JP2022113744A - 軟骨細胞適用のための脂肪細胞 - Google Patents
軟骨細胞適用のための脂肪細胞 Download PDFInfo
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Abstract
Description
vivoでの送達の際の軟骨の安定化のための1つまたは複数の支持体を含む。
本開示の方法によって、任意の軟骨組織などの、任意の組織を少なくとも一部修復することができるが、特定の例示的実施形態においては、椎間板軟骨または関節軟骨が修復される。本開示の一般的実施形態は、椎間板のための新しい軟骨を操作するための細胞供給源として脂肪細胞を使用することである。本開示は、これらの細胞の軟骨細胞様細胞への分化を包含する。
本開示のある特定の実施形態においては、細胞が軟骨細胞または軟骨細胞様細胞に分化することができる限り、任意の細胞を用いることができる。しかしながら、特定の実施形態においては、前記細胞は、例えば、脂肪細胞である。自己細胞を用いることができるが、代替的な実施形態においては、同種異系細胞が用いられる;特定の実施形態においては、同種異系細胞は、疾患についてアッセイされており、ヒトへの伝達にとって好適であると考えられる。本開示のある特定の態様においては、前記細胞または複数の細胞は自己であるが、代替的な実施形態においては、細胞は同種異系である。細胞が自己ではない場合、本開示における使用の前に、当業界で標準的な手段によって細胞をプロセッシングして、潜在的に有害な材料、病原体などを除去することができる。
機械的応力/ひずみは、軟骨形成のための重要な因子である。本発明の方法は、1つまたは複数の機械的ひずみを用いる。脂肪細胞の軟骨形成性分化の誘導因子としての、間欠的静水圧(IHP)、低酸素圧、剪断流体応力、圧力負荷、またはその組合せなどの実施形態がある。本開示のいくつかの実施形態においては、細胞を、例えば、三次元マトリックス中で培養する。
本開示の特定の実施形態においては、脂肪細胞または再分化した脂肪細胞を、1つまたは複数の支持体と共に個体に送達する。細胞が組織の形態にあり、いくつかの場合、組織が所望の形状のものである場合、細胞を支持体と共に送達することができる。
脂肪細胞の注入およびin vivoでの分化
本開示の実施形態においては、脂肪細胞を哺乳動物の脊椎に送達して、例えば、椎間板変性を改善する。いくつかの実施形態においては、脂肪細胞を哺乳動物の脊椎に送達して、軟骨細胞分化を誘導するか、または軟骨細胞分化を継続する。
脂肪細胞からの軟骨のex vivoでの産生
軟骨を必要とするか、または軟骨を必要とすることが疑われる個体を、本開示の方法にかける。例えば、軟骨の欠損または欠陥を有するなどの軟骨を必要とする個体を、本開示の方法にかける。特定の実施形態においては、個体を、軟骨を必要とすると診断する。いくつかの実施形態においては、個体は、椎間板修復を必要としない。
Claims (50)
- 脂肪細胞に機械的ひずみをかけるステップを含む、脂肪細胞の軟骨細胞様細胞への脱分化を誘導する方法。
- 前記かけるステップが、in vitroまたはex vivoで行われる、請求項1に記載の方法。
- 前記かけるステップが、in vivoで行われる、請求項1に記載の方法。
- 前記機械的ひずみが、低酸素圧、間欠的静水圧、流体剪断応力、またはその組合せを含む、請求項1に記載の方法。
- 前記脂肪細胞が、白色脂肪細胞、褐色脂肪細胞、またはその混合物である、請求項1に記載の方法。
- 前記かけるステップがin vitroで行われる場合、前記細胞を足場と組み合わせて、細胞/足場組成物を産生する、請求項2に記載の方法。
- 前記細胞/足場組成物が、成長因子、マトリックス分子、薬物、またはその組合せを含む、請求項6に記載の方法。
- 前記細胞/足場組成物が、個体に送達される、請求項6に記載の方法。
- 前記細胞/足場組成物が、個体の関節に送達される、請求項8に記載の方法。
- 前記関節が、椎間板である、請求項9に記載の方法。
- 前記個体が、椎間板疾患を有する、請求項10に記載の方法。
- 前記かけるステップがex vivoで行われる場合、前記細胞に、軟骨を生成するのに好適な条件が提供される、請求項3に記載の方法。
- 前記条件が、低酸素、機械的応力、またはその組合せを含む、請求項12に記載の方法。
- 前記軟骨が、所望の形状の形態で配置される、請求項12に記載の方法。
- 前記所望の形状が、耳または鼻の少なくとも一部である、請求項14に記載の方法。
- 前記所望の形状の鋳型を作製するステップをさらに含む、請求項14に記載の方法。
- 軟骨修復を必要とする個体に前記軟骨を提供するステップをさらに含む、請求項14に記載の方法。
- 前記所望の形状が、個体の身体の1つまたは複数の領域で軟骨を置換または修復するために用いられ、ここで該領域は結合組織を必要とする、請求項14に記載の方法。
- 軟骨修復を必要とするか、または軟骨修復を必要とすることが疑われる個体の身体の一部を画像化するステップをさらに含む、請求項14に記載の方法。
- 軟骨修復を必要とする個体の身体の一部を画像化するステップと、所望の形状の軟骨の鋳型をそれから作製するステップとをさらに含む、請求項14に記載の方法。
- 個体の身体の一部を画像化するステップであって、該一部は修復を必要としない、ステップと、該画像を使用して、修復を必要とする領域を置換または修復するために軟骨を成長させるための鋳型を作製するステップとをさらに含む、請求項14に記載の方法。
- 前記軟骨が、1つまたは複数の支持体を用いて前記個体に提供される、請求項17に記載の方法。
- 前記支持体が、再吸収性である、請求項22に記載の方法。
- 前記支持体が、軟骨形成中および/またはその機能が完了した後に、前記個体の身体により再吸収される材料から構成される、請求項22に記載の方法。
- 前記支持体が、非再吸収性である、請求項22に記載の方法。
- 前記支持体が、体中に残存し、前記軟骨の形状および機能を維持するための足場として作用し得る、金属または1つもしくは複数の他の材料から構成される、請求項25に記載の方法。
- 前記軟骨組織が、前記個体にとって結合組織が必要とされる、鼻、耳、膝、肩、肘または身体の他の領域に送達される、請求項17に記載の方法。
- 前記軟骨組織が、関節に送達されない、請求項17に記載の方法。
- 前記軟骨組織が、椎間板に送達されない、請求項17に記載の方法。
- 前記かけるステップがin vivoで行われる場合、該in vivoでのかけるステップの前に、成長因子、マトリックス分子、機械的ひずみ、またはその組合せを前記脂肪細胞にかけない、請求項3に記載の方法。
- 前記脂肪細胞が、前記個体の関節に送達される、請求項3に記載の方法。
- 前記個体が、椎間板疾患を有する、請求項3に記載の方法。
- 前記細胞が、椎間板に送達される、請求項3に記載の方法。
- 前記関節への送達後、前記関節中に脂肪細胞と軟骨細胞様細胞との混合物が存在する、請求項31に記載の方法。
- 前記軟骨細胞様細胞が、マトリックス分子を産生する細胞とさらに定義される、請求項34に記載の方法。
- 前記マトリックス分子が、コラーゲンI、コラーゲンII、プロテオグリカン、またはその組合せである、請求項35に記載の方法。
- 前記コラーゲンが、I型およびII型コラーゲンを含む、請求項36に記載の方法。
- 前記プロテオグリカンの1つが、アグリカンである、請求項36に記載の方法。
- 前記脂肪細胞が、椎間板の間に送達される、請求項31に記載の方法。
- 前記脂肪細胞が、髄核と線維輪内部の亀裂との間、またはその中に送達される、請求項31に記載の方法。
- 前記個体から脂肪細胞を取得することをさらに含む、請求項1に記載の方法。
- 前記取得された脂肪細胞を、拡大させる、請求項41に記載の方法。
- 前記取得された脂肪細胞を、少なくとも1日間拡大させる、請求項42に記載の方法。
- 前記取得された脂肪細胞を継代する、請求項41に記載の方法。
- 前記継代を2回以上行う、請求項44に記載の方法。
- 前記個体の関節に前記脂肪細胞を送達した後、複数の脂肪細胞が死滅する、請求項31に記載の方法。
- 前記脂肪細胞の死滅が、前記個体の内因性関節細胞からの細胞応答をもたらす、請求項46に記載の方法。
- 前記細胞応答が、前記個体の内因性関節細胞の成長の刺激を含む、請求項47に記載の方法。
- 前記個体の関節に前記脂肪細胞を送達した後、前記関節中に瘢痕組織の発達が起こる、請求項31に記載の方法。
- 前記細胞が前記個体にとって自己または同種異系である、請求項1に記載の方法。
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- 2014-06-13 CN CN201480039060.2A patent/CN105452447A/zh active Pending
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JP2016523083A (ja) | 2016-08-08 |
JP7084963B2 (ja) | 2022-06-15 |
AU2014281818B2 (en) | 2019-08-22 |
JP2020168026A (ja) | 2020-10-15 |
HK1222199A1 (zh) | 2017-06-23 |
AU2019253856A1 (en) | 2019-11-21 |
EP3011015A2 (en) | 2016-04-27 |
CN105452447A (zh) | 2016-03-30 |
US20140377231A1 (en) | 2014-12-25 |
EP3011015B1 (en) | 2021-02-24 |
AU2019253856B2 (en) | 2021-09-16 |
WO2014204806A2 (en) | 2014-12-24 |
WO2014204806A3 (en) | 2015-05-28 |
US20190142871A1 (en) | 2019-05-16 |
CA2915249C (en) | 2022-04-12 |
CA2915249A1 (en) | 2014-12-24 |
EP3011015A4 (en) | 2016-12-07 |
AU2014281818A1 (en) | 2015-12-24 |
ES2870558T3 (es) | 2021-10-27 |
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