JP2022531582A - 細胞外小胞を高濃度で培養するための細胞培養培地及びその細胞培養培地を使用した細胞外小胞高含有馴化培養液の製造方法 - Google Patents
細胞外小胞を高濃度で培養するための細胞培養培地及びその細胞培養培地を使用した細胞外小胞高含有馴化培養液の製造方法 Download PDFInfo
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Abstract
Description
ラクトフェリン(LF)は、トランスフェリン(Tf)ファミリーであり、その配列はトランスフェリンと約60%同じである。したがって、ラクトフェリンは、その構造的特徴及び鉄イオンと結合する能力などの代表的な機能的特徴においてトランスフェリンに類似している。一方、ラクトフェリンは、トランスフェリンとは等電点が異なるため、表面の正電荷の程度が異なるためイオン結合能力が異なり、ファミリーが結合する受容体も異なる(Biochem Cell Biol. 2002; 80(1):27-34)。生成される細胞外小胞の量に対するこれらの違いを示すラクトフェリン及びトランスフェリンの効果は、酵素結合免疫沈降分析法(ELISA)を使用して確認し、細胞外小胞マーカーであるCD81とアポトーシス小胞(apoptotic vesicle)の生成程度は、マーカーであるカルネキシンで観察した。
細胞内のカルシウム濃度の増加は、細胞外小胞の生成増加に直接関係している。細胞内カルシウムの増加は、細胞膜タンパク質の非対称性を対称的に転換させ、バランスを維持する膜を破壊する(Physiology (Bethesda) 2005 Feb; 20:22-7)。細胞内カルシウム濃度の増加は、エンドソームにおける管腔内小胞(Intraluminal vesicle)の生成を増加させることも知られている。
ラクトフェリンの濃度による培養液中の細胞外小胞の数とサイズの変化を観察するために、ナノ粒子追跡分析(NTA)を行った。
血清代替剤は、トランスフェリンによる細胞外小胞の生成に影響を与えるが、栄養の供給による活発な代謝は細胞の増殖を増加させ、細胞外小胞の生成を増加させる。ラクトフェリン+カルシウム組成物が、細胞増殖又はアポトーシス物質の増加ではなく、細胞ごとに発現される細胞外小胞の生成能力を明らかに増加させることを証明するために、実験を準備した。
Claims (10)
- ラクトフェリンを含む、細胞外小胞を高濃度で培養するための細胞培養培地。
- ラクトフェリンが、0.1μg/mL~1mg/mLの濃度で含まれる、請求項1に記載の細胞培養培地。
- ラクトフェリンが、Holo-ラクトフェリン、Apo-ラクトフェリン及びPis-ラクトフェリンからなる群より選択される、請求項1に記載の細胞培養培地。
- カルシウムがさらに添加される、請求項1に記載の細胞培養培地。
- カルシウムが、0.2μM~10mMの濃度で添加される、請求項4に記載の細胞培養培地。
- 無添加培地、血清代替剤及び血清からなる群より選択される少なくとも1つの物質がさらに添加される、請求項1に記載の細胞培養培地。
- ヒトまたは動物由来の細胞に適用される、請求項1に記載の細胞培養培地。
- 細胞を請求項1~7のいずれか一項に記載の細胞培養培地で培養することを含む、細胞外小胞を高濃度で含有する馴化培養液の製造方法。
- 馴化培養液中の細胞外小胞の数が、1.0×108/mL~1.0×1011/mLの範囲である、請求項8に記載の製造方法。
- 細胞培養培地の使用が、細胞培養中の特定の時点に設定されず、繰り返し使用される、請求項8に記載の製造方法。
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KR1020190055184A KR102132457B1 (ko) | 2019-05-10 | 2019-05-10 | 세포외 소포를 고농도로 배양하기 위한 세포 배양배지 및 상기 세포 배양배지를 이용한 세포외 소포 고 함유 조건화 배양액의 제조방법 |
PCT/KR2020/003126 WO2020230990A1 (ko) | 2019-05-10 | 2020-03-05 | 세포외 소포를 고농도로 배양하기 위한 세포 배양배지 및 상기 세포 배양배지를 이용한 세포외 소포 고 함유 조건화 배양액의 제조방법 |
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