JP6890553B2 - 筋ジストロフィーキメラ細胞および筋ジストロフィーの処置方法 - Google Patents
筋ジストロフィーキメラ細胞および筋ジストロフィーの処置方法 Download PDFInfo
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Description
本願は、2015年6月11日出願の米国仮特許出願シリアル番号62/174,122の優先権の利益を主張し、その内容をその全体について参照によって本願明細書に組み入れる。
筋ジストロフィー症(MD)は、動作を制御する骨格筋の進行性の虚弱および変質によって特徴づけられる30を超える遺伝子疾患の群である。MDのいくつかの形態は、幼少または幼年時に見られるが、その他は中年またはそれ以降まで現れない。障害は、筋肉虚弱(MDのいくつかの形態は、心筋に影響する)の分布および程度、発病年齢、進行速度、ならびに遺伝のパターンの見地から異なる。
患者における筋ジストロフィーを処置するためのMDCC組成物および方法が、今や開発された。MDCCラインは、筋芽細胞、間葉系幹細胞または間質細胞の第2集団と共に筋芽細胞の第1集団(自己または同種)の生体外融合によって作られる。MDCCの投与は、患者に筋原性および間葉系原細胞の同時送達を可能にする。したがって、本発明は、筋ジストロフィーを罹患した対象に由来する筋芽細胞および健康なドナーに由来する筋芽細胞;筋ジストロフィーを罹患した対象に由来する筋芽細胞および間葉系幹細胞;健康なドナーに由来する筋芽細胞および間葉系幹細胞;筋ジストロフィーを罹患した対象に由来する筋芽細胞および間質細胞;または健康なドナーに由来する筋芽細胞および間質細胞の融合によって調製されるMDCCを提供する。特定の態様において、本発明のMDCCは、筋ジストロフィーを処置するための方法における使用を見出す。
a)筋ジストロフィーを罹患している対象由来のヒト筋芽細胞および健康なドナー由来のヒト筋芽細胞;
b)筋ジストロフィーに罹患している対象由来のヒト筋芽細胞および健康なドナー由来のヒト間葉系幹細胞;
c)健康なドナー由来のヒト筋芽細胞および健康なドナー由来のヒト間葉系幹細胞;
d)筋ジストロフィーに罹患している対象由来のヒト筋芽細胞、および健康なドナー由来のヒト間質細胞;または
e)健康なドナー由来のヒト筋芽細胞、および健康なドナー由来のヒト間質細胞。
ポリエチレングリコール技術(図1)を用いて、2つの無関係なドナー由来の同種のヒト筋芽細胞およびMSCまたは筋芽細胞の生体外融合を行った。簡潔には、市販(Lonza, Inc.)のヒト筋芽細胞およびMSCを別々に6〜10日間培養した。次に、図1に示すように、PKH−26(赤色)またはPKH−67(緑色)追跡用色素のいずれかを用いて、細胞を蛍光標識した。PEGを用いて融合を行った。二重(PKH26およびPKH67)染色を表す細胞を、蛍光活性化細胞ソーティング(FACS; BD ASTERIOS)によって選択した。融合を確認するために、二重(PKH26およびPKH67)標識MDCCを、共焦点顕微鏡法およびフローサイトメトリーを用いて評価した(図2)。透過型電子顕微鏡を用いてMDCCの形態を評価した。MDCCは、2つの核、融合細胞膜および融合細胞質の存在によって確認された。
健康なsnjおよびmdx(ジストロフィン欠損)の一次筋芽細胞培養およびmdx MSC培養を確立し、生体内で増殖させた。3つのマウス筋芽細胞/MSCおよび筋芽細胞/筋芽細胞融合をポリエチレン−グリコール技術を用いて行った。筋原性分化能と同様に、ジストロフィン発現も融合前後で確認された。
Claims (10)
- 筋ジストロフィーを罹患した対象に由来する筋芽細胞および健康なドナーに由来する筋芽細胞間の融合を含むキメラ細胞であって、生体外融合産物である、前記キメラ細胞。
- 筋ジストロフィーを罹患した対象に由来する筋芽細胞および健康なドナーに由来する筋芽細胞が、異なるドナーに由来する、請求項1に記載のキメラ細胞。
- 筋ジストロフィーを罹患した対象に由来する筋芽細胞または健康なドナーに由来する筋芽細胞が、自己のものまたは同種である、請求項1に記載のキメラ細胞。
- 健康なドナーが対象の父である、請求項1に記載のキメラ細胞。
- 筋ジストロフィーを罹患した対象に由来するヒト筋芽細胞および健康なドナーに由来するヒト筋芽細胞間の融合を含む、請求項1に記載のキメラ細胞。
- 請求項1に記載のキメラ細胞および薬学的に許容し得る担体を含む組成物。
- 処置を必要とする対象に請求項1に記載のキメラ細胞の有効量を投与し、それによって対象の筋ジストロフィーを処置することを含む、筋ジストロフィーを処置する方法における使用のための、請求項6に記載の組成物。
- 筋ジストロフィーがデュシェンヌ型筋ジストロフィーである、請求項7に記載の組成物。
- 前記キメラ細胞が、静脈内注射、骨内注射、または筋肉内注射によって投与される、請求項7に記載の組成物。
- 請求項6〜9のいずれか一項に記載の組成物を含む、筋ジストロフィーを処置するためのキット。
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Application Number | Priority Date | Filing Date | Title |
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US201562174122P | 2015-06-11 | 2015-06-11 | |
US62/174,122 | 2015-06-11 | ||
PCT/US2016/036821 WO2016201182A1 (en) | 2015-06-11 | 2016-06-10 | Muscular dystrophy chimeric cells and method for treating muscular dystrophies |
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JP2018516974A JP2018516974A (ja) | 2018-06-28 |
JP6890553B2 true JP6890553B2 (ja) | 2021-06-18 |
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US (2) | US11147840B2 (ja) |
EP (1) | EP3307065B1 (ja) |
JP (1) | JP6890553B2 (ja) |
CN (1) | CN107920503A (ja) |
AU (1) | AU2016274797B2 (ja) |
CA (1) | CA2988137C (ja) |
ES (1) | ES2962633T3 (ja) |
PL (1) | PL3307065T3 (ja) |
WO (1) | WO2016201182A1 (ja) |
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EP3717635A1 (en) * | 2017-11-28 | 2020-10-07 | The Board of Trustees of the University of Illinois | Multi-chimeric cell and therapy for transplantation and treatment of immune deficiencies and genetic disorders |
WO2020186197A1 (en) * | 2019-03-14 | 2020-09-17 | Dystrogen Therapeutics Corporation | Myoblast chimeric cells (mccs) |
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US4659663A (en) * | 1984-10-01 | 1987-04-21 | Board Of Regents, University Of Texas System | Methods for isolating cell fusion products |
US5538722A (en) | 1989-06-13 | 1996-07-23 | Stanford University | Isolation, growth, differentiation and genetic engineering of human muscle cells |
GB9419048D0 (en) | 1994-09-20 | 1994-11-09 | Watt Diana J | Treatment of muscular disorders |
WO1996018303A1 (en) * | 1994-12-13 | 1996-06-20 | Law Peter K | Myoblast therapy for mammalian diseases |
US20020164313A1 (en) * | 1995-03-16 | 2002-11-07 | Tremblay Jacques P. | Compositions comprising preconditioned myoblasts having enhanced fusion properties |
AU1224200A (en) * | 1998-10-23 | 2000-05-15 | Agnes Vignery | Methods for modulating cell fusion |
WO2002006318A2 (en) * | 2000-07-18 | 2002-01-24 | Board Of Regents, The University Of Texas System | Methods and compositions for stabilizing microtubules and intermediate filaments in striated muscle cells |
JP2004536139A (ja) | 2001-07-23 | 2004-12-02 | バイアセル インコーポレーティッド | 臍帯血細胞を用いた筋ジストロフィーの治療方法 |
US20040001857A1 (en) * | 2002-06-28 | 2004-01-01 | Cheung Ling Yuk | Dietary supplements for treating hypertension |
ATE507290T1 (de) * | 2004-07-27 | 2011-05-15 | Kowa Co | Zellfusionspromotor und dessen nutzung |
CA2538208A1 (en) * | 2005-05-04 | 2006-11-04 | Universite Laval | Modulation of myostatin and use thereof in cell transplantation-based treatment of muscle disease |
US20080286249A1 (en) | 2006-01-12 | 2008-11-20 | Varney Timothy R | Use of mesenchymal stem cells for treating genetic diseases and disorders |
US20070253931A1 (en) * | 2006-01-12 | 2007-11-01 | Osiris Therapeutics, Inc. | Use of mesenchymal stem cells for treating genetic diseases and disorders |
JP2010525794A (ja) * | 2007-04-06 | 2010-07-29 | インターナショナル ステム セル コーポレイション | ヒト単為生殖性胚盤胞に由来する患者特異的幹細胞株 |
US8703180B1 (en) * | 2007-10-23 | 2014-04-22 | Abbott Cardiovascular Systems Inc. | Multiple growth factor compositions, methods of fabrication, and methods of treatment |
WO2010031190A1 (en) * | 2008-09-22 | 2010-03-25 | UNIVERSITé LAVAL | Culture medium for myoblasts, precursors thereof and derivatives thereof |
US10272137B2 (en) | 2013-06-27 | 2019-04-30 | The Board Of Regents Of The University Of Texas System | Compositions and methods relating to myomaker-induced muscle cell fusion |
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PL3307065T3 (pl) | 2024-02-19 |
AU2016274797A1 (en) | 2018-01-18 |
US20220025335A1 (en) | 2022-01-27 |
EP3307065A4 (en) | 2018-04-25 |
WO2016201182A8 (en) | 2017-01-05 |
ES2962633T3 (es) | 2024-03-20 |
US11147840B2 (en) | 2021-10-19 |
CN107920503A (zh) | 2018-04-17 |
AU2016274797B2 (en) | 2018-09-27 |
JP2018516974A (ja) | 2018-06-28 |
EP3307065B1 (en) | 2023-08-02 |
EP3307065A1 (en) | 2018-04-18 |
CA2988137C (en) | 2021-01-26 |
CA2988137A1 (en) | 2016-12-15 |
US20180221416A1 (en) | 2018-08-09 |
WO2016201182A1 (en) | 2016-12-15 |
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