221 results about "Mesenchyma" patented technology

The present disclosure relates to mesenchymal lineage precursor or stem cell mediated methods for treating severe Graft versus Host Disease (GvHD) in subjects at high risk of poor outcomes.

The invention is directed to methods of improving the therapeutic efficacy of mesenchymal stromal cells (MSCs) for use in treating osteoarthritis (OA), and more specifically to methods of altering levels of certain proteins, phospho-proteins, genes, and / or MSC-secreted cytokines, chemokines, and / or growth factors in order to improve therapeutic efficacy, as well as methods of distinguishing and classifying MSCs as being highly therapeutic or less therapeutic based on levels of certain phospho-proteins and / or MSC-secreted cytokines, chemokines, and / or growth factors and methods of treating a subject having OA with MSCs having improved therapeutic efficacy.

The present disclosure relates to cellular compositions that are modified to introduce a nucleic acid or vector expressing the same. Such compositions may be used to deliver nucleic acid to a target cell and treat disease such as cancer.

Provided herein are methods and related compositions for enhancing or enhanced partial reprogramming of target cells in a subject in need thereof (e.g., a human subject suffering from or at risk of a disease), the method comprising administering a plurality of mesenchymal lineage progenitor or stem cells (MLPSCs), exosomes derived therefrom, or conditioned culture media derived therefrom to a subject that expresses or will express one or more reprogramming factors in a population of target cells, whereby a plurality of the target cells in the subject become partially reprogrammed, but not fully reprogrammed.

The invention belongs to the technical field of application of plant exosomes, and discloses a plant-derived hybrid exosome and application of the plant-derived hybrid exosome in pulmonary fibrosis resistance. After screening a proper proportion, the obtained hybrid exosome has an obvious treatment effect on a mouse with pulmonary fibrosis induced by bleomycin, and the treatment effect is specifically shown as follows: (1) the hybrid exosome can obviously relieve lung inflammatory cell infiltration of the model mouse, protect a pulmonary alveolar structure and relieve the degree of pulmonary fibrosis; (2) the hybrid exosome can effectively reduce the expression levels of TNF-alpha, IL-1beta and IL-6, and can effectively slow down the pulmonary fibrosis process; the lung tissue inflammation is inhibited; and (3) the hybridized exosome inhibits the generation of ECM (extracellular matrix) and inhibits epithelial mesenchymal transition, so that the anti-fibrosis effect is achieved. The plant source hybrid exosome prepared by the invention is wide in plant source, simple in exosome preparation process and low in cost, and provides new possibility for treating pulmonary fibrosis.

The invention discloses a stem cell-derived function-enhanced mesenchymal stromal cell as well as a preparation method and application thereof. The preparation method comprises the following steps: inserting an IL-10 gene coding sequence and a CD47 gene coding sequence into a human pluripotent stem cell; a neural crest cell differentiation culture medium containing a Wnt pathway agonist and an ALK5 inhibitor is used for carrying out induced differentiation culture on the CD47 positive human pluripotent stem cells to obtain the neural crest cells. The neural crest cells are subjected to induced differentiation culture by adopting a transition culture medium containing an epidermal growth factor, a fibroblast growth factor 2 and a cell apoptosis inhibitor and a mesenchymal stromal cell differentiation culture medium containing the epidermal growth factor, the fibroblast growth factor 2 and a platelet growth factor in sequence; according to the present invention, with the combination of the specific embodiments, the obtained mesenchymal stromal cell highly expresses CD47 and IL-10, the expression of the CD47 can help the transplanted cell escape from the attack of the immune system and prolong the cell survival time, and the expression of the IL-10 can be used for anti-inflammation.

The present invention relates to CD73 + CD44 + , CD90 + A method for generating a population of mesenchymal stromal cells (MSCs) is provided. + CD44 + , CD90 + MSCs are used in methods to generate terminally differentiated osteogenic, adipogenic, and chondrogenic cells from pluripotent stem cells (PSCs), which involve the use of a single agent, a WNT signaling pathway activator (e.g., a GSK3β inhibitor), in adherent cultures of PSCs.

The generation of complex organ tissues from human embryonic and pluripotent stem cells (PSCs) remains a major challenge for translational studies. It is shown that PSCs can be directed to differentiate into intestinal tissue in vitro by modulating the combinatorial activities of several signaling pathways in a step-wise fashion, effectively recapitulating in vivo fetal intestinal development. The resulting intestinal “organoids” were three-dimensional structures consisting of a polarized, columnar epithelium surrounded by mesenchyme that included a smooth muscle-like layer. The epithelium was patterned into crypt-like SOX9-positive proliferative zones and villus-like structures with all of the major functional cell types of the intestine. The culture system is used to demonstrate that expression of NEUROG3, a pro-endocrine transcription factor mutated in enteric anendocrinosis is sufficient to promote differentiation towards the enteroendocrine cell lineage. In conclusion, PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development, homeostasis and disease.

The purpose of the present invention is to provide a novel medical application using pluripotent stem cells in regenerative medicine. The present invention provides a cell formulation and pharmaceutical composition that are for amelioration and therapy for frequent urination and bladder pain caused by the inflammation of the bladder and that contain SSEA-3 positive pluripotent stem cells isolated from cultured mesenchymal cells or a mesenchymal tissue of a living organism. The cell formulation according to the present invention is considered to be based on a mechanism in which, for example, Muse cells are administered against interstitial cystitis having the abovementioned disorders to be successfully engrafted into affected bladder tissue, whereby the disorders are ameliorated and treated.

The present disclosure relates to mesenchymal lineage precursor or stem cell mediated methods for treating severe Graft versus Host Disease (GvHD) in subjects that are refractory to at least two prior lines of therapy.

The invention relates to the technical field of biomedicine detection, and discloses a tumor cell marker detection system for predicting the activation state of intracellular protein kinase. Comprising a marker detection module used for qualitatively detecting epithelial cell markers, mesenchymal cell markers, cell polarity markers and extracellular matrix related markers in tumor cells; the data processing module is used for performing cross validation on an epithelial cell marker, a mesenchymal cell marker, a cell polarity marker and an extracellular matrix related marker; the dynamic weighting module is used for performing dynamic weighting on different markers based on a complex system theory, and endowing epithelial cadherin with a higher weight; and the judgment module is used for determining whether epithelial intercellular substance transformation occurs or not according to the dynamically weighted marker data, and predicting the activation state of intracellular phosphoinositide 3-kinase alpha and the invasiveness of tumor cells based on the determination result of the epithelial intercellular substance transformation.

The invention discloses a method for inducing fibroblasts to be reprogrammed into mesenchymal matrix-like cells (MLCs) by using small chemical molecules and application of the mesenchymal matrix-like cells (MLCs) in the anti-aging field. The invention discloses a set of specific chemical small molecule composition and an induction scheme thereof, which can be used for efficiently reprogramming fibroblasts from somatic cells into MLCs. Furthermore, the huge potential of the MLCs obtained by the method in anti-aging research is deeply explored, and the effect of the MLCs is proved to be obviously superior to that of umbilical cord mesenchymal stem cells in the aspects of reversing cell aging phenotypes and recovering tissue functions. The invention not only provides a new stem cell source strategy for avoiding the ethical and safety problems of the traditional reprogramming technology, but also lays a solid cell foundation for developing a novel, safe and effective anti-aging therapy based on cell transplantation or secreted factors.

The present application provides bispecific antibodies comprising a first antigen-binding fragment directed against human mesenchymal-epithelial transformation factor (c-Met) and a second antigen-binding fragment directed against human epidermal growth factor receptor (EGFR). In addition, the invention also provides medical and biological uses of the bispecific antibody.

A method of generating MSC-derived exosome populations may include collecting MSC containing material from living tissue, separating desired mononuclear cells from granulocytes, culturing to multiply the cells, separation of desired cells for further multiplication by washing non-adherent cells and culturing adherent cells, repeating as necessary to obtain a suitably pure population of MSCs, culturing the MSCs in culture media containing negative / healing active cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) and multifunctional cytokine TGF-ß, and isolating the MSC-derived exosome populations. Diverse MSC-derived exosome populations may be generated by altering the cytokine composition of the culture media. The MSC-derived exosome populations may be screened for effectiveness in treatment of Long Covid using in vitro, in vivo, and pre-clinical testing utilizing model organisms. The exosomes may be administered nasally. Successful MSC-derived exosome populations may be further subjected to patient trials to establish efficacy in treatment of Long Covid via nasal administration of the MSC-derived exosome populations to human subjects. Similar methodologies may be employed to establish efficacy of the MSC-derived exosome populations for treatment of other diseases and conditions related to the central nervous system, spinal cord injury, or neurological diseases, such as Alzheimer disease.

The invention relates to the technical field of cell preparation, and particularly discloses a cell drug and a preparation method thereof.The cell drug comprises mesenchymal cells and pharmaceutically acceptable auxiliary materials; the mesenchymal cell is characterized in that the expression of SOX2, DPPA4 and MYCN genes is negative; the auxiliary material comprises a sodium chloride solution containing albumin; the concentration of the sodium chloride solution is 0.1%-2%; the content of the albumin in the sodium chloride solution is 0.1%-10%. The cell medicine is simple in composition and good in auxiliary material compatibility, the motility of active ingredients can be protected, and the safety and reliability of the cell medicine are remarkably improved by optimizing the preparation process.

The invention provides a nucleic acid molecule, a mesenchymal stromal cell for promoting angiogenesis and application thereof, and relates to the technical field of biomedicine, the nucleic acid molecule encodes an HGF protein, or encodes a VEGF165 protein and an HGF protein; the first signal peptide is used as a signal peptide of VEGF165 protein, and the second signal peptide is used as a signal peptide of HGF protein. Through a gene modification strategy, the MSC cell containing the nucleic acid molecule stably and efficiently expresses VEGF165 and / or HGF, and the expression quantity of the VEGF165 and / or HGF is obviously higher than that of the MSC without the nucleic acid molecule. The capability of promoting endothelial cell migration is realized; meanwhile, the cells can also remarkably promote proliferation and tube formation of HUVEC cells, and the strong angiogenesis promoting effect of the cells is further proved. The technical problem that in the prior art, nucleic acid molecules for expressing VEGF165 or / HGF cannot be stably and efficiently expressed is solved.

The present invention provides chimeric antigen receptors (CARs) comprising an extracellular domain which specifically binds to Mesenchymal Epithelial Transition factor (MET); a transmembrane (TM) domain; a co-stimulatory signaling domain; and, a primary intracellular signaling domain. The application further relates to polynucleotides and recombinant vectors encoding the CARs, as well as to host cells and methods for producing host cells that express the CARs. The application further relates to pharmaceutical compositions comprising the CAR modified cells. Methods for stimulating elimination of a MET-expressing cell and for treating a MET-positive cancer using the CAR modified cells in a subject are also disclosed.

This invention relates to a method for expanding immune cells, the method comprising co-culturing the immune cells and at least one epithelial organoid, wherein the epithelial organoid comprises more epithelial cells than mesenchymal cells. Also provided are immune cells obtainable by the method, an in vitro population of innate lymphoid cells (ILCs) comprising at least 5×103 ILCs, pharmaceutical compositions and uses thereof.

This cell-based formulation contains SSEA-3-positive pluripotent stem cells derived from mesenchymal tissue of a living body or derived from cultured mesenchymal cells. This cell-based formulation is characterized in that the formulation is for administration to address diseases and / or post-acute sequelae caused by SARS-CoV-2 infection. The present invention makes it possible to provide a cell-based formulation that contains pluripotent stem cells and is used for treating and / or preventing SARS-CoV-2 infection-caused diseases such as pneumonia and pulmonary fibrosis and SARS-CoV-2 infection-caused post-acute sequelae such as olfactory dysfunctions.

The invention relates to the field of disease diagnosis, and particularly discloses a marker for olfactory neuroblastoma subtype classification, and the marker comprises a substrate type marker, a nerve type marker and a mesenchymal type marker. The typing gene expression profile used in the invention is derived from high-precision single cell sequencing, has high accuracy and distinction degree, and can be projected to ordinary transcriptome sequencing with relatively simple sequencing steps and low cost to obtain a typing conclusion, so that verification and popularization within a certain range are facilitated, and the method has a wide application prospect. The kit is helpful for typing ONB patients in clinical work, and assists corresponding drug treatment selection according to molecular characteristics of each subtype.

The invention relates to the application of inhibition of transcription factor 4 (TCF4 / ITF2) in the treatment of cancer. This in particular in combination therapy in conjunction with an immunotherapeutic compound (such as for treating cancers poorly responding or refractive to immunotherapy). In particular, inhibition of TCF4 / ITF2 is capable of restoring response to immunotherapy such as immune checkpoint inhibitor therapy. Expression levels of TCF4 / ITF2 as well as levels of mesenchymal-like cancer cells in a cancer lesion are predictive of future response to immunotherapy early after initiation of the immunotherapy. Further part of the invention are methods of detecting mesenchymal-like cancer cells.

The present invention relates to the discovery that different stem cell types (e.g., bone marrow-derived mesenchymal stem cells (RM-MSC) and adipose-derived mesenchymal stem cells (AT-MSC)) undergo large changes in lung epithelial marker 5 expression depending on the substrate on which they are cultured. The present invention includes methods and compositions for differentiating of mesenchymal stem cells, such as bone marrow and adipose tissue mesenchymal stem cells, into lung cells, populations of lung cells, and methods of alleviating or treating a lung defect in a subject in need thereof.

The invention discloses an application of glabridin in preparation of related drugs for inhibiting epithelial-mesenchymal transition in inflammatory bowel diseases. In the epithelial-mesenchymal transformation process, epithelial cells lose cell polarity and intercellular connection, are transformed into mesenchymal cells in function and morphology, directly participate in fibroblast activation and extracellular matrix deposition and cause intestinal fibrosis, and are one of anti-fibrosis targets. According to the application of the glabrione in preparation of the medicine related to inhibition of epithelial-mesenchymal transition in the inflammatory bowel disease, provided by the invention, the expression change of epithelial cell markers Claudin-1 and E-cadherin caused by TGF-beta 1 and interstitial cell markers Vimentin, N-cadherin, Snail and alpha-SMA can be relieved, cell migration caused by TGF-beta is improved, and the epithelial-mesenchymal transition induced by TGF-beta 1 is inhibited. The research on the mechanism of action shows that by blocking a TGF-beta1 / Smad2 / 3 signal channel and inhibiting AKT1 activation and inhibition of epithelial-mesenchymal transition, the application of the compound in inhibition of epithelial-mesenchymal transition and prevention of intestinal disease related fibrosis is prompted.

A method of increasing the chondrogenic potential mediated by TGFβ of a mesenchymal stromal cell (MSC) or a population of mesenchymal stromal cells (MSCs), comprising the step of increasing the amount of TGFβR1, and / or decreasing the amount of TGFβR2, and / or decreasing the amount of and / or ACVRL1 of the MSC or a population of mesenchymal stromal cells (MSCs).

Novel populations of canine derived stem cells useful for treatment across allogeneic barriers. The stem cells can be of mesenchymal lineage optimized to possess enhanced proliferative activity in vitro and in vivo without significant loss of therapeutic functionality. Said therapeutic activities include angiogenesis, stimulation of growth factor production, antifibrotic effects, neurogenesis, immune modulation, and antiapoptotic effects.

The purpose of the present invention is to provide a new medical use of pluripotent stem cells (Muse cells) in regenerative therapy. The present invention provides a cell preparation and a pharmaceutical composition for treating, preventing, alleviating and / or delaying onset of spinal cord infarction, comprising SSEA-3-positive pluripotent stem cells isolated from biologically derived mesenchymal tissues or cultured mesenchymal cells. The present invention is based on a mechanism in which Muse cells are administered to a subject having spinal cord infarction, and the cells are grafted to the tissue of the spinal cord infarction site, thereby treating spinal cord infarction.

An implantable membrane construct including a maximum pore size (MPS) less than 2 microns and opposing sides, each side of the construct having a surface roughness (Sa) greater than about 0.5 microns is disclosed. When the luminal surface of the implantable membrane construct has a surface roughness (Sa) greater than about 0.5 microns, mesenchymal cells do not form at the interface of the lumen and the first layer (i.e., luminal interface) such that the mesenchymal cells do not impede the flow of oxygen and nutrients to the graft cells (when implanted). When implanted, the outermost layer of the implantable membrane construct enables cellular penetration, vascularization, and anchoring of the construct. The implantable membrane construct includes single layer embodiments and multiple layer embodiments. Encapsulation devices utilizing the implantable membrane constructs to encapsulate biological entities (e.g., cells) into a patient are also provided.

The present invention belongs to the field of biotechnology and relates to the establishment of a SARS-CoV-2 envelope protein-induced renal fibrosis model. Specifically, it includes the establishment of a SARS-CoV-2 envelope protein-induced mouse renal fibrosis model and the establishment of a SARS-CoV-2 envelope protein-induced HK-2 cell epithelial-mesenchymal transition model. The present invention discloses for the first time a method for establishing a SARS-CoV-2 envelope protein-induced renal fibrosis model, which solves the problems of high cost and harsh operating conditions in the existing SARS-CoV-2 direct infection model establishment method, and provides a new experimental approach for further in-depth research on SARS-CoV-2-related renal pathological mechanisms and screening of related drugs.

An implantable membrane structure is disclosed that includes a maximum aperture (MPS) of less than 2 microns and opposing sides, each side of the structure having a surface roughness (Sa) of greater than about 0.5 microns. When the surface roughness (Sa) of the lumen surface of the implantable membrane structure is greater than about 0.5 microns, mesenchymal cells do not form at the interface of the lumen and the first side, i.e., the lumen interface, so that the mesenchymal cells do not hinder flow of oxygen and nutrients to transplanted cells (when implanted). When implanted, the outermost layer of the implantable membrane structure enables cell penetration, vascularization, and structural anchoring. The implantable membrane structure includes a single layer embodiment and a multi-layer embodiment. Encapsulation devices for encapsulating biological entities (e.g., cells) into a patient using implantable membrane structures are also provided.

The present invention generally relates to novel preparations of mesenchymal stromal cells (MSCs) derived from hemangioblasts, methods for obtaining such MSCs, and methods of treating a pathology using such MSCs. The methods of the present invention produce substantial numbers of MSCs having a potency-retaining youthful phenotype, which are useful in the treatment of pathologies.