JP2019535757A - 脂肪幹細胞由来のエキソソームを有効成分として含む肝線維症予防または治療用の組成物 - Google Patents
脂肪幹細胞由来のエキソソームを有効成分として含む肝線維症予防または治療用の組成物 Download PDFInfo
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Abstract
Description
ヒト脂肪幹細胞からエキソソームを抽出するために、前記ヒト脂肪幹細胞を DMEM(Dulbecco’s Modified Eagle Medium)培地(Gibco,Cat#:11995065)で培養し、エキソソームの抽出24時間前に、血清、抗生剤及びフェノールレッド(phenol red)が含まれていないDMEM培地(Gibco Cat#:31053028)に替えて24時間培養した。
前記実施例1で抽出したエキソソームが、実際の肝線維化の過程で肝損傷によって活性化し、コラーゲン及び肝線維化因子などの放出に大きく関与すると知られたヒト肝星細胞(human hepatic stellate cell)に及ぼす影響を確認するために、関連細胞株であるLX−2を用いて抗線維化効能の評価を行った。
本発明によるヒト脂肪幹細胞由来のエキソソームがヒト他組織幹細胞由来のエキソソームに比べて抗線維化効果に優れることを比較実験するために、実験群として、ヒト骨髓幹細胞(Bone−marrow stem cell exosome:B−エキソソーム)と、ヒト臍帯幹細胞(Umbilical−cord stem cell exosome:U−エキソソーム)から各々抽出されたエキソソームを製造し、前記実施例2の免疫蛍光及びリアルタイムPCRによって比較評価した。
ヒト脂肪幹細胞由来のエキソソームの生体内分布挙動を評価するために、正常モデルと肝線維症誘発マウスモデルにDiR;1,1’−ジオクタデシル−3,3,3’,3’−テトラメチルインドトリカルボシアニンヨージド(1,1’−Dioctadecyl−3,3,3’,3’−Tetramethylindotricarbocyanine Iodide)蛍光物質で標識されたヒト脂肪幹細胞由来のエキソソームを、培養液100μLに分散させてしっぽ静脈に注射した。それから24時間後、各々の集団のマウスを解剖して主要臓器を摘出してその蛍光を確認した。
前記実施例1のヒト脂肪幹細胞由来のエキソソームを用いて実際の肝線維症動物モデルにおいて抗線維化の効果があるかを確認し、ヒト脂肪幹細胞(Adipose Derived Stem Cells,ADSC)よりもヒト脂肪幹細胞由来のエキソソーム(A−エキソソーム)を投与した場合、肝の機能がさらに効果的に改善したことを確認した。
Claims (7)
- 脂肪幹細胞由来のエキソソームを有効成分として含む、肝線維症の予防または治療用の薬学的組成物。
- 前記脂肪幹細胞が、ヒト脂肪幹細胞であることを特徴とする請求項1に記載の薬学的組成物。
- 前記薬学的組成物が、血中アスパラギン酸アミノ基転移酵素(AST)、血中アラニンアミノ基転移酵素(ALT)、アルカリホスファターゼ(ALP)、総ビリルビン(TB)またはLW/BWの水準を減少させることを特徴とする請求項1に記載の薬学的組成物。
- 脂肪幹細胞由来のエキソソームを有効成分として含む薬学的組成物を個体に投与する段階を含む、肝線維症の予防または治療方法。
- 脂肪幹細胞由来のエキソソームの、肝線維症の予防または治療用途。
- 脂肪幹細胞由来のエキソソームを有効成分として含む、肝線維症改善用の健康機能食品組成物。
- 前記脂肪幹細胞が、ヒト由来の脂肪幹細胞であることを特徴とする請求項6に記載の健康機能食品組成物。
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KR1020170154641A KR20180057546A (ko) | 2016-11-21 | 2017-11-20 | 지방줄기세포유래 엑소좀을 유효성분으로 포함하는 간 섬유증 예방 또는 치료용 조성물 |
KR10-2017-0154641 | 2017-11-20 | ||
PCT/KR2017/013255 WO2018093233A1 (ko) | 2016-11-21 | 2017-11-21 | 지방줄기세포유래 엑소좀을 유효성분으로 포함하는 간 섬유증 예방 또는 치료용 조성물 |
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KR20210100449A (ko) | 2020-02-06 | 2021-08-17 | 성균관대학교산학협력단 | 줄기세포 유래의 엑소좀의 동결건조 제제 |
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