20 results about "Apoptotic body" patented technology

The present invention provides compositions and methods for inducing antigen-specific tolerance in a subject. In one embodiment, the present invention provides a composition comprising an apoptotic body and an epitope of an antigen. Also provided herein are methods of preparing and administering the composition. The composition and methods provided herein can induce antigen-specific tolerance in a subject.

This invention relates to biomimetic mineralized exosomes for programmed drug penetration in tumors that inhibit cell burial, along with their preparation method and applications. Belonging to the field of novel excipients and dosage forms for pharmaceutical formulations, this invention co-loads the small-molecule chemotherapeutic drugs 10-hydroxycamptothecin and banoanthraquinone into exosomes. Then, through a biomimetic mineralization strategy, aTIM-4 is organically combined with mineralized calcium phosphate particles to obtain biomimetic mineralized exosomes. Under the acidic response of the tumor microenvironment, the calcium phosphate shell dissolves, and the exosome nucleus enters the tumor cells, inducing cell death and generating apoptotic bodies. This programmatically delivers the drug, delivering banoanthraquinone deep into the tumor. Simultaneously, the released aTIM-4 inhibits the cell burial of tumor-associated macrophages, amplifying the programmed drug penetration based on apoptotic bodies. This invention provides a new strategy and more options for overcoming the bottleneck of nanomedicine penetration in tumors, meeting the urgent clinical need for highly effective chemotherapeutic agents.

The invention relates to the technical field of biological medicines, and discloses application of a ZBP1 inhibitor in preparation of a medicine for treating cognitive impairment caused by plastics. Research finds that exposure of a specific dose of nano plastic can activate a ZBP1 signal channel in an organism and promote assembly of a pan-apoptosis small body compound, so that pan-apoptosis cascade reaction with pyroptosis, apoptosis and necrosis characteristics is triggered, and finally hippocampal neuron damage, dysfunction and learning and memory ability decline are caused. Further research shows that expression of key protein of pan-apoptosis can be remarkably inhibited through local injection of the ZBP1 inhibitor to the hippocampus, cognitive function impairment induced by nano-plastics is effectively improved, and the key effect of ZBP1 serving as a core factor in the regulation and control process is defined. Based on the discovery, the ZBP1 inhibitor can be used for preparing the medicine for treating the plastic pollution related cognitive impairment, and a brand new treatment strategy is provided for clinical intervention of the diseases.

The application discloses a kind of bioengineered apoptotic bodies based on apoptotic body membrane protein and liposome and preparation method and application thereof.The bioengineered apoptotic bodies are formed by the chimerization of apoptotic body membrane protein and liposome loaded with gastrodin and Cy5.The bioengineered apoptotic bodies simulating the natural apoptosis process of mesenchymal stem cells can promote the polarization of microglial cells to M2 type, release anti-inflammatory factors and neurotrophic factors, promote the proliferation of neurons, improve the antioxidant capacity of cells, improve the nervous motor function, relieve brain edema, and thus effectively treat traumatic brain injury.

Compositions of matter, devices, and treatment protocols for reducing deleterious effects of senescent cells in a mammal. The invention provides extracorporeal devices capable of removing, in some cases selectively, senescence associated factors including small molecules, proteins, lipoproteins, as well as in some embodiments extracellular vesicles including exosomes, apoptotic bodies, or cellular released particles. Extracorporeal removal of senescent cell associated factors is performed to augment effects of senolytic therapy. Removal of senescence associated factors is performed to enhance efficacy of regenerative medicine interventions.

The invention discloses a phosphatidylserine modified gliadin nanoparticle as well as a preparation method and application thereof. The phosphatidylserine modified gliadin nanoparticle is of a core-shell structure, gliadin is entrapped by polylactic acid-glycolic acid copolymer to serve as a core, and a lipid composite membrane formed by phosphatidylserine and DSPE-PEG2000 is coated outside the nanoparticle. The gliadin-loaded nanoparticles modified by phosphatidylserine are used for simulating membrane signal characteristics of apoptotic bodies, enhancing recognition and uptake of the nanoparticles by macrophages and inducing tolerance phenotypic transformation of the nanoparticles, so that immune tolerance of celiac disease patients to gliadin is recovered, and the gliadin-loaded nanoparticles can be used for treating celiac disease patients. On the basis of simplifying the preparation process, the problems of unstable tolerance effect and lack of metabolic regulation in the existing nano immunotherapy are further solved. The nano-particles prepared by the technical route have good particle size distribution and stability, can effectively deliver antigens and induce immune tolerance, and are a novel convertible celiac disease treatment nano-preparation.

The invention relates to the technical field of biological medicine, in particular to an efficient macrophage targeting vesicle system as well as a preparation method and application thereof. The vesicle system is a chimeric vesicle (mHEs), and is prepared from extracellular vesicles (M2-EVs) derived from M2 type macrophages and apoptotic small bodies (MSC-ABs) derived from bone marrow mesenchymal stem cells. The vesicle system provided by the invention can realize specific recognition and functional regulation of macrophages, thereby playing an efficient therapeutic role in pathological processes such as tissue inflammation repair, myocardial infarction, ischemia-reperfusion injury and immune metabolism remodeling.

The invention discloses an extraction method and application of membranous small vesicles. The extraction method comprises the following steps: collecting a biological sample, and selecting at least one of blood, urine and cell culture supernatant; centrifuging the sample at 10,000 xg for 20 minutes, and removing cell debris and apoptotic bodies to obtain a pretreated sample; adding 20% by volume of sample separation liquid and CD63 / CD81 antibody modified magnetic beads into the pretreated sample, and incubating and capturing target vesicles; freezing the captured vesicles with liquid nitrogen for 15-35 minutes, and dissolving the vesicles with a 33-43 DEG C water bath; and cracking the dissolved vesicles with 0.5 W / cm < 2 > ultrasonic waves to finally obtain the intact vesicles of 30-70 nm and soluble protein factors. Original plasma or urine can be directly treated, dilution is not needed, and loss of a target object is avoided; a low-cost and degradable biomimetic polymer is developed to replace an imported kit, and the cost is reduced by 75%; the whole process lt; the time is 2.5 hours, which is superior to that of an ultracentrifugation method; and the extracted membranous small vesicles have good integrity and are suitable for liquid biopsy and drug carrier construction.

The invention relates to the technical field of biological tissue engineering, in particular to a young mesenchymal stem cell-derived apoptotic body as well as a preparation method and application thereof. The apoptotic body is formed by inducing apoptosis of young mesenchymal stem cells through staurosporine. The apoptotic body can reduce the expression level of senescence-related factors and promote expression of matrix synthesis-related factors, so that a degeneration microenvironment is improved, extracellular matrix synthesis is promoted, and cell functions are improved. The apoptotic body can be applied to the field of delaying and reversing intervertebral disc degeneration, promotes repair and regeneration of intervertebral disc tissues by delivering rejuvenation signals, provides a new cell-free treatment strategy for treatment of intervertebral disc degeneration, avoids the risks of low cell survival rate, immunological rejection, tumorigenicity and the like, and has a good application prospect. Meanwhile, the traditional limitation of recovering tissue functions through physical or medicine means is broken through.

The application belongs to the technical field of biological medicine, and discloses a kind of high-efficiency vascular endothelial cell targeting vesicle system, which is prepared by hemangioma stem cell-derived exosome HemSCs-Exos and bone marrow mesenchymal stem cell-derived apoptotic body BMSCs-ABs, and the application further discloses a preparation method of the vesicle system and its application in promoting endothelial cell proliferation and migration. Unlike existing targeted modification, the ingenious targeting relationship between BMSCs-ABs and endothelial cells in the application belongs to the combination of non-special modification, which is simple and efficient. The fusion between double EVs has the characteristics of "1+1>2", which not only retains the therapeutic components of HemSCs-Exos and BMSCs-ABs, but also has a significant cell-specific distribution after fusion. The fusion method is simple and stable.

This invention discloses a mitochondrial micro / nanoreactor system, its preparation method, and its applications. The system comprises mitochondrial-trained apoptotic bodies and a piezoelectric short-fiber scaffold, which are covalently linked via a copper-free click chemical linker. The mitochondrial-trained apoptotic bodies are obtained by inducing apoptosis in macrophages overexpressing Miro1 protein and pretreated with hypoxia, and are rich in functional mitochondria. The piezoelectric short-fiber scaffold is obtained by electrospinning a composite of poly-L-lactic acid and collagen, and can convert external mechanical energy into electrical signals. This invention, through synergistic action, on the one hand, utilizes apoptotic bodies to target and deliver functional mitochondria, enhancing intercellular mitochondrial transfer; on the other hand, it utilizes the piezoelectric effect to generate endogenous electrical stimulation, activating the mitochondrial autophagy pathway, thereby bidirectionally regulating mitochondrial energy metabolism homeostasis in diabetic wounds and significantly promoting wound healing.

In the body, adipose tissue is comprised of adipocytes as well as various other cell types, including immune cells, that may contribute to the overall extracellular vesicle pool. Adiponectin, a protein hormone produced by fat cells, and fatty acid binding protein 4 (FABP4) were selected as markers to isolate adipocyte- specific EVs / adipomes from the total pool of white adipose tissue-derived EVs based on in vitro data showing that they colocalized with Annexin V, an apoptosis marker, on the surface of budding apoptotic bodies. Intact L-adipomes (large- adipomes) and S-adipomes (small-adipomes) were successfully and selectively enriched from large-EVs and small-EVs, respectively. Immunoblotting analysis confirmed the presence of adiponectin, FABP4, Annexin V, and perilipin in both L- and S-adipomes, providing further evidence of their adipocyte origin.

Embodiments of the disclosure include treatments of subconcussive and / or concussive brain damage by administering fibroblasts and / or fibroblasts cultured with one or more types of immunocytes. In one specific embodiment fibroblasts are cultured with monocytes in the presence of patient-specific T cells, and subsequently the T cells are re-administered into the patient. In one particular embodiment, products derived from fibroblast-immunocyte mixtures are comprised of cellular lysate, apoptotic bodies, exosomes, and / or other microvesicles. In one embodiment, the fibroblast cells and / or products derived from the fibroblast cells are administered subsequent to one or multiple head injuries. In other embodiments, products are administered in combination with neurorestorative and / or neuroprotective interventions.

The application relates to the fields of biological medicine and tissue engineering materials, and particularly discloses a Janus microneedle capable of promoting inflammation subsiding and blood vessel regeneration of a diabetic wound surface as well as a preparation method and application of the Janus microneedle, the microneedle is a double-layer structure, the upper layer is loaded with an SLC7A11 inhibitor and an apoptotic body, and the lower layer is loaded with an engineered exosome overexpressing miR-17-5p. Through a unique double-layer hydrogel matrix design and a two-phase crosslinking process, the Janus microneedle realizes rapid release of active ingredients in the upper layer in the early healing stage to promote inflammation subsiding and phagocytosis, and slow release of active ingredients in the lower layer in the middle and late healing stage to continuously promote angiogenesis. The microneedle patch can intelligently simulate and synergistically regulate the natural timing of wound healing, solves the problem of space-time disconnection of the existing single therapy, and provides a novel and precise delivery strategy for efficient repair of chronic and difficult-to-heal wounds such as diabetes.

The invention provides an exosome extraction method and prepared exosome freeze-dried powder, and belongs to the technical field of exosome extraction. The invention provides an exosome extraction method which comprises the following steps: firstly, performing high-temperature stimulation on cells to improve secretion and release of exosomes; then the blood platelets subjected to high-temperature stimulation are subjected to circulating freeze thawing, so that most of cells, vesicles and the like are broken, and the integrity of the target product exosome is reserved; and filtering to remove impurities such as cell debris, apoptotic bodies and the like, and retaining an exosome product of 50-150nm. The invention also provides exosome freeze-dried powder which is prepared by freeze-drying the exosome product, and the purity of the exosome freeze-dried powder can reach 70-80%. By utilizing the exosome extraction method disclosed by the invention, the capacity of the exosome can be remarkably improved, and the method disclosed by the invention can be used for removing most impurities and retaining the integrity and activity of the exosome, so that the purity of the prepared exosome product is improved.

The invention discloses a drug loading system based on natural apoptotic bodies (AB) and application of the drug loading system in glioma photodynamic therapy. The drug loading system contains apoptotic bodies modified by targeted peptide MFGM, and the amino acid sequence of the targeted peptide MFGM is shown as SEQ ID NO. 2. Preferably, the drug loading system also contains 5-aminolevulinic acid (5-ALA). According to the invention, a drug with a relatively high concentration is directly wrapped in the MFGM modified AB, on one hand, ANG2 and RGD in the MFGM can enhance BBB penetration and tumor targeting, on the other hand, consumption of the drug and generation of by-products are also avoided, and on the other hand, the MFGM modified AB transfers the target drug into target cells through a membrane fusion effect, so that the limitation of transmembrane transport of some drugs is overcome, and the drug delivery efficiency is improved. And the concentration of the drug in target cells is enhanced. Meanwhile, for some drugs with relatively strong side effects, AB limits the drugs in vesicles for transportation, and has no toxicity to normal cells and low side effects.

In the body, adipose tissue is comprised of adipocytes as well as various other cell types, including immune cells, that may contribute to the overall extracellular vesicle pool. Adiponectin, a protein hormone produced by fat cells, and fatty acid binding protein 4 (FABP4) were selected as markers to isolate adipocyte-specific EVs / adipomes from the total pool of white adipose tissue-derived EVs based on in vitro data showing that they colocalized with Annexin V, an apoptosis marker, on the surface of budding apoptotic bodies. Intact L-adipomes (large-adipomes) and S-adipomes (small-adipomes) were successfully and selectively enriched from large-EVs and small-EVs, respectively. Immunoblotting analysis confirmed the presence of adiponectin, FABP4, Annexin V, and perilipin in both L- and S-adipomes, providing further evidence of their adipocyte origin.

The invention relates to a double-layer detachable microneedle which comprises a soluble microneedle tip and a detachable hydrogel substrate layer, and the microneedle tip layer comprises at least one of drugs, extracellular vesicles, macromolecular substances and combinations of the drugs, the extracellular vesicles and the macromolecular substances. The extracellular vesicles are one or a combination of a plurality of exosomes, microvesicles, apoptotic bodies, autophagy-related extracellular vesicles, matrix vesicles and stress-related extracellular vesicles, and the macromolecular substances are one or a combination of a plurality of polypeptides, proteins, antigens, enzymes and antibodies. According to the double-layer detachable microneedle, early-stage antibiosis and pH adjustment can be achieved, infection is reduced, and inflammation is inhibited; macrophages are induced to be polarized from M1 to M2, and inflammation is promoted to be transited to a proliferation stage; needle tip loading is continuously released, and angiogenesis, cell proliferation and tissue regeneration are enhanced; the double-layer structure can sequentially respond to different stage requirements of the wound, and the healing efficiency of the diabetic wound is remarkably improved.

The present application relates to a kind of engineered stem cell nanometer apoptotic bodies, its preparation method includes the following steps: by 3,3'-diindolylmethane directional induction obtains the engineered stem cell rich in repair and anti-inflammatory signal molecules, and then the engineered stem cell is induced to apoptosis, and the supernatant is separated and obtained by collection, then the programmed tandem extrusion process is handled to the engineered apoptotic body, and the particle size uniformity of the engineered nanometer apoptotic body is prepared.The engineered nanometer apoptotic body of the present application can effectively improve the microenvironment around hair follicle and regulate hair growth cycle, significantly improve the hair density and regeneration rate of androgenetic alopecia model mice, provide a new strategy of safe, convenient and efficient for clinical hair regeneration treatment.

The invention provides an adipose-derived stem cell apoptotic body as well as a preparation method and application thereof, and belongs to the technical field of medicines. The preparation method comprises the following steps: step (1), obtaining adipose-derived stem cells by a type I collagenase digestion method, and culturing in vitro to an induction period; and (2) taking the adipose-derived stem cells in the induction period, inducing concentrated apoptosis by an STS method, adding trypsin for digestion, and carrying out differential centrifugation at room temperature to obtain a precipitate, namely the adipose-derived stem cell apoptotic body. It is found for the first time that the adipose-derived stem cell apoptotic body has the effect of inhibiting CDC20 expression in hypertrophic scar fibroblasts so as to reduce Wnt / beta-catenin signal channels, and meanwhile, the adipose-derived stem cell apoptotic body has the remarkable inhibiting effect on pathological phenotypes and transverse migration of the hypertrophic scar-derived fibroblasts. In addition, the method is simple to operate, low in cost, safe, efficient and convenient for clinical popularization and application.