JPWO2021200299A5 - - Google Patents

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JPWO2021200299A5
JPWO2021200299A5 JP2022511936A JP2022511936A JPWO2021200299A5 JP WO2021200299 A5 JPWO2021200299 A5 JP WO2021200299A5 JP 2022511936 A JP2022511936 A JP 2022511936A JP 2022511936 A JP2022511936 A JP 2022511936A JP WO2021200299 A5 JPWO2021200299 A5 JP WO2021200299A5
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biological tissue
tissue repair
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extracellular vesicles
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間葉系幹細胞に由来する細胞外小胞を有効成分とする、細胞老化抑制剤又は生体組織修復促進剤であって、
細胞外小胞が炎症性サイトカインにより刺激を加えた間葉系幹細胞に由来するものである、又は/及び細胞外小胞がホスファチジルセリンに対して親和性を有する物質を利用する方法により得られるものである、細胞老化抑制剤又は生体組織修復促進剤。
A cell aging inhibitor or biological tissue repair promoter containing extracellular vesicles derived from mesenchymal stem cells as an active ingredient,
The extracellular vesicles are derived from mesenchymal stem cells stimulated with inflammatory cytokines, or/and the extracellular vesicles are obtained by a method using a substance having affinity for phosphatidylserine. A cell aging inhibitor or biological tissue repair promoter.
前記間葉系幹細胞が、iPS細胞に由来するもの、或いは臍帯、臍帯血、骨髄、脂肪、筋肉、神経、皮膚、歯髄、羊膜及び胎盤からなる群より選択される1種以上の組織に由来するものである、請求項1に記載の細胞老化抑制剤又は生体組織修復促進剤。 The mesenchymal stem cells are derived from iPS cells, or from one or more tissues selected from the group consisting of umbilical cord, cord blood, bone marrow, fat, muscle, nerve, skin, dental pulp, amniotic membrane and placenta. The agent for suppressing cell senescence or the agent for promoting biological tissue repair according to claim 1, which is 前記間葉系幹細胞が、腫瘍壊死因子α、インターロイキン1、インターロイキン6、インターロイキン8、インターロイキン12、インターロイキン18及びインターフェロンγから選ばれる少なくとも1種の炎症性サイトカインにより刺激を加えたものである、請求項1に記載の細胞老化抑制剤又は生体組織修復促進剤。 The mesenchymal stem cells stimulated with at least one inflammatory cytokine selected from tumor necrosis factor α, interleukin 1, interleukin 6, interleukin 8, interleukin 12, interleukin 18 and interferon γ. The cell senescence inhibitor or biological tissue repair promoter according to claim 1, which is 前記細胞外小胞が、ホスファチジルセリンに対して親和性を有する物質を利用する方法により得られるものである、請求1に記載の細胞老化抑制剤又は生体組織修復促進剤。 2. The cell aging inhibitor or biological tissue repair promoter according to claim 1, wherein said extracellular vesicles are obtained by a method using a substance having affinity for phosphatidylserine. 前記ホスファチジルセリンに対して親和性を有する物質が、Timタンパク質である、請求項1に記載の細胞老化抑制剤又は生体組織修復促進剤。 2. The cell aging inhibitor or biological tissue repair promoter according to claim 1, wherein the substance having affinity for phosphatidylserine is Tim protein. 前記Timタンパク質が、Tim4タンパク質、Tim3タンパク質及びTim1タンパク質から選択されるものである、請求項5に記載の細胞老化抑制剤又は生体組織修復促進剤。 6. The agent for suppressing cell senescence or promoting biological tissue repair according to claim 5, wherein the Tim protein is selected from Tim4 protein, Tim3 protein and Tim1 protein. 前記細胞外小胞が、炎症性サイトカインにより刺激を加えた間葉系幹細胞に由来するものであり、且つホスファチジルセリンに対して親和性を有する物質を利用する方法により得られるものである、請求項1に記載の細胞老化抑制剤又は生体組織修復促進剤。 The extracellular vesicles are derived from mesenchymal stem cells stimulated with inflammatory cytokines and obtained by a method using a substance having affinity for phosphatidylserine. 2. Cell senescence inhibitor or biological tissue repair accelerator according to 1. 前記細胞老化抑制又は生体組織修復促進が、細胞増殖促進作用、コラーゲンの産生促進若しくは分解抑制作用、ヒアルロン酸の産生促進若しくは分解抑制作用、及びエラスチンの産生促進若しくは分解抑制作用から選ばれる少なくとも1種の作用によるものである、請求項1に記載の細胞老化抑制剤又は生体組織修復促進剤。 The cell senescence inhibition or biological tissue repair promotion is at least one selected from cell proliferation promotion action, collagen production promotion or degradation inhibition action, hyaluronic acid production promotion or degradation inhibition action, and elastin production promotion or degradation inhibition action. The cell aging inhibitor or biological tissue repair promoter according to claim 1, which is due to the action of 炎症性サイトカインにより刺激を加えた間葉系幹細胞から細胞外小胞を得ること、又は/及び間葉系幹細胞由来の細胞外小胞からホスファチジルセリンに対して親和性を有する物質を用いる方法により細胞外小胞を得ることを含む、細胞老化抑制作用又は生体組織修復促進作用を有する細胞外小胞の製造方法。 Obtaining extracellular vesicles from mesenchymal stem cells stimulated with inflammatory cytokines, or/and extracellular vesicles derived from mesenchymal stem cells by a method using a substance having affinity for phosphatidylserine A method for producing extracellular vesicles having cell senescence-inhibiting action or biological tissue repair-promoting action, comprising obtaining extracellular vesicles. 前記間葉系幹細胞が、iPS細胞に由来するもの、或いは臍帯、臍帯血、骨髄、脂肪、筋肉、神経、皮膚、歯髄、羊膜及び胎盤からなる群より選択される1種以上の組織に由来するものである、請求項9に記載の細胞老化抑制作用又は生体組織修復促進作用を有する細胞外小胞の製造方法。 The mesenchymal stem cells are derived from iPS cells, or from one or more tissues selected from the group consisting of umbilical cord, cord blood, bone marrow, fat, muscle, nerve, skin, dental pulp, amniotic membrane and placenta. 10. The method for producing extracellular vesicles having cell senescence-suppressing action or biological tissue repair-promoting action according to claim 9. 前記間葉系幹細胞が、腫瘍壊死因子α、インターロイキン1、インターロイキン6、インターロイキン8、インターロイキン12、インターロイキン18及びインターフェロンγから選ばれる少なくとも1種の炎症性サイトカインにより刺激を加えたものである、請求項9に記載の細胞老化抑制作用又は生体組織修復促進作用を有する細胞外小胞の製造方法。 The mesenchymal stem cells stimulated with at least one inflammatory cytokine selected from tumor necrosis factor α, interleukin 1, interleukin 6, interleukin 8, interleukin 12, interleukin 18 and interferon γ. The method for producing extracellular vesicles having cell senescence-suppressing action or biological tissue repair-promoting action according to claim 9. 前記細胞外小胞が、ホスファチジルセリンに対して親和性を有する物質を利用する方法により得られるものである、請求項9に記載の細胞老化抑制作用又は生体組織修復促進作用を有する細胞外小胞の製造方法。 Extracellular vesicles having cell senescence-inhibiting action or biological tissue repair-promoting action according to claim 9, wherein the extracellular vesicles are obtained by a method using a substance having affinity for phosphatidylserine. manufacturing method. 前記ホスファチジルセリンに対して親和性を有する物質が、Timタンパク質である、請求項9に記載の細胞老化抑制作用又は生体組織修復促進作用を有する細胞外小胞の製造方法。 10. The method for producing extracellular vesicles having cell senescence-inhibiting action or biological tissue repair-promoting action according to claim 9, wherein the substance having affinity for phosphatidylserine is Tim protein. 前記Timタンパク質が、Tim4タンパク質、Tim3タンパク質及びTim1タンパク質から選択されるものである、請求項13に記載の細胞老化抑制作用又は生体組織修復促進作用を有する細胞外小胞の製造方法。 14. The method for producing extracellular vesicles having cell senescence-inhibiting action or biological tissue repair-promoting action according to claim 13, wherein the Tim protein is selected from Tim4 protein, Tim3 protein and Tim1 protein. 前記細胞外小胞が、炎症性サイトカインにより刺激を加えた間葉系幹細胞に由来するものであり、且つホスファチジルセリンに対して親和性を有する物質を利用する方法により得られるものである、請求項9に記載の細胞老化抑制作用又は生体組織修復促進作用を有する細胞外小胞の製造方法。 The extracellular vesicles are derived from mesenchymal stem cells stimulated with inflammatory cytokines and obtained by a method using a substance having affinity for phosphatidylserine. 10. The method for producing extracellular vesicles having cell senescence-inhibiting action or biological tissue repair-promoting action according to 9. 前記細胞老化抑制作用又は生体組織修復促進作用が、細胞増殖促進作用、コラーゲンの産生促進若しくは分解抑制作用、ヒアルロン酸の産生促進若しくは分解抑制作用、及びエラスチンの産生促進若しくは分解抑制作用から選ばれる少なくとも1種の作用によるものである、請求項9に記載の細胞老化抑制作用又は生体組織修復促進作用を有する細胞外小胞の製造方法。 The cell aging-inhibiting action or biological tissue repair-promoting action is at least selected from cell proliferation-promoting action, collagen production-promoting or degradation-inhibiting action, hyaluronic acid production-promoting or degradation-inhibiting action, and elastin production-promoting or degradation-inhibiting action 10. The method for producing extracellular vesicles having cell senescence-inhibiting action or biological tissue repair-promoting action according to claim 9, which is based on one type of action. 間葉系幹細胞に由来する細胞外小胞を有効成分とする、遺伝子発現調節剤であって、
細胞外小胞が、炎症性サイトカインにより刺激を加えた間葉系幹細胞に由来するものである、又は/及び細胞外小胞がホスファチジルセリンに対して親和性を有する物質を利用する方法により得られるものであり、且つ
遺伝子が、細胞増殖抑制遺伝子、コラーゲン遺伝子、コラーゲン分解酵素遺伝子、ヒアルロン酸合成酵素遺伝子、ヒアルロン酸分解酵素遺伝子、エラスチン遺伝子、及びエラスチン分解酵素遺伝子から選ばれる少なくとも1種の遺伝子である、遺伝子発現調節剤。
A gene expression regulator containing extracellular vesicles derived from mesenchymal stem cells as an active ingredient,
Extracellular vesicles are derived from mesenchymal stem cells stimulated with inflammatory cytokines, or/and extracellular vesicles are obtained by a method using a substance having affinity for phosphatidylserine and the gene is at least one gene selected from a cell growth inhibitory gene, a collagen gene, a collagenase gene, a hyaluronic acid synthase gene, a hyaluronanase gene, an elastin gene, and an elastinase gene. A gene expression regulator.
請求項1~請求項8のいずれか1項に記載の細胞老化抑制剤又は生体組織修復促進剤を含有する細胞老化抑制用又は生体組織修復促進用皮膚外用組成物。 An external skin composition for inhibiting cell aging or promoting biological tissue repair, containing the cell aging inhibitor or the biological tissue repair promoting agent according to any one of claims 1 to 8.
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