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Composition including stem cell-derived microvesicles for promoting neurogenesis

Inactive Publication Date: 2015-02-12
SAMSUNG LIFE PUBLIC WELFARE FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about stem cell-derived microvesicles that can promote the growth and movement of nerve cells and promote the formation of new blood vessels, making them useful for treating neurological damage.

Problems solved by technology

Moreover, it is known, as a result of clinical studies up to now, that stem cell therapies have not yet shown a significant effect.
Extensive research on a variety of genetically modified stem cells to promote the effect has continued to progress, but cell therapies using genes cannot be applied to the human body due to ethical issues.
Moreover, there are several problems in clinical application of the use of stem cells.
Firstly, in the case of cell therapy products, there is a risk of tumor formation after stem cells are transplanted into tissue.
Secondly, stem cells may cause arterial occlusion due to a relatively large size, resulting in cerebral infarction.
Thirdly, stem cells can migrate to the brain during the acute phase when the brain-blood barrier is open but have limitations in crossing the brain-blood barrier due to a large size during the chronic stage.
Lastly, inducing stem cells to specialized cells having desired properties for cell therapy products has limitation.
However, there is not much research on stem cell-derived microvesicles, and it cannot be said that all stem cells that can be used for treatment of various diseases can be replaced by microvesicles.

Method used

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  • Composition including stem cell-derived microvesicles for promoting neurogenesis
  • Composition including stem cell-derived microvesicles for promoting neurogenesis
  • Composition including stem cell-derived microvesicles for promoting neurogenesis

Examples

Experimental program
Comparison scheme
Effect test

example 1

Comparison of the levels of Stem Cell-Derived Microvesicles in Serum

[0047]Citrated sera were collected from stroke patients and centrifuged at 19,800 g and 10° C. for 10 minutes to obtain stem cell-derived microvesicles. The obtained stem cell-derived microvesicles were suspended in 20 μl PBS, and the blood levels of stem cell-derived microvesicles (CD105-positive / annexin V-negative) and microvesicles (CXCR4-positive / annexin V-negative) expressing the SDF-1 receptor, CXCR4, were compared in patients with a small infarct (DWI volume: 10 cc or less) and patients with a large infarct (DWI volume: 10 cc or more), and it was determined whether CD105-positive cells were CD90-positive or double-positive cells. The results of the above experiment are shown in FIG. 1.

[0048]As shown in FIG. 1, it was found that the amount of CD105-positive cells and CXCR4-positive cells in patients with a large infarct (B) after the onset of cerebral infarction was greater than that in patients with a small ...

example 2

Isolation of Microvesicles from Bone Marrow-Derived Stem Cells

2.1 Collection and Culture of Mesenchymal Stem Cells

[0051]Bone marrows were collected from the femur of rats to obtain bone marrow-derived mesenchymal stem cells by culture. The obtained mesenchymal stem cells were cultured at a density of 1×105 cell / ml in T75 flask at 5% CO2 and 37° C. and subcultured at 80% confluence. The subculture was performed in a manner that the medium was removed, the stem cells were gently washed with PBS more than once, cultured in a 37° C. incubator for about 1 minute after addition of Tryple (Invitrogen), and placed in a medium containing 10% FBS fetal bovine serum (FBS) to neutralize the reaction, and then the cells were collected and centrifuged at 1,300 g for 4 minutes. The cell precipitates were resuspended in a medium containing FBS, counted, and cultured. The fourth to sixth passage cells were used in the experiment. Low-glucose DMEM containing 10% PBS and 1% penicillin / streptomycin was...

example 3

Stimulation of Neural Stem Cells using Stem Cell-Derived Microvesicles

3.1 Isolation and Culture of Neural Stem Cells

[0058]Brain tissues collected from 14-day-old embryonic rats were gently fragmented using a narrow-bore glass pipette or dissociated to single cell level using a cell dissociation solution such as Accutase and centrifuged (500 g, 5 minutes), thus obtaining precipitated cells. The obtained cells were cultured in DMEM / F12 medium containing 1XN2 supplement, 25 ng / ml bFGF, and 25 ng / ml EGF to induce neural stem cells. The induced neural stem cells were subcultured such that the diameter of the neuronal cell is maintained within 100 rim.

3.2 Increase in Neurogenesis Capability of Neural Stem Cells by Stem Cell-Derived Microvesicles

[0059]The neural stem cells induced in Example 3.1 were treated with the stem cell-derived microvesicles obtained in Example 2.3 by ischemic preconditioning, and the neurogenesis capabilities of the treated neural stem cells were compared. Microves...

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Abstract

The present invention relates to a composition including stem cell-derived microvesicles as an active ingredient for promoting neurogenesis. The stem cell-derived microvesicles according to the present invention can promote neurogenesis and migration of nerves and also promote angiogenesis in vascular endothelial cells, and thus can be usefully used in treatment of neurological damage.

Description

TECHNICAL FIELD[0001]The present invention relates to a composition comprising stem cell-derived microvesicles for promoting neurogenesis and a method for promoting neurogenesis.BACKGROUND ART[0002]Recently, various preclinical and clinical studies on stem cell therapies have been conducted for various diseases such as cerebral infarction, traumatic neuronal injury, musculoskeletal disease, etc. However, the current technology has reached up to the level of simple extraction, culture and proliferation of stem cells and injection of the stem cells. Moreover, it is known, as a result of clinical studies up to now, that stem cell therapies have not yet shown a significant effect. Extensive research on a variety of genetically modified stem cells to promote the effect has continued to progress, but cell therapies using genes cannot be applied to the human body due to ethical issues.[0003]Moreover, there are several problems in clinical application of the use of stem cells. Firstly, in t...

Claims

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Application Information

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IPC IPC(8): A61K35/28A61K38/17A61K35/12A61K35/51
CPCA61K35/28A61K38/1793A61K38/179A61K35/12A61K35/51A61P9/00A61P9/10A61P25/00A61P25/08A61P25/16A61P25/28C12N5/0623C12N5/069C12N2502/11C12N2502/1358A61K35/44
Inventor BANG, OH YOUNGMOON, GYEONG JOONCHO, YEON HEEKIM, SUK JAEKIM, DONG HEESUNG, JI HEE
Owner SAMSUNG LIFE PUBLIC WELFARE FOUND
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