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Application of hydrogen sulfide modified mesenchymal stem cells (MSCs) extracellular vesicles (EVs) serving as miRNA delivery vector to hypoxic-ischemic brain damage (HIBD)

A delivery carrier, hypoxia-ischemia technology, applied in the field of molecular diagnosis and molecular biology, which can solve the problems of cell uptake limitation, insufficient stability, adverse immune response, etc.

Active Publication Date: 2020-02-11
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it is worth noting that factors such as insufficient in vivo stability and poor cellular uptake limit the clinical application of miRNAs.
Although several methods have been developed, such as hydrodynamic injection, viral vectors, liposomes, and nanocarriers, to deliver miRNAs, these methods have side effects such as vector toxicity, low delivery efficiency, and adverse immune responses

Method used

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  • Application of hydrogen sulfide modified mesenchymal stem cells (MSCs) extracellular vesicles (EVs) serving as miRNA delivery vector to hypoxic-ischemic brain damage (HIBD)
  • Application of hydrogen sulfide modified mesenchymal stem cells (MSCs) extracellular vesicles (EVs) serving as miRNA delivery vector to hypoxic-ischemic brain damage (HIBD)
  • Application of hydrogen sulfide modified mesenchymal stem cells (MSCs) extracellular vesicles (EVs) serving as miRNA delivery vector to hypoxic-ischemic brain damage (HIBD)

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preparation example Construction

[0043] The H 2 The preparation method of S-EVs comprises: adding sodium hydrosulfide (NaHS) into the culture medium of bone marrow mesenchymal stem cells for incubation, and collecting extracellular vesicles secreted by the bone marrow mesenchymal stem cells.

[0044] The second aspect of the present invention is to provide a composition comprising extracellular vesicles isolated from the conditioned medium of stem cells; the conditioned medium is preferably the conditioned medium of adult stem cells, more preferably The conditioned medium of mesenchymal stem cells (MSCs), such as the conditioned medium of bone marrow mesenchymal stem cells, the extracellular vesicles of the claimed composition preferably comprise miR-7.

[0045] The above composition can be used to treat hypoxic-ischemic brain injury; more specifically, it has at least one or more of the following uses:

[0046] (a) reducing brain edema induced by hypoxic-ischemic brain damage;

[0047] (b) reducing cerebra...

Embodiment

[0062] After hypoxic-ischemic (HI) brain injury (hypoxic-ischemic brain damage, HIBD) in neonatal mice, the expression of miR-7b-5p in the brain tissue of the injured side was detected at different time points, and it was found that the The expression of miR-7b-5p in brain tissue continued to decrease. At the same time, we performed high-throughput genome sequencing of two EVs, and we found that compared with EVs, H 2 Among the miRNAs of S-EVs, 19 were significantly up-regulated and 7 were significantly down-regulated. The expression of miR-7b-5p was the highest among the up-regulated miRNAs. At present, the existing technical means can modify the miRNA in EVs through pretreatment or genetic engineering to meet the needs of treating different diseases, but the use of viruses or liposomes to transfect cells has problems such as cytotoxicity, cumbersome operation, and high cost. while H 2 S treatment has the advantages of low cost, simple treatment method, and low cytotoxicit...

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Abstract

The invention provides application of hydrogen sulfide modified mesenchymal stem cells (MSCs) extracellular vesicles (EVs) serving as a miRNA delivery vector to hypoxic-ischemic brain damage (HIBD). According to the application, it is discovered and proved by first research that the curative effect of miR-7b-5p in HIBD can be effectively improved by adopting H2S to pretreat MSCs EVs. Specifically,through research, it is found that H2S-EVs can be adopted to serve as a natural excellent vector of miR-7b-5p, and exerts the better neuroprotection effect in HIBD; and meanwhile, by inhibiting expression of a target gene FOS, HI-induced brain damage and related neuroinflammation can be effectively relieved.

Description

technical field [0001] The invention belongs to the technical fields of molecular diagnosis and molecular biology, and in particular relates to the application of hydrogen sulfide-modified mesenchymal stem extracellular vesicles as miRNA delivery carriers in hypoxic-ischemic brain injury. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] Neonatal hypoxic-ischemic encephalopathy (hypoxic-ischemic encephalopathy, HIE) is due to perinatal asphyxia caused by hypoxic-ischemic (hypoxic-ischemic, HI) damage to the brain, leading to neonatal death and survivors Common disease of long-term neurological dysfunction. HIE is a serious condition with a high incidence rate. The inciden...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/46A61K31/7105A61K48/00A61P9/10A61P25/00
CPCA61K9/1271A61K31/7105A61K47/46A61P9/10A61P25/00
Inventor 王贞刘德祥初锡丽辛丹清
Owner SHANDONG UNIV
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