231 results about "Stromal cell" patented technology

The invention belongs to the technical field of functional nanoprobes and biological detection, and particularly relates to a kit for simultaneously detecting a specific membrane protein marker and a membrane protein dimer and application of the kit. The detection kit comprises a membrane proteome anchoring chain, a recognition probe, an SERS probe and an auxiliary signal amplification reagent, by combining DNA logic sensing based on aptamer recognition and logic response type assembly based on EpCAM protein expression and DNA signal amplification of Met protein dimerization, networked assembly of a recognition probe and an SERS probe is realized, so that specific accurate recognition of tumor cells and high-sensitivity SERS detection and imaging of membrane protein dimers are realized; the method is suitable for monitoring an HGF / Met signal channel based on Met protein dimerization mediation between stromal cells and cancer cells in a complex tumor microenvironment, and can evaluate the inhibition effect of a targeted drug on receptor dimerization in real time.

The invention provides a screening platform for chemotherapy combined anti-tumor natural products and application of the screening platform. PTC has tumor cells, interstitial cells, fibroblasts and immune cells from primary epithelium, is rich in cell components, and has advantages in the aspect of tumor microenvironment simulation. Meanwhile, PTC can reproduce tumor heterogeneity, the culture success rate and clinical consistency can reach 90% or above, and the detection period is within two weeks. And the detection result can be read through AI intelligent software, so that the accuracy can be further improved. The screening period can be shortened, the cost is reduced, and the accuracy is improved; according to the platform, high-throughput screening can be carried out in a short time, and the treatment effect of a chemotherapy drug combined anti-tumor natural product drug scheme can be predicted.

Aspects of the present disclosure provide engineered induced pluripotent stem cell (iPSC)-derived mesenchymal stromal cells (EiMSCs) that exhibit persistent transgene expression. Persistent transgene expression may be achieved through use of an engineered chromatin opening sequence (ECOS). The engineered EiMSCs of the present disclosure can comprise a therapeutic polypeptide comprising one or more cytokines for the treatment of a metabolic disease, a proliferative disease, an autoimmune disease, a neurological disease, or any combination thereof.

Disclosed is a method for producing T cells, the method comprising: (1) culturing three-dimensional cell aggregate(s) comprising cells that can differentiate into T cells, and stromal cells that express Notch ligand(s) derived from pluripotent stem cells. Also disclosed are T cells obtained by the method, and a medicine comprising the T cells.

The invention relates to the technical field of biology, and particularly provides an endometrial organ culture method. By optimizing the endometrial organoid differentiation culture system, compared with an existing culture mode, the optimized culture system is easy to operate, the organoid with more complete physiological functions can be prepared without co-culture with stromal cells, continuous culture can be conducted for at least one year or above, and the obtained organoid is complete in secretion function and free of secondary pollution. The phenotype of cilia cells is more obvious.

The present invention relates to a method for preparing organ-specific mesenchymal cells from pluripotent stem cell-derived intestinal organoid stromal cells. By using cells derived from stromal cell layers adjacent to intestinal organoids for differentiation into organ-specific mesenchymal cells, the present invention can greatly increase the efficiency of differentiation into stromal cells through the regulation of retinoic acid (RA) and hedgehog (HH) signaling pathways, and can increase the expression of organ-specific markers without exhibiting undifferentiated state cell characteristics, and thus mesenchymal cells having well-simulated biological characteristics can be prepared.

In one embodiment, cells 12 are suspended inside a hollow capsule 11 including a semipermeable membrane, and the hollow capsule 11 is incubated in a culture medium to allow the cells 12 to aggregate inside the hollow capsule 11. The cells 12 are a mixture of dissociated target cells 14 and auxiliary cells 15 for assisting the aggregation of the target cells 14. The target cells 14 more easily aggregate in the presence of the auxiliary cells 15 than in the absence of the auxiliary cells 15. In another embodiment, dissociated cells 12 are suspended inside a hollow capsule 11 including a semipermeable membrane, and the hollow capsule 11 is incubated in a culture medium to allow the cells to aggregate inside the hollow capsule 11. The cells 12 include at least stromal cells. Thus, an aggregate 21 of the cells 12 is produced.

The invention provides a space-time 3D printing method for tumor microenvironment organoid, which comprises the following steps: printing shell gel microbeads, and printing core gel microbeads in the shell gel microbeads to obtain core-shell gel microbeads; carrying out irreversible cross-linking curing on the core-shell gel microbeads to form a stable structure, so as to obtain the tumor microenvironment organ-like model. In the process of printing the inner core gel microbeads in the shell gel microbeads, time dimension and / or space dimension regulation and control printing is carried out, so that the effect of constructing different tumor microenvironment characteristics is achieved. The'core-shell 'gel microbead structure is printed through space-time modulation, organoids and stromal cells can be positioned in the inner core gel layer and the outer shell gel layer respectively, organoid models of different tumor microenvironment characteristics of a space layered structure are constructed, self-assembly of tumor cells can be guided, the effect of regulating the initial state of the tumor cells is achieved, and the tumor microenvironment characteristic of the tumor cells is improved. The tumor organoid can keep a stable three-dimensional structure in the subsequent culture process.

The invention discloses a fructus lycii pigment composition for treating benign prostatic hyperplasia and application. The fructus lycii pigment composition comprises lycium barbarum red, zeaxanthine, xanthophyll and beta-carotene. The fructus lycii pigment composition provided by the invention can effectively inhibit prostate stromal cell proliferation, inhibit prostate tissue hyperplasia in vivo, improve the pathological morphology of prostate tissue, regulate the androgen level, inhibit inflammatory response and relieve oxidative damage. The traditional Chinese medicine is applied to clinical treatment of prostatic hyperplasia and has the advantages of remarkable curative effect and low toxic and side effects.

The invention discloses a bionic bone marrow microenvironment assembly for hematopoietic stem cell in-vitro amplification and a preparation method. The bone marrow microenvironment assembly comprises a three-dimensional scaffold and osteoblasts (OBs), wherein the three-dimensional scaffold comprises chitosan (CS) and sodium alginate (Alg) which are prepared into mixed gel, and the mixed gel is freeze-dried to prepare the three-dimensional scaffold; wherein the osteoblasts (OBs) are obtained by culturing and induced differentiation of umbilical cord mesenchymal stem cells (MSCs) inoculated on a three-dimensional scaffold, and the osteoblasts (OBs) as stromal cells and the three-dimensional scaffold jointly form the hematopoietic stem cell in-vitro amplification bionic bone marrow microenvironment assembly; in the hematopoietic stem cell in-vitro amplification bionic bone marrow microenvironment assembly, the preparation of the three-dimensional scaffold comprises the processes of freezing, remelting, freezing, crosslinking, freeze-drying and the like, so that a three-dimensional space form with wrinkles on the pore surface and pore size distribution between 70 microns and 400 microns is generated in the three-dimensional scaffold, and the three-dimensional space form is closer to a real stem cell niche; therefore, the practical application effect of the bionic bone marrow microenvironment assembly for in-vitro amplification of the hematopoietic stem cells is further improved.

The present invention provides a method of producing a population of mesenchymal stromal cells (MSC) of CD73 + CD44 +, CD90 +. The CD73 + CD44 +, CD90 + MSC is used in a method for producing terminally differentiated osteoblasts, adipoblasts and chondroblasts from pluripotent stem cells (PSCs). The differentiation methods include the use of a single agent-a WNT signaling pathway activator used on an adherent culture of PSC, such as a GSK3 [beta] inhibitor.

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.

It forms an object of the present invention a hollowed scaffold and a method to obtain the same, said hollowed scaffold being a milli-scale vessel-like structure comprising a microenvironment, a lumen, and a vessel wall, said microenvironment and said vessel wall being made, independently the one from the other, of a matrix, wherein in said matrix constituting said microenvironment stromal cells are embedded, and wherein in said matrix constituting said vessel walls endothelial cells are embedded. Additional objects of the present invention are a bioreactor comprising the hollowed scaffold and method to study cells in tissue-like vascularised constructs.

The invention discloses a preparation method of composite microspheres for regulating and controlling a local inflammation microenvironment and promoting nerve regeneration. The method comprises the following steps: preparing liposome loaded with ginsenoside Rg1; preparing a GM microsphere loaded with a stromal cell-derived factor 1 alpha (SDF1 alpha); and preparing the inflammation regulation nerve regeneration promoting composite microspheres. The composite microsphere can reduce inflammatory response, reduce scar tissue formation, promote angiogenesis, continuously release SDF1 alpha and promote endogenous stem cell recruitment and neural differentiation. Therefore, the composite microsphere is a functional biological scaffold for firstly regulating and controlling local microenvironment inflammation of spinal cord injury and then promoting collection and differentiation of endogenous stem cells for innovative sequential inflammation regulation and nerve regeneration, and a new strategy is provided for treating spinal cord injury by tissue engineering.

It was discovered that by binding to CTCF which is important for maintaining chromosomal structures, hSATII RNA inhibits the function thereof, changes chromosome interaction, and induces transcription of inflammation-associated genes. It has also been discovered that cell death can be selectively induced in senescent cells and cancer cells by suppressing hSATII RNA expression. From the obtained results, it has been found that cancer treatment which targets senescent stromal cells and cancer cells can be performed with a substance that suppresses hSATII RNA or a substance that increases CTCF expression. In addition, cancer can be detected early by measuring the expression and activity of hSATII RNA and CTCF, and an epigenomic change of the hSATII DNA region. Thus, it is possible to provide a therapeutic drug for a cancer associated with cellular senescence, a method for screening thereof, and a test support method.

Methods of differentiating a mesenchymal stromal cell (MSC) to a first non-MSC cell fate, the method comprising contacting the MSC with extracellular vesicles (EVs), matrix-bound vesicles (MBVs) or a combination thereof are provided. Methods of producing artificial tissue by culturing MSCs with two sets of vesicles each comprising EVs, MBVs or both that differentiate MSCs to two different non-MSC cell fates, methods of culturing with reduced growth factors and method of differentiating an MSC to a muscle cell fate are also provided.

Provided are antibodies that specifically bind to human urokinase-type plasminogen activator receptor (uPAR). In some cases, the antibodies are cross-reactive with one or more non-human animal uPAR polypeptides, such as non-human primate uPAR, e.g., cynomolgus monkey uPAR. Fusion proteins and conjugates comprising the antibodies of the present disclosure are also provided. Methods of using the antibodies, fusion proteins, and conjugates of the present disclosure to treat conditions associated with uPAR expression and / or activity are also provided. In some embodiments, the condition associated with uPAR expression and / or activity is cancer. Non-limiting examples of such cancers include cancers characterized by cancer cells expressing uPAR on their surface, cancers characterized by stromal cells within the tumor microenvironment expressing uPAR on their surface, and the like.

The current invention relates to a composition comprising extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs). The EVs are part of a population of particles in the composition having a particle size of between 0.05 and 0.22 micron. The concentration of these particles is at least 1×1011 particles per ml of composition. At least 90% of the particles with particle size of between 0.05 and 0.22 micron are EVs. The EVs are defined by having a concentration of intra-vesicular Annexin V of at least 40 ng / ml and a concentration of extra-vesicular Annexin V of less than 1 ng / ml. Uses of the composition also are disclosed.

The utility model relates to a kind of human adenomyosis ectopic epithelium and stromal cell separation culture devices. The device includes L-shaped base, fixed tube, centrifugal tube, filter separation component. Two centrifugal tubes are used to collect stromal cell and epithelial cell respectively, and the top end of centrifugal tube is connected with top cover. Filter separation component includes mounting ring, locating ring, flexible filter screen, annular frame and positioning mechanism. Mounting ring is horizontally arranged, locating ring is peripherally arranged on mounting ring, and locating ring is adapted to the top end of centrifugal tube, filter screen is arranged at the bottom of mounting ring, the bottom of annular frame is connected with the bottom surface of flexible filter screen, gap is provided between the top of annular frame and mounting ring, and annular frame is limited by positioning mechanism. Compared with prior art, the utility model can simplify the separation process of human adenomyosis ectopic epithelium and stromal cell, reduce cleaning work, and is suitable for laboratory culture operation.

This invention belongs to the field of biomedical technology, specifically relating to a rapid purification method for umbilical cord MSC exosomes and their application in the preparation of drugs for treating COPD. This invention discloses a method for rapidly purifying umbilical cord mesenchymal stromal cell (MSC) exosomes and a pharmaceutical composition comprising umbilical cord MSC exosomes and yamosaponin. In this pharmaceutical composition, the umbilical cord MSC exosomes and yamosaponin synergistically enhance the dynamic compliance of COPD rats, reduce airway resistance, decrease pulmonary inflammation, and repair pulmonary dysfunction. This invention provides a new technical solution for the preparation of drugs for treating or improving COPD.

The invention discloses application of EPO (erythropoietin) in preparation of a medicine for preventing and treating corneal injury, belongs to the technical field of medicines, and focuses on innovative application of EPO in preparation of the medicine for preventing and treating corneal injury. The cornea is used as a key structure of eyes and is easily damaged by various factors such as mechanical trauma, chemical injury, infection and diabetes, and more than ten millions of people in the world are troubled by cornea blindness. The invention finds that EPO has a remarkable treatment effect on corneal injury, and can promote proliferation and migration of corneal epithelium and stromal cells, increase the generation of extracellular matrix and enhance the tolerance of corneal epithelium cells and corneal stromal cells to high-level sugar. The medicine can be a self-freeze-drying preparation or a solution preparation, the administration modes are diversified, and various eye local injection, eye drop, gene therapy and the like are covered. Refined treatment schemes are provided for corneal injuries of different pathogenesis, a new way is developed for treatment of the corneal injuries, the corneal blindness rate is expected to be reduced, and the development of ophthalmic medicine is promoted.

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 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 invention provides a thymus tissue slice capable of being transplanted in vitro, a preparation method and application and a method for constructing a thymus chimeric mouse model, the thymus tissue slice is placed on a mixed cellulose ester film of hemostatic sponge, a thymus tissue slice culture medium is added, and the thymus tissue slice is continuously cultured for 5-7 days in a cell incubator with the temperature of 37 DEG C and the CO2 content of 5% to obtain the thymus chimeric mouse model. The thymus tissue slice culture medium is replaced every day in the culture process, so that thymus cells in the cultured slice are removed, thymus tissue structures and stromal cells are reserved, and the transplantable thymus tissue slice is obtained. When the thymus chimeric mouse model is constructed, the sizes of thymus tissue slices can be adjusted according to different transplantation parts, HLA matching of donors and receptors is not needed, the model construction method is simple, the transplantation success rate is high, and the model construction method can be achieved only through a small number of thymus tissue slices.

The present invention discloses a microfluidic chip and its construction method and application. A microfluidic chip of the present invention includes a polydimethylsiloxane layer and a base layer, the polydimethylsiloxane layer contains three or more microchannels; the microchannels are connected by a plurality of parallel microgrooves; the microchannels are provided with channels connected to the outside world; the base layer is at least one of a glass base, a polydimethylsiloxane base or a polystyrene base. The preparation method of the microfluidic chip of the present invention is simple and can achieve co-culture of tumor nerve cells. The pancreatic cancer-neural-stromal cell microenvironment model constructed using the microfluidic chip of the present invention can achieve the co-construction of the pancreatic cancer stromal microenvironment and the neural microenvironment, and can also perform qualitative and quantitative evaluation of nanomedicines targeting the neural microenvironment and the stromal microenvironment, which plays an important role in the screening of drugs related to the treatment of pancreatic cancer.

The present invention relates to the use of mesenchymal stem cells (MSCs) for enhancing the immune response of elderly or animal subjects to vaccination. According to the application, the defects of spleen stromal cell networks and lymphocyte structures of old subjects can be repaired by applying the MSC in advance, and the immune level of organisms is improved; and the vaccine is injected after a period of time, so that the specific antibody level after vaccine immunization can be improved. The effect can also significantly prevent the elderly subjects from being infected by influenza. Therefore, the MSC has a good application prospect in solving related immune decline of old people.

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 belongs to the technical field of biology, and provides stromal cell hydrogel as well as a preparation method and application thereof. The stromal cell hydrogel is obtained by crosslinking stromal cells modified by azido groups N3, multi-arm polyethylene glycol and polyethylene glycol N3-PEG2K-N3 modified by diazido groups. According to the invention, the stromal cells are used as a gel component for tumor organoid or 3D culture for the first time. The living cells are used as a gel material, a tumor microenvironment is highly simulated, growth factors necessary for in-vitro culture of the tumor cells are provided, and the matrix cell hydrogel truly restores an in-vivo 3D culture environment. In addition, the matrix cell hydrogel can be used for patient PDX cell culture and can be used for large-scale drug screening.

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.

The present disclosure relates to ionizable lipidoid compounds comprising an anisamide moiety, and lipid nanoparticles (LNPs) comprising the same. In certain embodiments, the LNP selectively binds to at least one sigma receptor. In certain embodiments, the LNP specifically targets a cell of interest (e.g., a cell expressing a sigma receptor, fibroblast, cancer cell, stromal cell, and epithelial cell, inter alia). In another aspect, the present disclosure provides methods for in vivo delivery of therapeutic agents to treat, prevent, and / or ameliorate diseases and / or disorders, including but not limited to fibrosis and cancer.