786 results about "Progenitor cell" patented technology

The purpose of the present invention is to provide a lipid composition capable of delivering a nucleic acid such as RNA to a hematopoietic stem / progenitor cell or a mesenchymal stem cell, and a method for delivering a therapeutic agent to a cell using the lipid composition. The present invention provides a lipid composition comprising (A) a therapeutic agent and (B) a lipid nanoparticle conjugated to a targeting molecule wherein the lipid nanoparticle comprises an ionizable lipid and the targeting molecule specifically binds to a marker of hematopoietic stem / progenitor cells or mesenchymal stem cells.

Disclosed herein are methods and systems of determining a cancer status or an organ health status of a subject, the method comprising: obtaining a biological sample obtained or derived from the subject; enriching a population of cells in the biological sample, wherein the population of cells comprises stem cells and / or progenitor cells; extracting nucleic acids from the enriched population of cells; assaying the extracted nucleic acids to generate at least one of a transcriptomic profile of the subject, a genomic profile of the subject, and / or an exomic profile of the subject; computer processing the at least one of the transcriptomic profile of the subject, the genomic profile of the subject, and / or the exomic profile of the subject; and determining, based at least in part on the computer processing, the cancer status or the organ health status of the subject, wherein the cancer status or the organ health status comprises a presence or an absence of an organ and / or a tissue impacted by the cancer or impacted by a disease, disorder, or condition.

The invention discloses an antibody-modified lipid nanoparticle, a preparation method thereof and application of the antibody-modified lipid nanoparticle as a targeting carrier. The invention provides lipid nanoparticles coupled with an antibody and loaded with nucleic acid. The lipid nanoparticles are characterized in that raw materials of the lipid nanoparticles consist of ionizable lipid, phospholipid, steroidal lipid, PEG lipid and PEG-Mal lipid, the PEG lipid is C16-PEG2k, and the PEG-Mal lipid is C16-PEG2k-Mal, and the PEG-Mal lipid is C16-PEG2k-Mal. The method aims at the key scientific problems of low delivery efficiency, insufficient targeting and the like in the field of in-vivo hematopoietic stem / progenitor cell gene therapy at present. The invention develops a lipid nanoparticle delivery system based on antibody modification, provides a modular antibody targeted delivery platform with high universality, and shows huge clinical transformation potential.

The invention relates to a cell differentiation trajectory inference method based on deep hyperbolic manifold embedding. The method comprises the following steps: acquiring single-cell RNA sequencing data; introducing hyperbolic space embedding with negative curvature, performing feature extraction on the single-cell RNA sequencing data through a deep feature extraction network, and mapping extracted high-dimensional features to a low-dimensional hyperbolic space; through track inference in a low-dimensional hyperbolic space, transformation paths of cells from progenitor cells to various differentiation end cell types are constructed, and key genes and pathways are evaluated by utilizing a sensitivity analysis method. The method has the beneficial effects that by introducing hyperbolic space embedding with negative curvature, the model can better capture the hierarchical structure of data, and the accuracy and consistency of differentiation tracks are enhanced. Moreover, high-dimensional single-cell sequencing data can be processed, the limitation of a traditional method under the high-dimensional condition is overcome, and the applicability of the model is improved.

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 relates to the field of biological medicine, and provides an application of a dihydroorotate dehydrogenase inhibitor in preparation of megakaryocytes, and the dihydroorotate dehydrogenase inhibitor is a compound shown as a formula I, a formula II or a formula III, or a pharmaceutically acceptable salt of the compound. According to the technical scheme, the dihydroorotate dehydrogenase inhibitor can promote hematopoietic stem / progenitor cells to differentiate into megakaryocytes and platelets, the platelet generation amount is increased by about 2 times, and a promising strategy is provided for in-vivo and in-vitro megakaryocyte and platelet generation.

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 present disclosure describes gene editing systems and therapeutics for use in treating VEXAS syndrome. In particular, the disclosure describes lipid nanoparticles that enhance the targeted delivery of gene editing systems and therapeutics to blood cell progenitor cells, enabling treatment of VEXAS syndrome, in vivo or ex vivo.

The invention discloses an antibody combination and a system for detecting leukemia stem cells. The antibody combination comprises a CD7 antibody, a CD371 antibody, a CD34 antibody, a CD45RA antibody, a CD123 antibody, a CD133 antibody, a CD38 antibody, a CD45 antibody, a CD90 antibody, a CD33 antibody and a CD19 antibody. The antibody combination provided by the invention can accurately identify target cells and distinguish normal HSCs and pluripotent progenitor cells in a CD34 + CD38-cell population, and the specific antibody has abnormal expression or expression intensity change, so that leukemia stem cells can be rapidly, simply and conveniently detected with high accuracy, high sensitivity and high specificity, the sensitivity of MRD evaluation is favorably improved, and the kit has a good application prospect. Therefore, signs of disease recurrence can be found earlier, more information about disease prognosis can be provided, and doctors and patients can be helped to better understand disease prognosis and possible results.

The invention discloses a circRNA nano delivery system capable of reversing nucleus pulposus progenitor cell senescence and a preparation method and application of the circRNA nano delivery system. The circRNA nano delivery system comprises: a) Klotho circRNA, and b) a liposome, and the liposome comprises a vascular peptide vasculotide, an ionizable lipid molecule, a phospholipid, a PEG lipid, and a steroid. The invention also provides application of the circRNA nano delivery system capable of reversing nucleus pulposus progenitor cell senescence in preparation of drugs for treating intervertebral disc degeneration. The invention provides liposome particles (Vas-Klotho-LNP) which have targeted NPPCs and wrap circRNA, Klotho circRNA is efficiently introduced into the NPPCs through Tie2 agonist peptide, so that rejuvenation of the NPPCs is promoted, ECM synthesis is promoted, and regeneration and repair of intervertebral discs are synergistically promoted in vivo and in vitro.

Disclosed herein are methods of treating ALS in a subject by administering a therapeutically effective amount of a composition comprising EVs, e.g., derived from neural cells, e.g., neural progenitor cells, to the subject. The EVs can be administered distally or peripherally to the CNS, such that the EVs cross the blood brain barrier and exert their therapeutic function in the CNS. The methods can reduce inflammation (e.g., NLRP3 inflammatory pathway signaling), reduce disease activity or progression, and / or improve motor or neurological performance, signs or symptoms associated with ALS, or survival in the ALS subject as compared to a control ALS subject. The methods of inhibiting necroptosis in a cell by contacting the cell with a therapeutically effective amount of a composition comprising EVs are also provided.

The present disclosure provides a method for delivery of cargo to a haematopoietic stem or progenitor cell of a subject, the method comprising contacting a lipid nanoparticle encapsulating the cargo with the haematopoietic stem or progenitor cell ex vivo or in vivo, thereby causing cellular uptake of the cargo, the lipid nanoparticle having between 30 mol% and 70 mol% of a neutral or zwitterionic amphipathic lipid having a net-neutral charge at physiological pH, an ionizable cationic lipid, and a sterol, wherein the lipid nanoparticle is substantially uncharged at physiological pH and has an apparent pKa of between 6.0 and 7.5. Further provided are lipid nanoparticle compositions and uses thereof.

The invention relates to a method for efficiently inducing human hematopoietic stem progenitor cell erythroid to be directionally differentiated into mature erythrocytes in a serum-free and feeder-layer-free manner, which adopts a serum-free and feeder-layer-cell-free induction culture system, and uses an mTOR pathway inhibitor rapamycin to regulate the activity of an mTOR pathway in the erythroid differentiation process. The use dosage and the treatment mode of the mTOR pathway inhibitor rapamycin are further optimized, and the erythrocyte denucleation efficiency of an in-vitro induced differentiation system is remarkably improved to 70% under the condition that erythrocyte proliferation and differentiation are not affected or the cell state is not reduced. According to the method, heterologous pollution caused by animal serum or heterologous cells is effectively avoided, the clinical safety of in-vitro preparation of transfusion-level red blood cells in the future is ensured, the erythroid directional induced differentiation final maturation efficiency of the human hematopoietic stem progenitor cells is improved, meanwhile, the reagent cost is reduced, and large-scale preparation and clinical transformation are facilitated.

The disclosure includes compositions and pharmaceutical compositions and kits comprising novel brain progenitor cells. In some embodiments, the disclosure relates to methods of making the cell lines as well as methods of using the cell lines to perform functional assays while being manipulated in culture.

Methods for differentiating pluripotent stem cells to neuroectoderm in dynamic suspension culture using small molecule or protein inhibitors of TGFβ / Activin / Nodal signaling and BMP signaling are provided. Also provided are methoc and protocols for differentiating pluripotent stem cells such as human embryonic stem cells first to neuroectoderm, then further to glial progenitor cells, and further to oligodendrocyte progenitor cells (OPCs), and compositions obtained thereby. The methods of the present disclosure reproducibly produce neuroectoderm progenitor cells by day 7 of the differentiation process, glial progenitor cells by day 21 of the differentiation process and OPCs by day 42 of the differentiation process.

The present invention discloses an application of highly active human umbilical cord mesenchymal stem cells. HA-MSCs were isolated from human umbilical cord tissue using TeSR-E8 containing 5% CloneR and LN521-Coated culture flasks, and a technical system for HA-MSC isolation, expansion, and cryopreservation was established. Compared with conventionally cultured MSCs, the HA-MSCs prepared by the present invention have higher proliferation activity, smaller size, a higher nuclear-cytoplasmic ratio, and highly express embryonic stem cell-associated marker antigens SOX2, Nanog, and OCT4. They have the potential to differentiate into neural, myocardial, and hepato-intestinal progenitor cells derived from the three germ layers and possess excellent anti-aging activity.

The invention provides an anti-tumor modification method of stem / progenitor cell-derived neutrophil, which comprises the following steps: extracting mouse bone marrow-derived Lin-progenitor cells and human umbilical cord hematopoietic stem / progenitor cells, modifying ER-Hoxb8 progenitor cells by gene editing, and inducing the ER-Hoxb8 progenitor cells into neutrophil; three modification strategies of chimeric antigen receptor CAR gene engineering modification, high expression MET gene modification and high expression of IFN-gamma while the TGFBR2 gene is stably knocked out are respectively adopted, and the anti-tumor phenotype of the neutrophil N1 is maintained. Compared with the prior art, the engineering neutrophile granulocyte has the following advantages that the engineering neutrophile granulocyte prepared by the method has the advantages of infinite sources, long-time preservation, safety, controllability, efficient and rapid preparation and the like; the engineered neutrophil can maintain the N1 antitumor phenotype and promote the antitumor function; the immunosuppression microenvironment of the solid tumor can be improved and the treatment effect can be improved by singly using or combining the immune checkpoint inhibitor.

The present disclosure provides methods of treating anemia in a patient in need thereof, comprising administering to the patient in need thereof an effective amount of salmeterol or a pharmaceutically acceptable salt thereof. Salmeterol or a pharmaceutically acceptable salt thereof may be administered conjointly with an erythropoiesis-stimulating agent, optionally wherein the anemia is refractory to the erythropoiesis-stimulating agent. Also provided are methods of promoting differentiation of an erythroid progenitor cell toward a mature red blood cell in a patient in need thereof, comprising administering an effective amount of salmeterol or a pharmaceutically acceptable salt thereof. The present disclosure further provides methods comprising administering salbutamol or a pharmaceutically acceptable salt thereof. Salmeterol, salbutamol, or a pharmaceutically acceptable salt thereof may be administered conjointly with other FDA-approved drugs such as luspatercept, lenalidomide, daprodustat, vadadustat, an erythropoiesis-stimulating agent (ESA), and / or a hypomethylating agent.

Provided is a method for preventing or treating optic neuropathy, comprising administering a pharmaceutical composition including neural progenitor cells as an active ingredient, where the neural progenitor cells not only exhibit remarkably superior neuroprotective and pro-regenerative effects compared to mesenchymal stem cells such as placenta-derived stem cells (e.g., PSCs), but also can be administered by non-invasive and safe subtenon injection, and therefore the method may be advantageously used as a cell therapy for treating optic neuropathy.

Methods for generating human vascular leptomeningeal cells (VLMCs) from human oligodendrocyte progenitor cells (OPCs) are provided using chemically-defined culture media that allow for generation of differentiated cells in a 34-day culture protocol. Methods of generating human VLMCs from human pluripotent stem cells using chemically-defined culture media in a 40 day culture protocol are also provided. Culture media, isolated cell populations, and kits are also provided.

Described herein are compositions and methods for modifying eukaryotic cells, for example, to express a transgene of interest and / or to produce an expanded population of cells ex vivo. Using the compositions and methods of the disclosure, a population of eukaryotic cells, such as a population of pluripotent cells (e.g., CD34+ hematopoietic stem or progenitor cells) may be transduced to express a gene of interest by contacting the cells with a viral vector, such as a lentiviral vector, and a diblock copolymer, such as a diblock copolymer composed of a hydrophilic region and a hydrophobic region. For example, the diblock copolymer may be composed of polyoxyethylene (PEO) subunits and polyoxypropylene (PRO) subunits. Additionally, the compositions and methods described herein can be used to promote the proliferation or survival of a population of pluripotent cells (e.g., CD34+ hematopoietic stem or progenitor cells) ex vivo, for example, by contacting the cells with a diblock copolymer.

The invention provides application of GDF15 in preparation of a medicine for treating or preventing hematopoietic dysfunction caused by DON poisoning. The research finds that the GDF15 has the effects of treating or preventing bone marrow total cell reduction, hematopoietic stem progenitor cell damage, erythroid progenitor cell damage, erythroid end developmental stage damage, reticulocyte number reduction and peripheral blood mature erythrocyte damage caused by DON poisoning, and the exogenous GDF15 can relieve inhibition of DON poisoning on cell growth and development through research. And a GDF15-beta-catenin-Myc signal channel is activated, so that the downstream Myc, p27 and p21 are normally expressed. The invention discloses a new application of GDF15 in treatment of DON poisoning.

The invention belongs to the field of biological medicine, and particularly relates to lipid nanoparticles, application thereof and a drug delivery carrier. The lipid nanoparticle comprises an ionizable lipid, cholesterol, phospholipid, a pegylated lipid and a sterol substitute, and is characterized in that the ionizable lipid is Lipid 5, the phospholipid is DSPC, the pegylated lipid is 18: 0 mPEG2000 PE, and the sterol substitute is one or more of beta-sitosterol, stigmasterol or stigmasterol or a derivative thereof; the molar ratio of the ionizable lipid to the cholesterol to the phospholipid to the pegylated lipid to the sterol substitute is (40-60): (5-38.5): (5-30): (1-2): (5-38.5). According to the invention, the LNP with unique physicochemical properties is constructed through high synergy of the components, the technical problems of low delivery efficiency and poor specificity of hematopoietic stem progenitor cells in the prior art are solved, and high-efficiency and high-specificity drug delivery of HSPCs in vivo and in vitro is realized. The invention also provides a drug delivery carrier containing the lipid nanoparticles and a preparation method thereof.

Methods for differentiating pluripotent stem cells to neuroectoderm in dynamic suspension culture using small molecule or protein inhibitors of TGFβ / Activin / Nodal signaling and BMP signaling are provided. Also provided are methot and protocols for differentiating pluripotent stem cells such as human embryonic stem cells first to neuroectoderm, then further to glial progenitor cells, and further to oligodendrocyte progenitor cells (OPCs), and compositions obtained thereby. The methods of the present disclosure reproducibly produce neuroectoderm progenitor cells by day 7 of the differentiation process, glial progenitor cells by day 21 of the differentiation process and OPCs by day 42 of the differentiation process.

The present invention relates to the new use of an exosome secreted by hepatocyte lineage cells differentiated via the directed induction of embryonic stem cells, and in particular relates to the use of the exosome in the preparation of a drug for treating liver diseases. The exosome is secreted by hepatocyte lineage cells differentiated via the directed induction of embryonic stem cells, and the hepatocyte lineage cells are hepatic progenitor cells and / or mature hepatocyte-like cells.

There is provided a hydrogel, such as a functionalized hydrogel, for use in the expansion and / or differentiation of cells, that are encapsulated within the three-dimensional structure of the hydrogel. In some aspects of the invention, the hydrogel better mimics the thymus microenvironment than prior hydrogels for T cell expansion and differentiation and can be used in the expansion and differentiation of HSPCs, HSCs or PCs or combinations thereof in the production of T cells, T-cell committed precursors or progenitor cells and in methods for producing mature T cells. Methods of making the hydrogels, methods of culturing the cells in the hydrogel and uses of the hydrogels and cells produced are also described.

The present invention provides methods of constructing vascularized retinal organoids by differentiating retinal progenitor cells and endothelial cells. The method is co-cultured by differentiating retinal progenitor cells and endothelial cells, and comprises the following steps: carrying out multiplication culture on pluripotent stem cells until the cell confluence degree is 80-90%, and digesting; carrying out differentiation culture on the digested pluripotent stem cells in a culture medium containing retina induction factors to obtain retina progenitor cells; and co-culturing the retinal progenitor cells differentiated for 12-13 days and endothelial cells to obtain the vascularized retinal organ, wherein the endothelial cells are obtained by any one method of induced differentiation of digested pluripotent stem cells or culture of endothelial cell lines. The vascularized retinal organ with the retinal layered structure is constructed by integrating the endothelial cells and the retinal progenitor cells for the first time, and the limitation that in the prior art, the retinal organ lacks vascularization is successfully overcome.

Provided are methods of obtaining large scale cultures of muscle-derived muscle precursor cells (MPCs) using microcarriers as growth matrices, methods for obtaining therapeutically effective amounts of these cells, populations of cells obtained by the methods, and compositions comprising expanded cells, and a method for preparing a medicament, for example for the treatment of skeletal muscle dysfunction.

The invention belongs to the technical field of organoid culture, and particularly relates to a pulmonary alveolar organoid with an endogenous vascular network and a construction method of the pulmonary alveolar organoid. Aiming at the problems that mesoderm and endoderm are difficult to induce at the same time, the operation process is long, the difficulty is high and the like when a vascularized alveolar organ is constructed by an existing method, the invention provides the construction method of the alveolar organ with the endogenous vascular network. The method comprises the following steps: simultaneously and directionally inducing and differentiating human induced pluripotent stem cells (hiPSC) into fixed endoderm and mesoderm, anterior intestine endoderm, abdominal side anterior intestine endoderm and lung progenitor cells by adopting a one-step method, and promoting endothelial cell proliferation in an endogenous induced differentiation process through a specific growth factor combination. A functional vascular network is formed; and vascularized alveolar organs are induced to be generated. According to the invention, a qi-blood barrier structure in which vascular endothelial cells and pulmonary epithelial cells are tightly connected is successfully reproduced, the gas exchange function of lung tissues can be simulated, and a new way is provided for construction of vascularized alveolar organs.

Provided herein are methods of generating Gata6-positive brown adipose progenitor cells, and brown adipose cells and tissue therefrom. Additionally, provided herein are methods of generating UCP1 positive organoids. Generally, the methods include a step of culturing brown adipose progenitor cells in a medium containing an FGF signaling pathway activator, a BMP signaling pathway activator, a TGFβ activator, a Wnt inhibitor, and a thyroid hormone receptor activator.