JP2020519645A - 脂肪組織由来幹細胞による多発性硬化症の治療 - Google Patents
脂肪組織由来幹細胞による多発性硬化症の治療 Download PDFInfo
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Abstract
Description
(a)吸引脂肪組織を凍結するステップと、
(b)吸引脂肪組織を解凍し、組織分散酵素を用いて、又は機械的破砕により分散させるステップと、
(c)hADSCを含む細胞分画を遠心分離によってペレッティングし、任意にペレットを、細胞生存率を支持可能な懸濁培地で洗浄し、懸濁液を少なくとも1回の追加の遠心分離にかけるステップと、
(d)ステップ(c)で得られたペレットを、細胞生存率を支持可能な懸濁培地で再懸濁し、再懸濁されたペレット内の細胞集団からhADSCを選択するステップと、
(e)任意に、hADSCの選択の前に少なくとも1回濾過をおこなうステップと、
(f)任意に、hADSCを少なくとも3継代にわたって培養するステップと、
によってヒト皮下脂肪から得られたhADSCである。
(a)吸引脂肪組織を凍結するステップと、
(b)吸引脂肪組織を解凍し、組織分散酵素を用いて、又は機械的破砕により分散させるステップと、
(c)hADSCを含む細胞分画を遠心分離によってペレッティングし、任意にペレットを、細胞生存率を支持可能な懸濁培地で洗浄し、少なくとも1回の追加の遠心分離にかけるステップと、
(d)ステップ(c)で得られたペレットを緩衝液又は培養液で再懸濁し、少なくとも1回濾過をおこなうステップと、
(e)再懸濁されたペレット内の細胞集団からhADSCを選択するステップと、
(f)任意に、hADSCを少なくとも3継代にわたって培養するステップと、
(g)対象のCNSにhADSCを注入するステップと、
によってヒト皮下脂肪からhADSCを取得することを含む。
(a)吸引脂肪組織を凍結するステップと、
(b)吸引脂肪組織を解凍し、組織分散酵素を用いて、又は機械的破砕により分散させるステップと、
(c)hADSCを含む細胞分画を遠心分離によってペレッティングし、任意にペレットを、細胞生存率を支持可能な懸濁培地で洗浄し、懸濁液を少なくとも1回の追加の遠心分離にかけるステップと、
(d)ステップ(c)で得られたペレットを、細胞生存率を支持可能な懸濁培地で再懸濁し、少なくとも1回濾過をおこなうステップと、
(e)再懸濁されたペレット内の細胞集団からhADSCを選択するステップと、
(f)任意に、hADSCを対象への投与の前に少なくとも3継代にわたって培養するステップと、
から成る。
(a)吸引脂肪組織を凍結するステップと、
(b)吸引脂肪組織を解凍し、組織分散酵素を用いて、又は機械的破砕により分散させるステップと、
(c)hADSCを含む細胞分画を遠心分離によってペレッティングし、任意にペレットを、細胞生存率を支持可能な懸濁培地で洗浄し、懸濁液を少なくとも1回の追加の遠心分離にかけるステップと、
(d)ステップ(c)で得られたペレットを、細胞生存率を支持可能な懸濁培地で再懸濁し、少なくとも1回濾過をおこなうステップと、
(e)細胞培養容器への付着性によってhADSCを選択するステップと、
(f)任意に、対象への投与の前にhADSCを少なくとも3継代にわたって培養するステップと、
から成る。
・生細胞数/ml
・死細胞数/ml
・サンプルごとの生細胞の総数
・生存率
・平均細胞サイズ(μm)
・生細胞数/ml
・死細胞数/ml
・サンプルごとの生細胞の総数
・生存率
・平均細胞サイズ(μm)
・MSC形態
・免疫表現型(FACS分析:CD90、CD73、CD45及びCD31)
・回収までの時間(日)
Claims (31)
- 非遺伝子組み換えのヒト脂肪組織由来幹細胞(hADSC)を、それを必要とする対象の中枢神経系(CNS)に投与することを含む、一次進行型多発性硬化症を治療する方法。
- 前記hADSCは、
(a)吸引脂肪組織を凍結するステップと、
(b)前記吸引脂肪組織を解凍し、組織分散酵素を用いて、又は機械的破砕により分散させるステップと、
(c)前記hADSCを含む細胞分画を遠心分離によってペレッティングし、任意に細胞生存率を支持可能な懸濁培地で前記ペレットを洗浄し、前記懸濁液を少なくとも1回の追加の遠心分離にかけるステップと、
(d)ステップ(c)で得られた前記ペレットを、細胞生存率を支持可能な懸濁培地で再懸濁し、再懸濁された前記ペレット内の細胞集団からhADSCを選択するステップと、
(e)任意に、前記hADSCの選択の前に少なくとも1回濾過をおこなうステップと、
(f)任意に、前記hADSCを少なくとも3継代にわたって培養するステップと、
によってヒト皮下脂肪から得られたhADSCである、
請求項1に記載の方法。 - 前記hADSCは、(i)吸引脂肪組織を凍結するステップと、(ii)前記吸引脂肪組織を解凍し、組織分散酵素を用いて、又は機械的破砕により分散させるステップと、(iii)前記hADSCを含む細胞分画を遠心分離によってペレッティングするステップと、(iv)前記ペレットを等張緩衝液又は培養液で洗浄し、追加の遠心分離にかけるステップと、(v)ステップ(iv)で得られた前記ペレットを等張緩衝液又は培養液で再懸濁し、少なくとも1回濾過をおこなうステップと、(vi)再懸濁された前記ペレット内の細胞集団からhADSCを選択するステップと、(vii)前記hADSCを少なくとも3継代にわたって培養するステップと、によってヒト皮下脂肪から得られたhADSCである、
請求項2に記載の方法。 - 遠心分離後に得られた前記hADSCを含む前記細胞分画は、赤血球溶解バッファーにさらされない、請求項2又は請求項3に記載の方法。
- 前記hADSCは、前記細胞培養容器への付着性によって選択される、請求項1〜4のいずれか一項に記載の方法。
- ヒト脂肪組織由来幹細胞(hADSC)を、それを必要とする対象の中枢神経系(CNS)に注入する方法であって、
(a)吸引脂肪組織を凍結するステップと、
(b)前記吸引脂肪組織を解凍し、組織分散酵素を用いて、又は機械的破砕により分散させるステップと、
(c)前記hADSCを含む細胞分画を遠心分離によってペレッティングし、任意に細胞生存率を支持可能な懸濁培地で前記ペレットを洗浄し、前記懸濁液を少なくとも1回の追加の遠心分離にかけるステップと、
(d)ステップ(c)で得られた前記ペレットを、細胞生存率を支持可能な懸濁培地で再懸濁し、少なくとも1回濾過をおこなうステップと、
(e)再懸濁された前記ペレット内の細胞集団からhADSCを選択するステップと、
(f)任意に、前記hADSCを少なくとも3継代にわたって培養するステップと、
(g)前記対象の前記CNSに前記hADSCを注入するステップと、
によってヒト皮下脂肪からhADSCを取得することを含む、方法。 - ヒト皮下脂肪からヒト脂肪組織由来幹細胞(hADSC)を、それを必要とする対象への投与のために取得する方法であって、
(a)吸引脂肪組織を凍結するステップと、
(b)前記吸引脂肪組織を解凍し、組織分散酵素を用いて、又は機械的破砕により分散させるステップと、
(c)前記hADSCを含む細胞分画を遠心分離によってペレッティングし、任意に前記ペレットを、細胞生存率を支持可能な懸濁培地で洗浄し、前記懸濁液を少なくとも1回の追加の遠心分離にかけるステップと、
(d)ステップ(c)で得られた前記ペレットを、細胞生存率を支持可能な懸濁培地で再懸濁し、少なくとも1回濾過をおこなうステップと、
(e)再懸濁された前記ペレット内の細胞集団からhADSCを選択するステップと、
(f)任意に、前記hADSCを前記対象への投与の前に少なくとも3継代にわたって培養するステップと、
を含む、方法。 - 前記hADSCは、組織培養容器への付着性によって選択される、請求項6又は請求項7に記載の方法。
- 前記対象は多発性硬化症(MS)を患っている、請求項6又は請求項7に記載の方法。
- 前記多発性硬化症は進行性MSである、請求項9に記載の方法。
- 前記進行性MSは二次進行型MSである、請求項10に記載の方法。
- 前記進行性MSは一次進行型MSである、請求項10に記載の方法。
- 前記凍結は−80℃で実施され、その後に気相液体窒素が続く、請求項2〜12のいずれか一項に記載の方法。
- 前記組織分散酵素は、コラゲナーゼ、ディスパーゼ又はそれらの組合わせから選択される、請求項2〜13のいずれか一項に記載の方法。
- 前記組織分散酵素はコラゲナーゼである、請求項14に記載の方法。
- 前記hADSCは、前記細胞の少なくとも95%によるCD44、CD73及びCD90の陽性発現と、前記細胞の少なくとも90%によるCD105の陽性発現と、前記細胞の少なくとも95%によるCD45、CD19、CD11b及びHLA−DRの陰性発現とによって特徴付けられる、
請求項1〜15のいずれか一項に記載の方法。 - 前記hADSCは、前記細胞の少なくとも98%によるCD44、CD73及びCD90の陽性発現と、前記細胞の少なくとも90%によるCD105の陽性発現と、前記細胞の少なくとも98%によるCD45、CD19、CD11b及びHLA−DRの陰性発現とによって特徴付けられる、
請求項16に記載の方法。 - 前記hADSCは更に、前記細胞の1〜10%によるCD34の陽性発現によって特徴付けられる、請求項16に記載の方法。
- 前記細胞の少なくとも50%は、CD105、CD73、CD44及びCD90に対して陽性であり、CD45、CD19、CD11b及びHLA−DRに対して陰性である、
請求項16に記載の方法。 - 前記hADSCは、投与の前に継代数3〜10まで培養されたhADSCである、請求項1〜19のいずれか一項に記載の方法。
- 前記hADSCは、投与の前に継代数3〜5まで培養されたhADSCである、請求項20に記載の方法。
- 前記hADSCは1回投与される、請求項1〜21のいずれか一項に記載の方法。
- 前記hADSCは複数回投与される、請求項1〜21のいずれか一項に記載の方法。
- 前記hADSCは2〜8ヶ月毎に1回投与される、請求項23に記載の方法。
- 前記hADSCは3〜12ヶ月毎に1回投与される、請求項23に記載の方法。
- 前記hADSCを投与することは髄腔内投与による、請求項1〜25のいずれか一項に記載の方法。
- 前記hADSCを投与することは室内又は脳室内(ICV)投与による、請求項1〜25のいずれか一項に記載の方法。
- 前記hADSCは自己由来である、請求項1〜27のいずれか一項に記載の方法。
- 前記hADSCは同種由来である、請求項1〜27のいずれか一項に記載の方法。
- 前記hADSCを投与することは、1回の投与につき約105〜3×108個の細胞を投与することを含む、請求項1〜29のいずれか一項に記載の方法。
- 中枢神経系(CNS)への投与による一次進行型多発性硬化症の治療における使用のための、非遺伝子組み換えのヒト脂肪組織由来幹細胞(hADSC)を含む、医薬組成物。
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