasonic treatment to obtain an electrospinning solution; and finally, using the electrospinning solution as a raw material, and carrying out electrospinning to obtain an acetylated glucomannan electrospun membrane.

To provide senolytic agents to eliminate senescent cells and methods for treating diseases and disorders associated with senescence.SOLUTION: Disclosed is a method for removing senescent cells from banked stem cells, the method comprising adding to the stem cells at least one senolytic agent. Also provided is a pharmaceutical composition comprising at least one senolytic agent for use in a method for treating a disease, disorder or condition associated with senescence in a subject, where the method comprises removing stem cells from the subject, culturing the cells with the pharmaceutical composition, and administering to the subject the cultured cells.SELECTED DRAWING: None

The invention relates to a method of modulating the expression of an endogenous gene in a somatic cell derived from an induced pluripotent stem cell (iPSC), comprising differentiating an engineered iPSC capable of stable or inducible expression of a CRISPR-related protein into a somatic cell prior to introduction of a guide RNA (gRNA) sequence. The invention also relates to the engineered iPSC, cells obtained by the method and uses thereof.

Provided herein are compositions and methods for inducing an immune response in a subject, wherein the compositions comprise apoptotic cells, extracellular vesicles (EVs), and combinations thereof. Various compositions comprising mRNA encoding a microbial antigen are also provided. Further provided herein are compositions engineered to overexpress the human arrestin domain containing protein 1 [ARRDC1].

Embodiments of the invention include compositions and methods related to engineered human mucosal-associated invariant T (eMAIT) cells for off-the-shelf use for clinical therapy for cancer, infectious, and autoimmune diseases. In some embodiments, the eMAIT cells are produced from healthy human donor peripheral blood, cord blood, or G-CSF mobilized peripheral blood. In particular embodiments, the eMAIT cells are produced from a pluripotent stem cell line and therefore can be of unlimited supply. In some embodiments, the eMAIT cells are engineered to express chimeric antigen receptors (CARs), or / and immune regulatory molecules, or / and allorejection resistance molecules. Embodiments of the invention also include compositions of matter comprising polynucleotides encoding mucosal-associated invariant T cell receptor alpha chain polypeptides and / or mucosal-associated invariant T cell receptor beta chain polypeptides.

The invention relates to a cochlea spiral neuron in-vitro organ as well as a construction method and application thereof, and provides a method for obtaining a mature inner ear neuron by utilizing human pluripotent stem cell differentiation in vitro and further constructing an inner ear neuron in-vitro organ on the basis of the mature inner ear neuron. The internal ear neuron in-vitro organoid function stage obtained by the method and the application thereof are also provided.

Provided are: a method for producing an organoid, the method comprising a step for culturing somatic stem cells in a culture medium containing an agonist of the interferon-γ receptor; and a culture medium for producing an organoid, the culture medium containing an agonist of the interferon-γ receptor.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes a survival factor, wherein the genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor.

The invention relates to the field of cell biology, and particularly discloses a method for preparing mesoderm progenitor cells from human pluripotent stem cells and an induced differentiation culture medium of the mesoderm progenitor cells. The method comprises the following steps: inoculating human pluripotent stem cells in a single cell state into a culture dish covered with matrigel; and inducing the human pluripotent stem cells to be differentiated into the mesoderm progenitor cells within 1-3 days by using the mesoderm progenitor cell induced differentiation culture medium. Wherein the mesoderm progenitor cell induced differentiation culture medium is composed of a basic culture medium and an additive, and the additive contains a B-27 additive, non-essential amino acid, glutamine, ascorbic acid, polyvinyl alcohol, a GSK-3 inhibitor and a CDK8 inhibitor. According to the method, the human pluripotent stem cells are subjected to induced differentiation by using the mesoderm progenitor cell induced differentiation culture medium with specific composition, the method does not depend on cloning of the pluripotent stem cells, a large number of high-uniformity mesoderm progenitor cells can be obtained through induced differentiation within 1-3 days, the induction efficiency is high, and the stability is high.

The invention belongs to the technical field of organoid culture, and particularly relates to a co-differentiated vascularized islet organoid and a construction method thereof. Aiming at the problems that the existing pancreatic islet organ vascularization mostly adopts a co-culture mode, the operation process is long, the difficulty is high, the randomness is realized, the uniformity is poor and the like, the invention provides the construction method of the co-differentiated vascularized pancreatic islet organ. The method comprises the following steps of: sequentially inducing and culturing directional endoderm cells, original intestinal canal cells and posterior preintestinal cells, and adding a culture medium containing VEGF (vascular endothelial growth factor), BMP4 (bone morphogenetic protein 4) and FGF2 (fibroblast growth factor 2) for culturing in subsequent induced differentiation, so as to obtain the co-differentiated vascularized islet organ. Under the condition that exogenous endothelial cells are not added, the iPS cells are directionally differentiated to generate the vascularized islet organ containing beta, alpha and delta cells and vascular endothelial cells for the first time, the vascularized islet organ is more mature than non-vascularized islet organs and has a stronger insulin secretion function, and a new thought and an experimental basis are provided for realizing functional healing of diabetes mellitus.

The invention discloses a construction method of a homogenized self-assembled heart organoid, and belongs to the field of organoid. The preparation scheme of the heart organoid provided by the invention is controllable in method and simple in procedure, emphasizes the transition of differentiation from an iPSC 2D level to a 3D self-assembly heart organoid, overcomes the heterogeneity, including size, structure, function and even gene difference, of cross-batch or even same-batch organoid caused by an existing differentiation method, and has good cross-batch reproducibility. The constructed heart organoid contains various cell types and can continuously beat for at least 180 days in vitro, and the heart organoid in the same batch is uniform in height and stable in function. The preparation scheme does not need an engineering scaffold, matrigel and the like, emphasizes self-assembly of heart organs, and better accords with physiological characteristics of a human body.

The invention discloses a sheep formation state pluripotent stem cell culture medium and application thereof. The invention belongs to the technical field of biology, and particularly relates to a sheep formation state pluripotent stem cell culture medium and application thereof. The composition for culturing the sheep formation state pluripotent stem cells, disclosed by the invention, contains an N2B27 basic culture medium and cell factors, wherein the cell factors contain CHIR99021, IWR1, A419259, a recovery hub IL6, a recovery hub sIL6R, a recovery hub Activin A and a recovery hub FGF2 (Fibroblast Growth Factor 2). The culture medium prepared from the composition can obtain stable sfPSCs, and can be applied to construction of sheep gene editing model animals.

The invention belongs to the field of stem cell biology, and relates to pedigree specific differentiation of human pluripotent or embryonic stem cells, in particular to a mesenchymal stem cell induced differentiation culture medium and application thereof. The mesenchymal stem cell induced differentiation culture medium is used for directly inducing and differentiating human induced pluripotent stem cells / or embryonic stem cells into mesenchymal stem cells, the culture medium comprises a mesenchymal stem cell basic culture medium and an additive, and the additive comprises the following components: 2-10 [mu] M of a TGF-beta inhibitor, 2-10 [mu] M of a GSK3 beta inhibitor and 5-10 [mu] M of a Rock inhibitor. By adopting the induced differentiation culture medium provided by the invention, human induced pluripotent stem cells / or embryonic stem cells can be directly induced and differentiated into mesenchymal stem cells, and the obtained mesenchymal stem cells have the advantages of infinite sources, stable quality, high homogeneity and the like; and the human induced pluripotent stem cells / or embryonic stem cells can be directly and directionally differentiated into the mesenchymal stem cells in a relatively short time, so that the culture time is shortened, and the production cost is reduced.

The present invention relates to compounds for stabilizing cells, and methods of using the same, which prevent cell differentiation and promote cell survival, including but not limited to when the cells are isolated or when the cells exist outside of their normal culture medium or outside of a tissue environment. The present invention relates to two small molecule compounds, each of which acts by a slightly different mechanism but is useful as a preventative and therapeutic compound for a number of different disease indications, including, but not limited to, cancer, tissue injury, and stroke.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating the genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or component or transcriptional regulator of the MHC-I or MHC-II complex, at least one genetic modification that increases the expression of at least one polynucleotide that encodes a tolerogenic factor, and optionally at least one genetic modification that increases or decreases the expression of at least one gene that encodes a survival factor.

The problem addressed by the present invention is to provide a method for detecting undifferentiated pluripotent stem cells and a reagent for detection by measuring the amount of RNA expressed by MIR302CHG gene to enable detection of a small amount of remaining undifferentiated pluripotent stem cells.

The invention provides a preparation method of ovarian stem cells and application of the ovarian stem cells in ovarian aging resistance. More specifically, ovarian stem cells and polypeptide LRP-C5 which is separated from pilose antler polypeptide and has a good ovarian aging treatment effect are prepared and screened from ovaries, ovarian aging of rats can be well treated after the ovarian stem cells and the polypeptide LRP-C5 are used independently or jointly, and the application prospect is good.

The invention relates to the technical field of biological medicines, in particular to a preparation method of extracellular vesicles derived from myocardial cells derived from human induced pluripotent stem cells as well as a product and application of the extracellular vesicles. The method comprises the following steps: pretreating human induced pluripotent stem cell derived myocardial cells (hiPSCs-CMs) by using honokiol, and culturing the treated human induced pluripotent stem cell derived myocardial cells to collect extracellular vesicles (EVs) secreted by the human induced pluripotent stem cell derived myocardial cells. The extracellular vesicles secreted by the myocardial cells derived from the human induced pluripotent stem cells pretreated by honokiol are rich in functional mitochondria, show a better myocardial infarction treatment effect in animal experiments, and have huge clinical potential.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating the genetically modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or component or transcriptional regulator of the MHC-I or MHC-II complex, at least one genetic modification that increases the expression of at least one polynucleotide that encodes a tolerogenic factor, and optionally at least one genetic modification that increases or decreases the expression of at least one gene that encodes a survival factor.

An object of the present invention is to provide a cell population suitable for transplant of retinal tissue and a method of production thereof. The present invention provides a cell population for transplant, comprising retinal cells with a modified bipolar cell-regulating gene and a method of production thereof.

The present invention relates to a method of transiently inducing aging in stem cells or somatic cells derived from induced pluripotent stem cells (iPSCs) by forward programming, the method comprising introducing one or more aging-inducing factors into the cell or exposing the cell to one or more exogenous aging-inducing factors for a period of time, the one or more aging-inducing factors are then removed or reduced, such as before or after forward programming of the iPSC, resulting in a reversal of the one or more aging phenotypes in the cell. Also provided are artificially aged stem cells or somatic cells derived from iPSC by forward programming, and their use in methods of identifying genes or combinations of genes involved in aged phenotype reversal or non-aged phenotype maintenance in cells. Also provided are methods of identifying a gene or combination of genes involved in aging phenotype reversal or non-aging phenotype maintenance in a cell comprising introducing one or more aging-inducing factors into the cell or exposing the cell to one or more exogenous aging-inducing factors for a period of time, and measuring the aging phenotype of the cell. In particular, methods of identifying a gene or combination of genes involved in aging phenotype reversal or non-aging phenotype maintenance in a cell optionally include loss of function, inhibition, knockout, function acquisition, or combination screening. Also provided is a method of regenerating somatic cells comprising altering the expression and / or activity of one or more genes identified by the methods described herein.

The present invention relates to a method for preparing a mammalian vascular network or mature mammalian bone marrow organoid. Also provided is the use of the prepared vascular network or mammalian bone marrow organoid in the treatment of bone marrow-related diseases, in vitro generation of BMO or mammalian blood cells, as a model system for the pathogenesis of bone marrow-related diseases, and as a system for identifying and / or testing pharmaceutically effective compounds for the treatment or prevention of bone marrow-related diseases.

Provided are a RIC cell, and a preparation method therefor and application thereof. The present invention particularly relates to the lineage-specific differentiation of a pluripotent or multipotent stem cell, specifically to a RIC cell differentiated from a stem cell, and a preparation method therefor and application thereof.

The present invention relates to a modified stem cell and an ex vivo method for preparing defined mature cells from genetic programming of said modified stem cell which can be carried out in absence of certain growth factors, as well as a kit allowing to transform stem cells, and the different uses of the mature cells, for example for in vitro drug screening and toxicology or as cultivated meat. The genetic programming involves a molecular switch between two mutually exclusive programs of stem cell expansion and differentiation. The invention may be used for stem cells or other progenitors cells of any type, from any eukaryotic organism, but finds particular application in pluripotent stem cells from humans and livestock animals.

The invention provides a human pluripotent stem cell single cell cloning method and a culture medium thereof, and belongs to stem cell culture. A single cell is inoculated into a 96-hole or 384-hole culture plate by utilizing a limited dilution technology, and meanwhile, the proliferation process of the single cell is tracked and recorded in real time by virtue of a living cell analysis system, so that the obtained clone is ensured to be derived from the single cell. According to the method provided by the invention, a large number of clone groups derived from single cells can be simply, conveniently, quickly and easily obtained, and a solid foundation is laid for future large-scale production and industrial technical platforms.

The present invention discloses a method for enhancing cardiomyocyte production from induced pluripotent stem cells (iPSCs) by adjusting the culture medium exchange process during the transition from WNT activation to inhibition for differentiation. Instead of completely replacing the culture medium, this innovative technique involves partially changing the medium, which allows for a controlled exposure to WNT activators concurrent with the introduction of WNT inhibitors. This key modification in the protocol markedly increases the consistency and efficiency of cardiomyocyte generation, reducing variability between batches. By fine-tuning the medium exchange process, this method streamlines the creation of cardiomyocytes for use in regenerative medicine, emphasizing the critical adjustment phase within the culture conditions.