JP2017171675A - 骨芽細胞機能を増加させる方法 - Google Patents
骨芽細胞機能を増加させる方法 Download PDFInfo
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Abstract
【解決手段】本開示は、対象に、幹細胞の集団および/またはその子孫および/またはそれに由来する可溶性因子を全身投与することを含む、対象における骨芽細胞機能を増加させる方法を提供する。
【選択図】なし
Description
本開示は、2011年9月9日に出願された発明の名称「骨芽細胞機能を増加させる方法」の米国特許出願第61/532,772号、および2011年9月16日に出願された発明の名称「骨芽細胞機能を増加させる方法2」の米国特許出願第61/535,441号からの優先権を主張する。
非特許文献2:Posner et al.((1980)J.Biol.Chem.255:8685−91)
非特許文献3:Brozovic et al.(1976)Brit.J Haematol.32:9
本明細書を通じて、具体的にそうでないことが述べられているのでなければ、または文脈がそうでないことを要求しているのでなければ、単一の工程、組成物、工程の群または組成物の群への言及は、1および複数の(すなわち、1以上の)それらの工程、組成物、工程の群または組成物の群を含むと把握されるべきである。
本明細書中で用いるように、用語「幹細胞」とは、表現型的におよび遺伝子型的に同一な娘ならびに少なくとも1つの他の最終細胞型(例えば、最後に分化した細胞)を生起させることができる自己−再生性細胞をいう。用語「幹細胞」は、分化全能性、分化多能性および多能性細胞、ならびにその分化から由来する先祖細胞および/または前駆細胞を含む。幹細胞は成体または胚性幹細胞であってよく、または誘導多能性幹(iPS)であってよい。
1つの例において、幹細胞および/またはその子孫細胞を遺伝子改変して、例えば、注目するタンパク質を発現させ、および/または分泌させる。例えば、細胞を操作して、代謝性骨障害または男性不妊の治療で有用なタンパク質を発現させる。
低い骨芽細胞のレベルまたは活性に関連する障害の開始または進行を治療し、または予防し、または遅延させる細胞または可溶性因子の能力を決定するための方法は当業者に明らかであろう。
(i)低い骨芽細胞のレベルまたは活性に関連する障害を患っている被験者に細胞または可溶性因子を投与し、該被験者において該障害の兆候を評価し;
(ii)(i)における被験者の低い骨芽細胞のレベルまたは活性に関連する障害の兆候を、細胞または可溶性因子が投与されていない該障害を患っている対照被験者の低い骨芽細胞のレベルまたは活性に関連する障害の兆候と比較する;
ことを含み、
ここに、対照被験者と比較した被験者における兆候の改善は、該細胞または可溶性因子が該障害を治療することを示す。
本開示の1つの例において、幹細胞および/またはその子孫細胞は組成物の形態で投与される。1つの例において、そのような組成物は医薬上許容される担体および/または賦形剤を含む。
本開示の1つの例において、幹細胞−由来および/または子孫細胞−由来の上清または可溶性因子は、例えば、適当な担体および/または賦形剤を含む組成物の形態で投与される。1つの例において、担体または賦形剤は可溶性因子または上清の生物学的効果に悪影響しない。
幹細胞−由来の上清または可溶性因子、幹細胞またはその子孫は、他の有益な薬物または生物学的分子(成長因子、栄養因子)と共に投与してよい。他の剤と共に投与する場合、それらは単一の医薬組成物中にて、または別々の医薬組成物中にて、同時に、または他の剤と共に順次に(他の剤の投与の前または後いずれかに)一緒に投与してよい。共投与することができる生物活性因子としては、抗−アポトーシス剤(例えば、EPO、EPOミメティボディ、TPO、IGF−IおよびIGF−II、HGF、カスパーゼ阻害剤);抗−炎症剤(例えば、p38MAPK阻害剤、TGF−ベータ阻害剤、スタチン、IL−6およびIL−1阻害剤、ペミロラスト(PEMIROLAST)、トラニラスト(TRANILAST)、レミケード(REMICADE)、シロリムス(SIROLIMUS)、およびNSAID(非−ステロイド抗−炎症薬物;例えば、テポキサリン(TEPOXALIN)、トルメチン(TOLMETIN)、スプロフェン(SUPROFEN));免疫抑制/免疫調節剤(例えば、サイクロスポリン、タクロリムスのようなカルシニューリン阻害剤);mTOR阻害剤(例えば、シロリムス(SIROLIMUS)、エボロリムス(EVEROLIMUS));抗−増殖剤(例えば、アザチオプリン、ミコフェノール酸モフェチル);コルチコステロイド(例えば、プレドニゾロン、ヒドロコルチゾン);モノクローナル抗−IL−2Rアルファ受容体抗体(例えば、バシリキシマブ、ダクリズマブ)、ポリクローナル抗−T−細胞抗体(例えば、抗−胸腺細胞グロブリン(ATG)のような抗体;抗−リンパ球グロブリン(ALG);モノクローナル抗−T細胞抗体(OKT3);抗−血栓形成性剤(例えば、ヘパリン、ヘパリン誘導体、ウロキナーゼ、PPack(デキストロフェニルアラニンプロリンアルギニンクロロメチルケトン)、抗−トロンビン化合物、血小板受容体アンタゴニスト、抗−トロンビン抗体、抗−血小板受容体抗体、アスピリン、ジピリダモール、プロタミン、ヒルジン、プロスタグランジン阻害剤、および血小板阻害剤);および抗−オキシダント(例えば、プロブコール、ビタミンA、アスコルビン酸、トコフェロール、補酵素Q−10、グルタチオン、L−システイン、N−アセチルシステイン)ならびに局所麻酔剤が挙げられる。
本開示は、いずれかの例による本明細書中で記載された方法で用いるための、または該方法で用いる場合の医療機器も提供する。例えば、本開示は、いずれかの例による本明細書中に記載された幹細胞および/またはその子孫細胞および/またはそれからの可溶性因子および/または組成物を含むシリンジまたはカテーテルまたは他の適当な送達デバイスを提供する。所望により、シリンジまたはカテーテルは、いずれかの例による本明細書中に記載された方法で用いるための説明書で包装してよい。
1つの例において、幹細胞―由来の上清または可溶性因子、幹細胞またはその子孫は対象の血流に送達される。例えば、幹細胞―由来の上清または可溶性因子、幹細胞またはその子孫は非経口送達される。非経口投与の例示的な経路としては、限定されるものではないが、腹腔内、心室内、脳室内、髄腔内または静脈内が挙げられる。1つの例において、幹細胞―由来の上清または可溶性因子、幹細胞またはその子孫は動脈内、大動脈、心臓の心房または心室に、または血管に、例えば、静脈内送達される。
骨髄(BM)は健康な通常の成人ボランティア(20〜35歳)から収穫する。簡単に述べれば、40mlのBMを後部腸骨稜からリチウム―ヘパリン抗凝固剤―含有試験管に吸引する。
実験を設計して、細胞STRO−1ブライト細胞を単離するための単一の試薬としてSTRO−3 mAbの使用の潜在能力を確認した。
サル骨髄先祖細胞(カニクイザルからのもの;cyno−MPC)を、雌Macaca fascicularisから収集した〜15mlの骨髄吸引物から単離した。骨髄吸引物懸濁液を、Ficollグラジエントを用いて分離し、および洗浄して、無核細胞(赤血球細胞)を除去した。次いで、CA12抗体(抗−STRO−3)およびDynalbeadsを攻撃することによって、有核細胞をカウントした。抗体およびビーズを付着させた細胞を、MPC−1磁石の磁場によって陽性選択した。陽性の選択された細胞をカウントし、成長培地中において継代(p.)0にてT−フラスコに撒いた。予備的選択、陽性および陰性細胞をコロニー形成検定(CFU−F)で用いた。
5匹のカニクイザルを、以下の基準:(i)年齢>14年、(ii)高絶食血中グルコース(>105mg/dL)、絶食血中インスリンレベル(<60mU/L)、(iii)高BMI(>46雄 >24雌)、(iv)雄については8kgを超える体重および雌については>3.5kg体重、(v)高絶食トリグリセリド;および(vi)IVGTTに基づいた鈍い相1インスリン応答に基づいて治療のために選択した。
オステオカルシンのサンプリングは週:−4、−2、0、2、4、8、12、20、24に行った。
アルカリホスファターゼのサンプリングは週:−2、2、4、6、8、12、14、16、18、20、22、24に行った。
血中オステオカルシン(ng/ml)についての絶食プロファイルを、個々の動物に対する同種異系MPCのIV注射に続いて6カ月間モニターした。結果を図3に示し、そこでは、矢印はMPCの単一の用量の投与の時間を示す。
Claims (30)
- 対象に、幹細胞の集団および/またはその子孫および/またはそれに由来する可溶性因子を全身投与することを含む、対象における骨芽細胞機能を増加させる方法。
- 該幹細胞が多能性細胞である請求項1に記載の方法。
- 該多能性細胞がSTRO−1+細胞である請求項2に記載の方法。
- 該多能性細胞がSTRO−1ブライト細胞である請求項2に記載の方法。
- 該幹細胞が対象における骨芽細胞によりオステオカルシンの生産を刺激する請求項1〜4のいずれか一項に記載の方法。
- 該対象が低い骨芽細胞のレベルまたは活性に関連する障害を患っている請求項1〜5のいずれか一項に記載の方法。
- 該障害が代謝性骨障害または男性不妊である請求項6に記載の方法。
- 該代謝性骨障害が、骨軟化症、骨粗鬆症、骨化石病、パジェット病およびX染色体性低リン酸塩血症性くる病、腎不全−関連骨形成異常症、大理石骨病、嚢胞性線維性骨炎およびグルココルチコイド−誘導骨喪失よりなる群から選択される請求項7に記載の方法。
- 該対象が骨粗鬆症を患っており、該方法が骨折の危険性を予防しまたは低下させる請求項6に記載の方法。
- 該対象が骨折を患っている請求項1〜8のいずれか一項に記載の方法。
- 該方法が骨折の治癒を加速し、および/または遷延治癒骨折を予防し、および/または骨折の癒着不能を予防する請求項10に記載の方法。
- 幹細胞の集団および/またはその子孫および/またはそれに由来する可溶性因子の投与の結果、対象における血漿中オステオカルシンレベルの増大がもたらされる請求項1〜11のいずれか一項に記載の方法。
- 幹細胞の集団および/またはその子孫および/またはそれに由来する可溶性因子の投与の結果、2週間の投与内で血漿中オステオカルシンレベルの少なくとも5倍の増加がもたらされる請求項12に記載の方法。
- 幹細胞の集団および/またはその子孫および/またはそれに由来する可溶性因子の投与の結果、2週間の投与内で血漿中オステオカルシンレベルの少なくとも10倍の増加がもたらされる請求項12に記載の方法。
- 幹細胞の集団および/またはその子孫および/またはそれに由来する可溶性因子の投与の結果、2週間の投与内で血漿中オステオカルシンレベルの少なくとも20倍の増加がもたらされる請求項12に記載の方法。
- 幹細胞の集団および/またはその子孫および/またはそれに由来する可溶性因子の投与の結果、対象における血漿中アルカリホスファターゼレベルの増加がもたらされる請求項1〜15のいずれか一項に記載の方法。
- 幹細胞の集団および/またはその子孫および/またはそれに由来する可溶性因子の投与の結果、投与前の血漿中アルカリホスファターゼのレベルと比較して、6週間の投与内で血漿中アルカリホスファターゼレベルの少なくとも5パーセント増加がもたらされる請求項16に記載の方法。
- 幹細胞の集団および/またはその子孫および/またはそれに由来する可溶性因子の投与の結果、投与前の血漿中アルカリホスファターゼのレベルと比較して、6週間の投与内で血漿中アルカリホスファターゼレベルの少なくとも10パーセント増加がもたらされる請求項16に記載の方法。
- 幹細胞の該集団および/または該子孫および/または該可溶性因子が対象に複数回投与される請求項1〜18のいずれか一項に記載の方法。
- 該集団および/または該子孫および/または該可溶性因子が12週間毎に1回、またはそれよりも長い週間毎に1回投与される請求項19に記載の方法。
- kg当たり、0.1×106〜5×106の間のSTRO−1+多能性細胞および/またはその子孫を投与することを含む請求項1〜20のいずれか一項に記載の方法。
- kg当たり、0.3×106〜2×106の間の多能性STRO−1+細胞および/またはその子孫を投与することを含む請求項1〜21のいずれか一項に記載の方法。
- 低い用量の多能性STRO−1+細胞および/またはその子孫を投与することを含む請求項1〜22のいずれか一項に記載の方法。
- 該低い用量のSTRO−1+細胞および/またはその子孫が、kg当たり、0.1×105および0.5×106の間のSTRO−1+細胞および/またはその子孫を含む請求項23に記載の方法。
- 該低い用量のSTRO−1+細胞および/またはその子孫が、kg当たり、約0.3×106のSTRO−1+細胞および/またはその子孫を含む請求項23に記載の方法。
- 幹細胞の該集団および/または子孫細胞が自己または同種異系であり、および/または該可溶性因子が自己または同種異系細胞に由来し得る請求項1〜25のいずれか一項に記載の方法。
- 多能性細胞の該集団および/または子孫細胞が、投与前および/または該可溶性因子を得る前に培養拡大されたものである請求項1〜26のいずれか一項に記載の方法。
- 多能性細胞の該集団が、STRO−1ブライトである、および/または組織非特異的アルカリホスファターゼ(TNAP)を発現する、および/または該子孫細胞および/または該可溶性因子が、STRO−1ブライトである、および/またはTNAPを発現するSTRO−1+細胞に由来する、請求項1〜27のいずれか一項に記載の方法。
- 該幹細胞および/またはその子孫および/またはそれに由来する可溶性因子が静脈内投与される請求項1〜29のいずれか一項に記載の方法。
- 該幹細胞および/またはその子孫細胞および/またはそれに由来する可溶性因子が、該幹細胞および/またはその子孫細胞および/またはそれに由来する可溶性因子および担体および/または賦形剤を含む組成物の形態で投与される請求項1〜29のいずれか一項に記載の方法。
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CA2971512A1 (en) * | 2014-12-23 | 2016-06-30 | Mesoblast International Sarl | Method for treating heart failure |
CN110613736A (zh) * | 2019-10-30 | 2019-12-27 | 广州陈运贤生命科技有限公司 | 一种用于治疗骨髓衰竭疾病的组合物、制剂及制备方法和应用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006134921A1 (ja) * | 2005-06-13 | 2006-12-21 | National University Corporation Nagoya University | 移植材料及び骨質改善剤 |
JP2008520185A (ja) * | 2004-09-24 | 2008-06-19 | アンジオブラスト システムズ,インコーポレーテッド | 分化多能性増殖間葉系前駆細胞子孫(memp)およびその使用 |
JP2008538495A (ja) * | 2005-04-12 | 2008-10-30 | アンジオブラスト・システムズ・インコーポレーテッド | 組織非特異的アルカリホスファターゼによる成体多能性細胞の単離 |
JP6363950B2 (ja) * | 2011-09-09 | 2018-07-25 | メゾブラスト・インコーポレイテッドMesoblast, Inc. | 骨芽細胞機能を増加させる方法 |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5139941A (en) | 1985-10-31 | 1992-08-18 | University Of Florida Research Foundation, Inc. | AAV transduction vectors |
AU8200191A (en) | 1990-07-09 | 1992-02-04 | United States of America, as represented by the Secretary, U.S. Department of Commerce, The | High efficiency packaging of mutant adeno-associated virus using amber suppressions |
US5173414A (en) | 1990-10-30 | 1992-12-22 | Applied Immune Sciences, Inc. | Production of recombinant adeno-associated virus vectors |
US5837539A (en) | 1990-11-16 | 1998-11-17 | Osiris Therapeutics, Inc. | Monoclonal antibodies for human mesenchymal stem cells |
US5226914A (en) | 1990-11-16 | 1993-07-13 | Caplan Arnold I | Method for treating connective tissue disorders |
JP3534749B2 (ja) | 1991-08-20 | 2004-06-07 | アメリカ合衆国 | アデノウイルスが介在する胃腸管への遺伝子の輸送 |
AUPQ147799A0 (en) | 1999-07-07 | 1999-07-29 | Medvet Science Pty. Ltd. | Mesenchymal precursor cell |
AU2003901668A0 (en) | 2003-03-28 | 2003-05-01 | Medvet Science Pty. Ltd. | Non-haemopoietic precursor cells |
DE19939781C2 (de) | 1999-08-21 | 2003-06-18 | Schott Glas | Skulltiegel für das Erschmelzen oder das Läutern von anorganischen Substanzen, insbesondere von Gläsern und Glaskeramiken |
WO2006029347A2 (en) | 2004-09-03 | 2006-03-16 | University Of Maryland, Baltimore | Integrin cd18 is a novel stromal stem cell marker and functions to promote osteogenesis |
EP2361970A1 (en) | 2004-09-24 | 2011-08-31 | Angioblast Systems Incorporated | Method of enhancing proliferation and/or survival of mesenchymal precursor cells (MPC) |
GB0600972D0 (en) * | 2006-01-18 | 2006-03-01 | Univ Leeds | Enrichment of cells |
WO2008003042A2 (en) * | 2006-06-28 | 2008-01-03 | The University Of Medicine And Dentistry Of New Jersey | Amnion-derived stem cells and uses thereof |
WO2009015343A2 (en) * | 2007-07-25 | 2009-01-29 | Bioe, Inc. | Differentiation of multi-lineage progenitor cells to chondrocytes |
WO2009018613A1 (en) * | 2007-08-06 | 2009-02-12 | Angioblast Systems, Inc. | Methods of generating, repairing and/or maintaining connective tissue in vivo |
US7639486B2 (en) * | 2007-12-13 | 2009-12-29 | International Business Machines Corporation | Rack system providing flexible configuration of computer systems with front access |
DK2297304T3 (da) * | 2008-05-07 | 2017-11-06 | Bone Therapeutics Sa | Humane knogledannende celler til behandling af tilstande og knoglesygdomme forbundet med immunodefekt eller immunsuppression |
CN105030828B (zh) | 2008-06-25 | 2020-10-02 | 麦瑟布莱斯特公司 | 椎间盘的修复和/或重建 |
US8722398B2 (en) | 2009-12-22 | 2014-05-13 | Agency For Science, Technology And Research | Treatment of bone fracture |
CA2788579A1 (en) | 2010-02-02 | 2011-08-11 | Matthew J. Hilton | Methods of isolating and culturing mesenchymal stem cells |
US9405700B2 (en) | 2010-11-04 | 2016-08-02 | Sonics, Inc. | Methods and apparatus for virtualization in an integrated circuit |
-
2012
- 2012-09-07 CN CN201280043642.9A patent/CN103857401B/zh active Active
- 2012-09-07 EP EP12829951.8A patent/EP2753342B1/en active Active
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- 2017-04-12 US US15/485,637 patent/US20170274016A1/en not_active Abandoned
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-
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- 2019-01-24 HK HK19101230.7A patent/HK1259180A1/zh unknown
- 2019-07-02 US US16/460,734 patent/US11135249B2/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008520185A (ja) * | 2004-09-24 | 2008-06-19 | アンジオブラスト システムズ,インコーポレーテッド | 分化多能性増殖間葉系前駆細胞子孫(memp)およびその使用 |
JP2008538495A (ja) * | 2005-04-12 | 2008-10-30 | アンジオブラスト・システムズ・インコーポレーテッド | 組織非特異的アルカリホスファターゼによる成体多能性細胞の単離 |
WO2006134921A1 (ja) * | 2005-06-13 | 2006-12-21 | National University Corporation Nagoya University | 移植材料及び骨質改善剤 |
JP6363950B2 (ja) * | 2011-09-09 | 2018-07-25 | メゾブラスト・インコーポレイテッドMesoblast, Inc. | 骨芽細胞機能を増加させる方法 |
Non-Patent Citations (1)
Title |
---|
BIOMATERIALS, vol. 28, JPN6016017655, 2007, pages 249 - 255, ISSN: 0003744284 * |
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US11135249B2 (en) | 2021-10-05 |
CN108635377A (zh) | 2018-10-12 |
US20170274016A1 (en) | 2017-09-28 |
CN103857401A (zh) | 2014-06-11 |
TR201809635T4 (tr) | 2018-07-23 |
US20140363404A1 (en) | 2014-12-11 |
WO2013033777A1 (en) | 2013-03-14 |
JP6444448B2 (ja) | 2018-12-26 |
US9642878B2 (en) | 2017-05-09 |
IL231327A0 (en) | 2014-04-30 |
AU2016219601A1 (en) | 2016-09-08 |
EP2753342A1 (en) | 2014-07-16 |
HK1197183A1 (en) | 2015-01-09 |
JP2014525466A (ja) | 2014-09-29 |
EP2753342B1 (en) | 2018-04-11 |
EP2753342A4 (en) | 2015-03-11 |
CN103857401B (zh) | 2018-06-05 |
CN108635377B (zh) | 2022-06-24 |
ES2676886T3 (es) | 2018-07-25 |
SG11201400218YA (en) | 2014-03-28 |
AU2012307086B2 (en) | 2016-05-26 |
KR20140082660A (ko) | 2014-07-02 |
AU2012307086A1 (en) | 2013-05-02 |
CA2847575A1 (en) | 2013-03-14 |
JP6363950B2 (ja) | 2018-07-25 |
US20190343887A1 (en) | 2019-11-14 |
CA2847575C (en) | 2021-10-19 |
KR102009056B1 (ko) | 2019-08-08 |
EP3351256A1 (en) | 2018-07-25 |
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