JP2015510391A - 脱細胞されて再構築された胎盤の脈管足場を含むオルガノイド - Google Patents
脱細胞されて再構築された胎盤の脈管足場を含むオルガノイド Download PDFInfo
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Abstract
Description
本出願は、脱細胞化胎盤の脈管足場(scaffold)を含む、又は、脱細胞化胎盤の脈管足場からなる、オルガノイド、並びにその製造及び使用方法を提供する。
生理機能的に、病気となるか、損傷するか、又は外科的に切除された組織の代替に対する、大きな医学的要求がある。そこで本出願は、脱細胞化胎盤の脈管足場を含むオルガノイド、及びその製造使用方法を提供し、その要求に答えることとする。
本発明は、1以上の型の細胞を含み、かつ、脱細胞化胎盤の脈管足場を含む、オルガノイドを提供するものであり、前記オルガノイドは、臓器又は臓器由来組織の少なくとも1の機能を達成し、前記臓器又は臓器由来組織の少なくとも1の機能は、該臓器又は組織由来の少なくとも1の細胞型に特徴的な、タンパク質、成長増殖因子、サイトカイン、インターロイキン、又は小分子を産生することであり、前記脱細胞化胎盤の脈管(vascular)足場は、実質的に損傷がない胎盤の脈管構造マトリックスを含む、オルガノイドを提供するが、その場合、胎盤からマトリックスが得られ、胎盤の脈管構造は、脱細胞処理及びその次に続くオルガノイドの製造中で実質的に保存される。
更に別の特別な態様において、前記オルガノイドは更に甲状腺上皮細胞及び傍濾胞細胞を含む。
内皮細胞、上皮細胞、真皮細胞、内胚葉細胞、中胚葉細胞、線維芽細胞、骨細胞、軟骨細胞、ナチュラルキラー細胞、樹状細胞、肝細胞(hepatic cell)、膵臓細胞、又は間質細胞;
唾液腺粘液性細胞、唾液腺漿液性細胞、エブネル腺細胞、乳腺細胞、涙腺細胞、耳道腺細胞、エクリン汗腺暗調細胞、エクリン汗腺明調細胞、アポクリン汗腺細胞、モル腺細胞、脂腺細胞、ボウマン腺細胞、ブルンネル腺細胞、精嚢細胞、前立腺細胞、尿道球腺細胞、バルトリン腺細胞、尿道腺細胞、子宮内膜細胞、単離された杯細胞、胃壁の粘液性細胞、胃腺酵素原細胞、胃腺酸分泌細胞、膵腺房細胞、パネート細胞、II型肺胞上皮細胞、クララ細胞;
成長ホルモン(ソマトトロピン)産生細胞、乳腺刺激ホルモン(プロラクチン)産生細胞、甲状腺刺激ホルモン産生細胞、性腺刺激ホルモン(ゴナドトロピン)産生細胞、副腎皮質刺激ホルモン産生細胞(corticotropes)、下垂体中葉細胞、巨大細胞神経分泌細胞、腸管細胞、気道細胞、甲状腺上皮細胞、傍濾胞細胞、副甲状腺細胞、副甲状腺主細胞、好酸性細胞;
副腎腺細胞、クロム親和性細胞、ライディッヒ細胞、内卵胞膜細胞、黄体細胞、顆粒膜黄体細胞、卵胞膜黄体細胞、傍糸球体細胞、緻密斑細胞、極周囲細胞、メサンギウム細胞、
血管及びリンパ管(lymphatic vascular)内皮有窓型細胞、血管及びリンパ管内皮連続型細胞、血管及びリンパ管内皮脾(splenic)細胞、滑膜細胞、漿膜細胞(腹膜の、胸膜の、及び心膜腔の内壁(lining))、扁平上皮細胞、円柱細胞、暗調細胞、前庭膜細胞(耳の内リンパ腔内壁)、血管条基底細胞、血管条周辺細胞(耳の内リンパ腔内壁)、クラウディウス細胞、ベッチェル細胞、脈絡叢細胞、軟膜クモ膜扁平上皮細胞、色素毛様体上皮細胞、非色素毛様体上皮細胞、角膜内皮細胞、栓細胞(peg cell)、
気道繊毛細胞、卵管繊毛細胞、子宮内膜繊毛細胞、精巣網繊毛細胞、精巣輸出管繊毛細胞、繊毛性上衣細胞、
表皮(epidermal)角化細胞、表皮基底細胞、指爪及び足指爪の角化細胞、爪床基底細胞、毛幹の毛髄質細胞、毛幹の毛皮質細胞、毛幹の毛小皮細胞、毛根の毛小皮鞘細胞、毛根ハックスレー層の鞘細胞、毛根ヘンレ層の鞘細胞、外毛根鞘細胞、毛母細胞、
重層扁平上皮の表面上皮細胞、上皮基底細胞、泌尿器上皮細胞、
耳のコルチ器官の内有毛細胞、耳のコルチ器官の外有毛細胞、嗅上皮基底細胞、冷感受性一次感覚ニューロン、熱感受性一次感覚ニューロン、表皮のメルケル細胞、嗅覚受容体神経、痛み感受性一次感覚ニューロン、光受容体桿体細胞、光受容体青色感受性錐体細胞、光受容体緑色感受性錐体細胞、光受容体赤色感受性錐体細胞、自己(固有)受容性一次感覚ニューロン、触覚感受性一次感覚ニューロン、I型頸動脈小体細胞、II型頸動脈小体細胞(血液pHセンサ)、内耳前庭器官のI型有毛細胞(加速度及び重力)、内耳前庭器官のII型有毛細胞、I型味蕾細胞、
コリン作動性神経細胞、アドレナリン作動性神経細胞、ペプチド作動性神経細胞、
コルチ器官の内柱細胞、コルチ器官の外柱細胞、コルチ器官の内指骨細胞、コルチ器官の外指骨細胞、コルチ器官の境界細胞、コルチ器官のヘンゼン細胞、前庭器支持細胞、味蕾支持細胞、嗅上皮支持細胞、シュワン細胞、サテライト細胞、腸内グリア細胞、
星状細胞、ニューロン、オリゴデンドロサイト、紡錘形ニューロン、
前水晶体上皮細胞、クリスタリン含有水晶体線維細胞、
肝細胞、含脂肪細胞、白色脂肪細胞、褐色脂肪細胞、肝臓脂肪細胞(lipocyte)、
腎臓糸球体壁細胞、腎臓糸球体有足細胞、腎臓近位尿細管刷子縁細胞、ヘンレ係蹄の細い部分の細胞、腎臓遠位尿細管細胞、腎臓集合管細胞、I型肺胞上皮細胞、膵管細胞、非線条(nonstriated)導管細胞、導管細胞、腸刷子縁細胞、外分泌腺線条導管細胞、胆嚢上皮細胞、精巣輸出管非繊毛細胞、精巣上体主細胞、精巣上体基底細胞、
エナメル芽細胞上皮細胞、半月面上皮細胞、コルチ器官歯間上皮細胞、疎性結合組織線維芽細胞、角膜実質細胞(keratocyte)、腱線維芽細胞、骨髄網状組織線維芽細胞、非上皮性線維芽細胞、周細胞、髄核細胞、セメント芽細胞/セメント細胞、造歯細胞、象牙芽細胞、ヒアリン軟骨細胞、線維軟骨細胞、弾性軟骨細胞、骨芽細胞、骨細胞、破骨細胞、骨前駆細胞、硝子体細胞、星細胞(耳)、肝星細胞(伊東細胞)、膵星細胞、
赤色骨格筋細胞、白色骨格筋細胞、中間体骨格筋細胞、筋紡錘の核袋細胞、筋紡錘の核鎖細胞、サテライト細胞、通常の心筋細胞、結節性(nodal)心筋細胞、プルキンエ線維細胞、平滑筋細胞、虹彩の筋上皮細胞、外分泌腺の筋上皮細胞、
網状赤血球、巨核球、単球、結合組織マクロファージ、表皮ランゲルハンス細胞、樹状細胞、ミクログリア細胞、好中球、好酸球、好塩基球、マスト細胞、ヘルパーT細胞、サプレッサーT細胞、細胞傷害性T細胞、ナチュラルキラーT細胞、B細胞、ナチュラルキラー細胞、
メラニン形成細胞、網膜色素上皮細胞、
卵原細胞/卵母細胞、***細胞、***細胞、精原細胞、***、卵胞細胞、セルトリ細胞、胸腺上皮細胞、及び/又は間質性腎臓細胞。
3.1図面の簡単な説明
本発明は、1以上の型の細胞を含み、かつ、脱細胞化胎盤の脈管足場を含む、オルガノイドを提供するものであり、前記オルガノイドは、臓器又は臓器由来組織の少なくとも1の機能を達成し、前記臓器又は臓器由来組織の少なくとも1の機能は、該臓器又は組織由来の少なくとも1の細胞型に特徴的な、タンパク質、成長増殖因子、サイトカイン、インターロイキン、又は小分子を産生することであり、前記脱細胞化胎盤の脈管(vascular)足場は、実質的に損傷がない胎盤の脈管構造マトリックスを含む、オルガノイドを提供するが、その場合、胎盤からマトリックスが得られ、胎盤の脈管構造は、脱細胞処理及びその次に続くオルガノイドの製造中で実質的に保存される。ある態様において、オルガノイドが完成すると、血液又は他の栄養液は前記胎盤の脈管構造を通過する。
一般的に、ヒト胎盤は正常な出産後の娩出後直ぐに回収されるか、又は帝王切開後に回収される。好ましい態様においては、胎盤は、インフォームドコンセント後であって、患者の完全で胎盤に関連する病理記録が得られた後、患者から回収される。好ましくは、病理記録は分娩後も継続される。このような病理記録は、胎盤やそれから採取された幹細胞の次の使用に整合するように使用できる。例えば、ヒト胎盤幹細胞は、病理記録に照らして、胎盤に関連する幼児、又は幼児の両親、兄弟姉妹若しくは他の親戚のための個別化医療に使用できる。
胎盤が、上記のとおり用意され、任意で潅流されると、それは、胎盤の脈管構造の本来の構造を保存するように、例えば胎盤の脈管構造を実質的に損傷なく残すように脱細胞化される。本明細書における「実質的に損傷がない」は、脱細胞処理後に残る胎盤の脈管構造が、脱細胞処理前の胎盤の脈管構造の、全て又はほとんどの全体構造を維持していることを意味する。ある態様において、胎盤の脈管構造は、胎盤の脈管構造を再生するために、例えば脈管内皮細胞又は他の細胞で再播種されることができる。
細胞は、生理学的に許容されるいずれかの方法により、脱細胞化胎盤の脈管足場上に担持できる。ある態様において、細胞は、液体培養培地、塩溶液又は緩衝溶液等の中で懸濁され、細胞含有液体は胎盤の脈管足場内へ1以上の脈管マトリックスを通じで潅流される。胎盤の脈管足場は又、細胞を含有する液体培養培地、塩溶液又は緩衝溶液内で、複数の細胞が前記胎盤の脈管足場へ付着するために充分な時間の間培養されてもよい。細胞は又、足場の表面上への播種によるか、針又は注入ポンプ等を使用して脈管内へ細胞を注入することにより、胎盤の脈管マトリックス上へ担持できる。ある態様において、細胞は、バイオプリンティングにより、脱細胞化胎盤の脈管足場上へ担持される。
生理的機能に応じて、オルガノイドは、増加又は交換するために設計される。本発明のオルガノイドは、1以上の関連する細胞型を含むことができる。
本発明で提供されるオルガノイドの主要な機能は、その中にそれが含まれている細胞により、オルガノイドが、その増加又は交換が必要な個体内の1以上の生理的機能等の、1以上の生理的機能を達成することである。更に具体的には、オルガノイド及び/又はそれが含まれる細胞は、前記オルガノイドのレシピエントである個体内の臓器又は組織の1以上の生理的機能を、複製又は増加させる。ある態様において、前記のとおり、オルガノイドは1以上の生理的機能を達成する単離された主要な又は培養された細胞を含む。他の態様において、オルガノイドは、生理的機能を達成するように遺伝子工学的に設計された細胞を含む。特別な態様において、前記遺伝子工学的に設計された細胞は、対応する非設計細胞により天然に産生されたものではないタンパク質又はポリペプチドを産生するか、又は、対応する非設計細胞により天然に産生されるよりも多くの量でタンパク質又はポリペプチドを産生するように遺伝子工学的に設計されており、前記細胞組成物は分化した細胞を含むものである。
腺特異的オルガノイドの特別な態様が、下記4.6.1〜4.6.6項のそれぞれに提示される。
下垂体は、接合している血管網に囲まれている、下垂体前葉内の細胞、好酸性細胞及びクロム親和性細胞(chromophils)、並びに下垂体後葉内の神経分泌細胞のボディを含む。従って、ある態様において、本発明では、下垂体の少なくとも1の生理的機能を達成するオルガノイドを提供し、例えば、本発明は下垂体の(pituitary)オルガノイドを提供する。特別な態様において、前記下垂体又は前記下垂体のオルガノイドの少なくとも1の生理的機能は、検出可能な量の1以上の、例えば、1以上のヒト成長ホルモン(hGH)、プロラクチン(PRL)、副腎皮質刺激ホルモン(ACTH)(コルチコトロピン)、メラニン形成細胞刺激ホルモン(MSH)、甲状腺刺激ホルモン(TSH)(サイロトロピンthyrotrophin)、卵胞刺激ホルモン(FSH)、黄体形成ホルモン(LH)、抗利尿ホルモン(ADH)、及び/又はオキシトシン等の下垂体特異性ホルモンを産生することである。ある態様において、前記オルガノイドは、検出可能な量の1以上の、例えば、1以上のヒト成長ホルモン(hGH)、プロラクチン(PRL)、副腎皮質刺激ホルモン(ACTH)(コルチコトロピン)、メラニン形成細胞刺激ホルモン(MSH)、甲状腺刺激ホルモン(TSH)(サイロトロピン)、卵胞刺激ホルモン(FSH)、黄体形成ホルモン(LH)、抗利尿ホルモン(ADH)、及び/又はオキシトシン等の下垂体特異性ホルモンを産生するように遺伝子工学的に設計されている細胞を含む(例えば、追加的に含む)。
甲状腺は、コロイドを分泌する甲状腺濾胞細胞、T3及びT4を産生する甲状腺上皮細胞、及びカルシトニンを産生する甲状腺傍濾胞細胞を含む。ある態様において、従って、本発明では、甲状腺の少なくとも1の生理的機能を達成するオルガノイドを提供し、例えば、本発明は甲状腺の(thyroid)オルガノイドを提供する。特別な態様において、前記甲状腺又は前記甲状腺のオルガノイドの少なくとも1の生理的機能は、検出可能な量の1以上の、例えば、1以上のトリヨードチロニン(T3)、チロキシン(T4)及び/又はカルシトニン等の甲状腺特異性ホルモンを産生することである。前記1以上の甲状腺特異性ホルモンの前記オルガノイドによる産生は、例えば、商業的に入手可能なキット及びアッセイにより評価分析できる。例えば、T3産生は、Total T3 ELISA Kit(MyBiosource、San Diego、CA)を使用してイン・ビトロ評価分析でき、T4産生は、Total T4ELISA Kit(MyBiosource、San Diego、CA)を使用してイン・ビトロ評価分析でき、カルシトニン産生は、カルシトニンELISA Kit(MyBiosource、San Diego、CA)を使用してイン・ビトロ評価分析できる。ある態様において、前記オルガノイドは、検出可能な量の1以上の、例えば、1以上のT3、T4及び/又はカルシトニン等の甲状腺特異性ホルモンを産生するように遺伝子工学的に設計されている細胞を含む(例えば、追加的に含む)。上述の評価分析のそれぞれでは、ある態様において、オルガノイドが培養された培養培地が、前記オルガノイドによる特別なホルモンの産生のために評価分析される。
副甲状腺は主に、副甲状腺ホルモンの産生に寄与する副甲状腺主細胞及び副甲状腺好酸性細胞の2種類の細胞を含む。ある態様において、従って、本発明では、副甲状腺の少なくとも1の生理的機能を達成するオルガノイドを提供し、例えば、本発明は副甲状腺の(parathyroid)オルガノイドを提供する。特別な態様において、前記副甲状腺又は副甲状腺のオルガノイドの少なくとも1の生理的機能は、検出可能な量の副甲状腺ホルモン(PTH)を産生することである。PTHの産生は、例えば、Intact-PTH ELISA Kit(Immuno-Biological Laboratories、Minneapolis、MN)を使用して、前記オルガノイドが培養された培養培地のPTHの存在を試験することによりイン・ビトロ評価分析できる。ある態様において、副甲状腺オルガノイドは、副甲状腺主細胞を含む。更に特別な態様において、副甲状腺オルガノイドは、副甲状腺主細胞及び副甲状腺好酸性細胞の両方を含む。ある態様において、前記オルガノイドは、検出可能な量のPTHを産生するように遺伝子工学的に設計されている細胞を含む(例えば、追加的に含む)。上述の評価分析のそれぞれでは、ある態様において、オルガノイドが培養された培養培地が、前記オルガノイドによる特別なホルモン又はタンパク質の産生のために評価分析される。
副腎腺は、主にエピネフリンの産生に寄与する副腎クロム親和性細胞、ミネラルコルチコイド(主にアルドステロン)を産生する副腎球状帯細胞、糖質コルチコイド(例えば、11-デオキシコルチコステロン、コルチコステロン、及び/又はコルチゾール)を産生する副腎束状帯細胞、及びアンドロゲン(例えば、デヒドロエピアンドロステロン(DHEA)及び/又はアンドロステンジオン)を産生する副腎網状帯細胞を含む。ある態様において、従って、本発明では、副腎腺の少なくとも1の生理的機能を達成するオルガノイドを提供し、例えば、本発明は副腎の(adrenal)オルガノイドを提供する。特別な態様において、前記副腎腺又は副腎腺のオルガノイドの少なくとも1の生理的機能は、検出可能な量の1以上の副腎特異性(adrenal-specific)ホルモン、例えば、1以上のアルドステロン、フルドロコルチゾン、デヒドロエピアンドロステロン、18-ヒドロキシ-11-デオキシコルチコステロン、コルチコステロン、コルチゾール、DHEA及び/又はアンドロステンジオンを産生することである。ある態様において、前記オルガノイドは、検出可能な量の1以上の、例えば、アルドステロン、11-デオキシコルチコステロン、コルチコステロン、コルチゾール、フルドロコルチゾン、DHEA及び/又はアンドロステンジオンを産生するように遺伝子工学的に設計されている細胞を含む(例えば、更に含む)ことができる。
膵臓は、膵臓α細胞、膵臓β細胞、膵臓デルタ細胞、膵臓ポリペプチド(PP)細胞、及び膵臓イプシロン細胞を含む。ある態様において、従って、本発明では、膵臓の少なくとも1の生理的機能を達成するオルガノイドを提供し、例えば、本発明は膵臓の(pancreatic)オルガノイドを提供する。特別な態様において、前記膵臓又は膵臓のオルガノイドの少なくとも1の生理的機能は、検出可能な量の1以上の膵臓特異性ホルモン又はタンパク質、例えば、アミリン(膵島アミロイドポリペプチド、又はIAPP)、インスリン、ソマトスタチン、グレリン(grehlin)、膵臓ポリペプチド、及び/又はグルカゴンを、例えばイン・ビトロで産生することである。更に特別な態様において、前記オルガノイドはインスリン及びアミリンを、約10:1、60:1、70:1、80:1、90:1、100:1、110:1、120:1、130:1、140:1、150:1、160:1、170:1、180:1、190:1又は200:1の割合で、イン・ビトロで産生する。ある態様において、前記オルガノイドは、検出可能な量の1以上のアミリン、インスリン、グルカゴン、ソマトスタチン、グレリン、及び/又は膵臓ポリペプチドを産生するように遺伝子工学的に設計されている細胞を含む(例えば、更に含む)ことができる。
肝臓は、主に、肝臓質量の70%〜80%を構成する実質性肝細胞と、それに伴う脈管内皮細胞及びKupffer細胞を含む。ある態様において、従って、本発明では、肝臓の少なくとも1の生理的機能を達成するオルガノイドを提供し、例えば、本発明は肝臓の(liver)オルガノイドを提供する。
本発明で提供されるオルガノイドは、特別な病気又は障害を患い、例えばタンパク質又はポリペプチド、ホルモン、サイトカイン、インターロイキン、インターフェロン、上記いずれかの受容体等の生体分子の産生等の、生理的機能の交換又は増加により治療可能な個体へ、これら生体分子を産生するオルガノイドを投与する等して、投与された場合に個体内で天然の生体分子を交換又は増加させるような、治療する方法に使用できる。本発明で開示されたいずれかのオルガノイドは、当業者により適切と判断されるような治療的目的に使用できる。
本実施例は、胎盤の脈管マトリックスを実質的に損傷がないように保存するような、胎盤の効率的で優しい脱細胞方法、及び、非胎盤由来細胞による脈管マトリックスの有効な再構築を示す。
本実施例は、追加的ヒト細胞型が、脱細胞化胎盤の脈管足場に注入可能であり、かつ、その中で培養可能であることを示す。
本実施例は、合成材料はバイオプリントされて、制御された線維直径及び孔径の足場を製造できること、これら足場は細胞間マトリックス(ECM)の応用のための適切な基体(substrate)を提供できること、を示す。本実施例は更に、バイオプリントされた合成材料を含む足場及びECM(ハイブリッド足場)は、胎盤幹細胞等の胎盤細胞を含む、付着及び細胞の増殖に適した基体を示す。
胎盤幹細胞は、ハイブリッド足場の表面全体に培養期間中、増殖して拡張していき、培養第6日には、ハイブリッド足場の主な表面を覆った。MTS細胞増殖アッセイは、細胞数は、期間中は顕著に増加したことを示した(図7)。更に、ハイブリッド足場上に播種された胎盤幹細胞は、カルセイン染色(図8)に示されるように、第8日培養期間中良い生存度を示した。それと共に、これらデータは、PCL-ECMハイブリッド足場は細胞の付着、生存、及び増殖をサポートすることを示す。
本実施例は、機能的オルガノイドは、脱細胞化胎盤の脈管足場(DPVS)を使用して設計できることを示す。
本実施例は更に、機能的オルガノイドは、脱細胞化胎盤の脈管足場(DPVS)を使用して設計できることを示す。
本実施例は、DPVS上で培養された細胞は、生存して代謝活性を維持することを示す。
本実施例は、幹細胞の分化をサポートするDPVSの能力を基礎として、脱細胞化ヒト胎盤脈管足場(DPVS)は、組織エンジニアリングのためのプラットフォームとして使用できることを示す。
本実施例は、脱細胞化ヒト胎盤脈管足場(DPVS)は、理想的な細胞培養環境であり、イン・ビボ培養条件を模倣できることを示す。
本実施例は、胎盤葉はDPVSとして使用できることを示す。
本発明の組成物及び方法は、本明細書に記載された特別な態様の範囲に限定されない。実際、本明細書記載の組成物及び方法の様々な修正も更に、当業者には前記記載から明らかである。このような修正も、添付された特許請求の範囲内となることを意図されている。
Claims (194)
成長ホルモン産生細胞、乳腺刺激ホルモン産生細胞、甲状腺刺激ホルモン産生細胞、性腺刺激ホルモン産生細胞、副腎皮質刺激ホルモン産生細胞、下垂体中葉由来の細胞、巨大細胞神経分泌細胞、腸管細胞、気道細胞、甲状腺上皮細胞、傍濾胞細胞、副甲状腺細胞、副甲状腺主細胞、好酸性細胞、副腎腺細胞、クロム親和性細胞、ライディッヒ細胞、内卵胞膜細胞、黄体細胞、顆粒膜黄体細胞、卵胞膜黄体細胞、傍糸球体細胞、緻密斑細胞、極周囲細胞、メサンギウム細胞、
血管及びリンパ管内皮有窓型細胞、血管及びリンパ管内皮連続型細胞、血管及びリンパ管内皮脾細胞、滑膜細胞、漿膜細胞(腹膜の、胸膜の、及び心膜腔の内壁)、扁平上皮細胞、円柱細胞、暗調細胞、前庭膜細胞(耳の内リンパ腔内壁)、血管条基底細胞、血管条周辺細胞(耳の内リンパ腔内壁)、クラウディウス細胞、ベッチェル細胞、脈絡叢細胞、軟膜クモ膜扁平上皮細胞、色素毛様体上皮細胞、非色素毛様体上皮細胞、角膜内皮細胞、栓細胞、
気道繊毛細胞、卵管繊毛細胞、子宮内膜繊毛細胞、精巣網繊毛細胞、精巣輸出管繊毛細胞、繊毛性上衣細胞、
表皮角化細胞、表皮基底細胞、指爪及び足指爪の角化細胞、爪床基底細胞、毛幹の毛髄質細胞、毛幹の毛皮質細胞、毛幹の毛小皮細胞、毛根の毛小皮鞘細胞、毛根ハックスレー層の鞘細胞、毛根ヘンレ層の鞘細胞、外毛根鞘細胞、毛母細胞、
重層扁平上皮の表面上皮細胞、上皮基底細胞、泌尿器上皮細胞、
耳のコルチ器官の内有毛細胞、耳のコルチ器官の外有毛細胞、嗅上皮基底細胞、冷感受性一次感覚ニューロン、熱感受性一次感覚ニューロン、表皮のメルケル細胞、嗅覚受容体神経、痛み感受性一次感覚ニューロン、光受容体桿体細胞、光受容体青色感受性錐体細胞、光受容体緑色感受性錐体細胞、光受容体赤色感受性錐体細胞、固有受容性一次感覚ニューロン、触覚感受性一次感覚ニューロン、I型頸動脈小体細胞、II型頸動脈小体細胞(血液pHセンサ)、内耳前庭器官のI型有毛細胞(加速度及び重力)、内耳前庭器官のII型有毛細胞、I型味蕾細胞、
コリン作動性神経細胞、アドレナリン作動性神経細胞、ペプチド作動性神経細胞、
コルチ器官の内柱細胞、コルチ器官の外柱細胞、コルチ器官の内指骨細胞、コルチ器官の外指骨細胞、コルチ器官の境界細胞、コルチ器官のヘンゼン細胞、前庭器支持細胞、味蕾支持細胞、嗅上皮支持細胞、シュワン細胞、サテライト細胞、腸内グリア細胞、
星状細胞、ニューロン、オリゴデンドロサイト、紡錘形ニューロン、
前水晶体上皮細胞、クリスタリン含有水晶体線維細胞、
肝細胞、含脂肪細胞、白色脂肪細胞、褐色脂肪細胞、肝臓脂肪細胞、
腎臓糸球体壁細胞、腎臓糸球体有足細胞、腎臓近位尿細管刷子縁細胞、ヘンレ係蹄の細い部分の細胞、腎臓遠位尿細管細胞、腎臓集合管細胞、I型肺胞上皮細胞、膵管細胞、非線条導管細胞、導管細胞、腸刷子縁細胞、外分泌腺線条導管細胞、胆嚢上皮細胞、精巣輸出管非繊毛細胞、精巣上体主細胞、精巣上体基底細胞、
エナメル芽細胞上皮細胞、半月面上皮細胞、コルチ器官歯間上皮細胞、疎性結合組織線維芽細胞、角膜実質細胞、腱線維芽細胞、骨髄網状組織線維芽細胞、非上皮性線維芽細胞、周細胞、髄核細胞、セメント芽細胞/セメント細胞、造歯細胞、象牙芽細胞、ヒアリン軟骨細胞、線維軟骨細胞、弾性軟骨細胞、骨芽細胞、骨細胞、破骨細胞、骨前駆細胞、硝子体細胞、星細胞(耳)、肝星細胞(伊東細胞)、膵星細胞、
赤色骨格筋細胞、白色骨格筋細胞、中間体骨格筋細胞、筋紡錘の核袋細胞、筋紡錘の核鎖細胞、サテライト細胞、通常の心筋細胞、結節性心筋細胞、プルキンエ線維細胞、平滑筋細胞、虹彩の筋上皮細胞、外分泌腺の筋上皮細胞、
網状赤血球、巨核球、単球、結合組織マクロファージ、表皮ランゲルハンス細胞、樹状細胞、ミクログリア細胞、好中球、好酸球、好塩基球、マスト細胞、ヘルパーT細胞、サプレッサーT細胞、細胞傷害性T細胞、ナチュラルキラーT細胞、B細胞、ナチュラルキラー細胞、
メラニン形成細胞、網膜色素上皮細胞、
卵原細胞/卵母細胞、***細胞、***細胞、精原細胞、***、卵胞細胞、セルトリ細胞、胸腺上皮細胞、及び/又は間質性腎臓細胞を含む、請求項29記載のオルガノイド。
前記遺伝子的障害若しくは病気は多発性嚢胞腎疾患であって、前記タンパク質はポリシスチン1(PKD1)、PKD-2若しくはPKD3であるか、又は、
前記遺伝子的障害若しくは病気はフェニルケトン尿症であって、前記タンパク質はフェニルアラニンヒドロキシラーゼである、請求項67記載のオルガノイド。
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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JP2019136011A (ja) * | 2018-02-15 | 2019-08-22 | 学校法人自治医科大学 | 脱細胞化担体製造方法、脱細胞化担体、細胞充填方法、細胞シート作製方法、及び脱細胞化溶液キット |
JP2021522831A (ja) * | 2018-05-14 | 2021-09-02 | ユーシーエル ビジネス リミテッド | 組織脱細胞化の方法 |
WO2021251312A1 (ja) * | 2020-06-08 | 2021-12-16 | 国立大学法人 東京医科歯科大学 | 細胞培養方法 |
JP2022002536A (ja) * | 2016-02-12 | 2022-01-11 | ユニバーシティ・オブ・オタワ | 植物及び真菌由来の脱細胞化された細胞壁構造並びに足場材料としてのその使用 |
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Families Citing this family (55)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9719068B2 (en) | 2010-05-06 | 2017-08-01 | Children's Hospital Medical Center | Methods and systems for converting precursor cells into intestinal tissues through directed differentiation |
JP2015528353A (ja) * | 2012-09-04 | 2015-09-28 | アントフロゲネシス コーポレーション | 組織製造方法 |
US11229789B2 (en) | 2013-05-30 | 2022-01-25 | Neurostim Oab, Inc. | Neuro activator with controller |
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CN117417831B (zh) * | 2023-12-18 | 2024-02-27 | 芯潮澎湃生物科技(南京)有限公司 | 一种免疫共培养类器官芯片模型 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009539378A (ja) * | 2006-06-09 | 2009-11-19 | アントフロゲネシス コーポレーション | 胎盤環境及び幹細胞を培養するためのその使用 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1061812C (zh) * | 1996-04-01 | 2001-02-14 | 胡杰 | 制备皮肤移植体的方法 |
EP1367892B1 (en) * | 2001-02-14 | 2013-10-30 | Anthrogenesis Corporation | Renovation and repopulation of decellularized tissues and cadaveric organs by stem cells |
CA2464460A1 (en) * | 2001-10-23 | 2003-05-01 | Eduardo N. Mitrani | In vitro micro-organs, and uses related thereto |
US20030187515A1 (en) * | 2002-03-26 | 2003-10-02 | Hariri Robert J. | Collagen biofabric and methods of preparing and using the collagen biofabric |
CA2533259C (en) * | 2003-07-21 | 2014-01-28 | Lifecell Corporation | Acellular tissue matrices made from galactose .alpha.-1,3-galactose-deficient tissue |
US20060282173A1 (en) * | 2004-03-09 | 2006-12-14 | Mcfetridge Peter S | Substantially decellularized grafts from umbilical cord vessels and process for preparing and using same |
AU2006311482B2 (en) * | 2005-11-08 | 2011-08-25 | Georgia Tech Research Corporation | Acellularized biomaterial from embryonic stem cells |
EP3011962B1 (en) * | 2007-07-10 | 2018-12-05 | LifeCell Corporation | Acellular tissue matrix compositions for tissue repair |
NZ617412A (en) * | 2007-09-28 | 2015-06-26 | Anthrogenesis Corp | Tumor suppression using human placental perfusate and human placenta-derived intermediate natural killer cells |
WO2009102484A2 (en) * | 2008-02-14 | 2009-08-20 | Wake Forest University Health Sciences | Inkjet printing of tissues and cells |
WO2011072393A1 (en) * | 2009-12-17 | 2011-06-23 | Queen's University At Kingston | Decellularized adipose tissue |
-
2012
- 2012-12-21 WO PCT/US2012/071192 patent/WO2013096741A2/en active Application Filing
- 2012-12-21 EP EP12860504.5A patent/EP2793912B1/en active Active
- 2012-12-21 US US14/367,631 patent/US20150017140A1/en not_active Abandoned
- 2012-12-21 CA CA2859714A patent/CA2859714C/en active Active
- 2012-12-21 JP JP2014548937A patent/JP2015510391A/ja active Pending
- 2012-12-21 CN CN202110850442.5A patent/CN113699105A/zh active Pending
- 2012-12-21 CN CN201280070203.7A patent/CN104411318A/zh active Pending
-
2015
- 2015-04-24 HK HK15103985.4A patent/HK1203380A1/xx unknown
-
2016
- 2016-06-15 US US15/182,804 patent/US20170128625A1/en not_active Abandoned
-
2018
- 2018-11-05 JP JP2018207829A patent/JP2019050814A/ja active Pending
-
2020
- 2020-11-13 JP JP2020189093A patent/JP2021048846A/ja not_active Withdrawn
-
2022
- 2022-10-17 JP JP2022165987A patent/JP2023015063A/ja active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009539378A (ja) * | 2006-06-09 | 2009-11-19 | アントフロゲネシス コーポレーション | 胎盤環境及び幹細胞を培養するためのその使用 |
Non-Patent Citations (6)
Title |
---|
ANNU.REV.BIOMED.ENG.,2011,13,P.27-53, JPN6016040880, ISSN: 0003633820 * |
BIOMATERIALS,2007,28(26),P.3834-42, JPN6016040874, ISSN: 0003633816 * |
BIOMATERIALS,2008,29(12),P.1862-71, JPN6016040876, ISSN: 0003633817 * |
CELL TRANSPLANT.,2010,19(6),P.655-65, JPN6016040879, ISSN: 0003633819 * |
J.BIOMED.MATER.RES.A,2006,79(2),P.359-69, JPN6016040877, ISSN: 0003633818 * |
TISSUE ENG.PART C METHODS,2010,16(5),P.1041-50, JPN6016040881, ISSN: 0003633821 * |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018533931A (ja) * | 2015-10-02 | 2018-11-22 | ウェイク・フォレスト・ユニヴァーシティ・ヘルス・サイエンシズ | がん転移をモデル化するためのin vitroでの方法および装置 |
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JP7174984B2 (ja) | 2018-02-15 | 2022-11-18 | 学校法人自治医科大学 | 脱細胞化担体製造方法、脱細胞化担体保存方法、細胞充填方法、細胞シート作製方法、及び脱細胞化溶液キット |
JP2021522831A (ja) * | 2018-05-14 | 2021-09-02 | ユーシーエル ビジネス リミテッド | 組織脱細胞化の方法 |
US12038432B2 (en) | 2019-02-01 | 2024-07-16 | Wake Forest University Health Sciences | Organoids related to immunotherapy and methods of preparing and using the same |
WO2021251312A1 (ja) * | 2020-06-08 | 2021-12-16 | 国立大学法人 東京医科歯科大学 | 細胞培養方法 |
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US20170128625A1 (en) | 2017-05-11 |
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