JP2021090448A - 哺乳動物肝細胞の成熟 - Google Patents
哺乳動物肝細胞の成熟 Download PDFInfo
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- JP2021090448A JP2021090448A JP2021032236A JP2021032236A JP2021090448A JP 2021090448 A JP2021090448 A JP 2021090448A JP 2021032236 A JP2021032236 A JP 2021032236A JP 2021032236 A JP2021032236 A JP 2021032236A JP 2021090448 A JP2021090448 A JP 2021090448A
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Abstract
Description
前記肝細胞を、Srcキナーゼ阻害剤、前駆体、代謝産物と類似体を含むビタミンD、低酸素誘導化合物、スフィンゴシンとスフィンゴシン誘導体、ペルオキシソーム増殖因子活性化受容体(PPAR)の活性化因子、血小板活性化因子(PAF)、PKC阻害剤、及びそれらの組み合わせからなる群から選択された少なくとも1つの成熟因子に暴露することを含む方法。
哺乳動物肝前駆細胞を分化条件下で培養して肝細胞を得ることと、
前記肝細胞を、Srcキナーゼ阻害剤、前駆体、代謝産物と類似体を含むビタミンD、低酸素誘導化合物、スフィンゴシンとスフィンゴシン誘導体、ペルオキシソーム増殖因子活性化受容体(PPAR)の活性化因子、血小板活性化因子(PAF)、PKC阻害剤、及びそれらの組み合わせからなる群から選択された、からなる群から選択された少なくとも1つの成熟因子に暴露すること
を含む方法。
前記ヒト肝細胞などの前記哺乳動物肝細胞を、Srcキナーゼ阻害剤、前駆体、代謝産物と類似体を含むビタミンD、低酸素誘導化合物、スフィンゴシンとスフィンゴシン誘導体、ペルオキシソーム増殖因子活性化受容体(PPAR)の活性化因子、血小板活性化因子(PAF)、PKC阻害剤、及びそれらの組み合わせからなる群から選択された、少なくとも1つの成熟因子に暴露するステップ
を含むものとして説明されることができる。
ヒト肝前駆細胞などの哺乳動物肝前駆細胞を分化条件下で培養して肝細胞を得るステップと、
前記肝細胞を、Srcキナーゼ阻害剤、前駆体、代謝産物と類似体を含むビタミンD、低酸素誘導化合物、スフィンゴシンとスフィンゴシン誘導体、ペルオキシソーム増殖因子活性化受容体(PPAR)の活性化因子、血小板活性化因子(PAF)、PKC阻害剤、及びそれらの組み合わせからなる群から選択された、からなる群から選択された少なくとも1つの成熟因子に暴露するステップ
を含むものとして説明されることができる。
ここで使用される「多能性の」又は「多能性」は、3つの胚葉(内胚葉、中胚葉、及び外胚葉)のすべてのタイプの特殊細胞を形成する可能性を指し、「全能性の」又は「全能性」、すなわち子孫を生じさせることができる完全な胚を形成する能力とは区別される。
すべてのhPS細胞(上記で定義した)は、本発明のための出発材料として使用することができる。以下の実施例では、特に、肝細胞は、mEFフィーダー細胞上に確立された未分化ヒト胚性幹細胞(hESC)からインビトロで誘導され(Heins et al. 2004)、フィーダーフリー条件下で維持された。この実験に使用される細胞株は、hES細胞株であるSA121、SA167、SA181、SA461(セルアーティス社、ヨーテボリ、スウェーデン)であってもよいがそれらに限定されず、それらは、Heins et al. 2004及びCaisander et al. 2006によって説明されているように増殖することができる。
肝細胞は、以下の例示的な基本的プロトコルAとBを使用することによって、hPS細胞から得てもよい。
未分化hPS細胞を解離させ、0日目にフィブロネクチンベースのコーティング上に直接播種する。異なる培地を新たに調製し、0、1、2、3、4、5、7日目、その後、2又は3日ごとに、肝臓前段階、分化及び成熟期に追加した。
前処理媒体
3μM CHIR99021
5μM ROCK阻害剤
1日目
RPMI 1640(+0.1%PEST+1%グルタマックス)
1×B27
50ng/mlアクチビンA
3μM CHIR99021
5μM LY294002
3μM CHIR99021
2日目
RPMI 1640(+0.1%PEST+1%グルタマックス)
1×B27
50ng/mlアクチビンA
5μM LY294002
10nM 5-アザ-2-デオキシシチジン
3日目
RPMI 1640(+0.1%PEST+1%グルタマックス)
1×B27
50ng/mlアクチビンA
4〜7日目
RPMI 1640(+0.1%PEST+1%グルタマックス)
1×B27
50ng/mlアクチビンA
ノックアウト-DMEM+1%PEST+1%グルタマックス
20%ノックアウト血清交換
1%非必須アミノ酸(NEAA)
0.2%ベータメルカプトエタノール
1%DMSO
14〜45日目(分化と成熟)
WME+1%グルタマックス+0.1%PEST
0.55mg/mL BSA-FAF
0.025mg/mLアスコルビン酸
0.67μg/mLヒドロコルチゾンヘミコハク酸塩
10μg/mLトランスフェリン
5μg/mLインスリン
0.003μg/mL EGF
0.1μM DexM
10ng/ml OsM
20ng/ml HGF
0.5%DMSO
1.4μM BIO
0.5μMケンパロン
0.2μM 9シスレチノイン酸
未分化hPS細胞を解離させ、0日目にフィブロネクチンベースのコーティング上に直接播種する。異なる培地を新たに調製し、0、1、2、3、4、5、7日目、その後、2又は3日ごとに、肝臓前段階、分化及び成熟期に追加した。
前処理媒体
3μM CHIR99021
5μM ROCK阻害剤
1日目
RPMI 1640(+0.1%PEST+1%グルタマックス)
1×B27
50ng/mlアクチビンA
3μM CHIR99021
5μM LY294002
3μM CHIR99021
2日目
RPMI 1640(+0.1%PEST+1%グルタマックス)
1×B27
50ng/mlアクチビンA
5μM LY294002
10nM 5-アザ-2-デオキシシチジン
3日目
RPMI 1640(+0.1%PEST+1%グルタマックス)
1×B27
50ng/mlアクチビンA
4〜7日目
RPMI 1640(+0.1%PEST+1%グルタマックス)
1×B27
50ng/mlアクチビンA
ノックアウト-DMEM+1%PEST+1%グルタマックス
20%ノックアウト血清交換
1%非必須アミノ酸(NEAA)
0.2%ベータメルカプトエタノール
1%DMSO
14〜45日目(分化と成熟)
WME+1%グルタマックス+0.1%PEST
0.55mg/mL BSA-FAF
0.025mg/mLアスコルビン酸
0.67μg/mLヒドロコルチゾンヘミコハク酸塩
10μg/mLトランスフェリン
5μg/mLインスリン
0.003μg/mL EGF
0.1μM DexM
10ng/ml OsM
20ng/ml HGF
0.5%DMSO
1.4μM BIO
0.5μMケンパロン
0.2μM 9シスレチノイン酸
手順:
基本プロトコルAに続いて、フィブロネクチンベースのコーティング上で培養したhiPS細胞由来肝細胞を、分化プロトコルの21日以降、0.5又は5μMの10Z-ヘプタデセン酸、0.5又は5μMのアラキドン酸、5μMのカルシフェジオール、5μMのカルシトリオール、0.2又は0.5μMのコレカルシフェロール、5又は50μMのCGP 52608、0.5又は5μMのドコサヘキサエン酸、0.5、1.25、2.5、5又は10μMのPP1、0.5又は5μMのPP2、0.5又は5μMのD-エリスロ-スフィンゴシン、或いは0.5又は5μMのテトラデカン酸により処理した(図1)。
図1A〜U)10Z-ヘプタデセン酸、アラキドン酸、カルシフェンジオール、カルシトリオール、コレカルシフェロール、CGP 52608、ドコサヘキサエン酸、PP1、PP2、D-エリスロ-スフィンゴシン、及びテトラデカン酸は、hiPS細胞由来肝細胞のCYP活性レベルを、分化プロトコルの29日目と36日目の両方において増加させる。いくつかのケースでは、2B6活性レベルが検出レベル未満であった。
手順:
基本プロトコルBに続いて、コラーゲンI−フィブロネクチンベースのコーティング上で培養したChiPSC-4由来肝細胞を、分化プロトコルの21日以降、0.5μMの10Z-ヘプタデセン酸、0.5μMのアラキドン酸、0.5μMのカルシトリオール、5μMのCGP 52608、0.2μMのコレカルシフェロール、5μMのPP1、0.5μMのD-エリスロ-スフィンゴシン、0.2μMの13シス-RA、0.5μMのL-エリスロMAPP、0.5μMのPAF C16、0.5μMのC16セラミド、又はそれらの化合物の異なった組み合わせにより処理した(図2)。
図2A〜D)10Z-ヘプタデセン酸(10Z)、アラキドン酸(Ara)、カルシトリオール(Caltr)、コレカルシフェロール(Chole)、CGP 52608(CGP)、PP1、D-エリスロ-スフィンゴシン(Sph)、13シス-RA(13シス)、L-エリスロMAPP(MAPP)、PAF C16(PAF)、C16セラミド(Cera)、又はそれらの化合物の異なった組み合わせは、hiPS細胞由来肝細胞のCYP活性レベルを、分化プロトコルの29日目において増加させる。いくつかのケースでは、2B6活性レベルが検出レベル未満であった。
手順:
基本プロトコルBに続いて、コラーゲンI−フィブロネクチンベースのコーティング上で培養したChiPSC-4由来肝細胞を、分化プロトコルのそれぞれ11、14、21、25及び28日以降に開始して、0.5μMの10Z-ヘプタデセン酸、0.5μMのアラキドン酸、0.5μMのカルシトリオール、5μMのCGP 52608、0.2μMのコレカルシフェロール、5μMのPP1、及び0.5μMのD-エリスロ-スフィンゴシンにより処理した(図3)。
図3A、B)分化プロトコルの11日目と28日目の間に開始した、10Z-ヘプタデセン酸(10Z)、アラキドン酸(Ara)、カルシトリオール(Caltr)、コレカルシフェロール(Chole)、CGP 52608(CGP)、PP1、及びD-エリスロ-スフィンゴシン(Sph)による処理は、hiPS細胞由来肝細胞のCYP活性レベルを、分化プロトコルの29日目と36日目において増加させる。
手順:
基本プロトコルBに続いて、hiPS細胞株のChiPSC4、ChiPSC6b、ChiPSC22、P11015、P11021、P11032と、hES細胞株のSA121に由来する肝細胞を、コラーゲンI−フィブロネクチンベースのコーティング上で培養し、分化プロトコルの21日以降、0.5μMの10Z-ヘプタデセン酸、0.5μMのアラキドン酸、0.5μMのカルシトリオール、5μMのCGP 52608、0.2μMのコレカルシフェロール、5μMのPP1、及び0.5μMのD-エリスロ-スフィンゴシンの組み合わせにより処理した(図4)。
図4A〜G)10Z-ヘプタデセン酸(10Z)、アラキドン酸(Ara)、カルシトリオール(Caltr)、コレカルシフェロール(Chole)、CGP 52608(CGP)、PP1、及びD-エリスロ-スフィンゴシン(Sph)による処理は、hiPS細胞株のChiPSC4(A)、ChiPSC6b(B)、ChiPSC22(C)、P11015(D)、P11021(E)、P11032(F)と、hES細胞株のSA121(G)に由来する肝細胞のCYP活性レベルを、分化プロトコルの29日目において増加させる。
手順:
基本プロトコルBに続いて、hiPS細胞株のChiPSC18に由来する肝細胞を、コラーゲンI−フィブロネクチンベースのコーティング上で培養し、分化プロトコルの21日以降、0.5μMの10Z-ヘプタデセン酸、0.5μMのアラキドン酸、0.5μMのカルシトリオール、5μMのCGP 52608、0.2μMのコレカルシフェロール、5μMのPP1、及び0.5μMのD-エリスロ-スフィンゴシンの組み合わせにより、オンコスタチンM及び/又はHGFの存在下と非存在下で処理した(図5)。
図5A、B)10Z-ヘプタデセン酸、アラキドン酸、カルシトリオール、コレカルシフェロール、CGP 52608、PP1、及びD-エリスロ-スフィンゴシンにより、オンコスタチンM及び/又はHGFの存在下と非存在下での処理の結果、分化プロトコルの31日目における、hiPS細胞株のChiPSC18に由来する肝細胞のCYP活性レベルは同様になる。
Chen, Y.F. et al. (2012) Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol. Hepatology. 2012 55(4):1193-203
Chung, Y. et al. (2008) Human Embryonic Stem Cell Lines Generated without Embryo Destruction. doi: 10.1016/j.stem.2007.12.013
Duan, Y. et al. Differentiation and characterization of metabolically functioning hepatocytes from human embryonic stem cells. Stem Cells. 28(4):674-86
Dunn, J et al. (1991) Long-term in Vitro function of adult hepatocytes in a collagen sandwich configuration. Biotechnol.Prog. 7:237-245
D'Amour K.A. et al. (2005) Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnology. 23(12):1534-41.
Funakoshi, N. et al. (2011) Comparison of hepatic-like cell production from human embryonic stem cells and adult liver progenitor cells: CAR transduction activates a battery of detoxification genes. Stem Cell Rev. 7(3):518-31
Hay, D. et al (2007) Direct differentiation of human embryonic stem cells to hepatocyte-like cells exhibiting functional activities. Cloning Stem Cells. 2007 Spring;9(1):51-62. Erratum in: Cloning Stem Cells. 2009 Mar;11(1):209.
Hay, D. et al (2008) Efficient differentiation of hepatocytes from human embryonic stem cells exhibiting markers recapitulating liver development in vivo. Stem Cells. Apr;26(4):894-902.
Heins, N. et al (2004) Derivation, characterization, and differentiation of human embryonic stem cells. Stem Cells. 22(3):367-76.
Klimanskaya, I. et al (2006) Human embryonic stem cell lines derived from single blastomeres. Nature, Nov 23; 444(7118):481-5. Epub 2006 Aug 23. Erratum in: Nature. 2006 Nov 23;444(7118):512. Nature. 2007 Mar 15;446(7133):342.
Martin M. et al (2005) Human embryonic stem cells express an immunogenic nonhuman sialic acid. Nat Med. Feb;11(2):228-32.
Mercader, A. et al (2009) Human Embryo Culture. Essential Stem Cell Methods, Chapter 16, Academic Press, 1st Edition, Eds. Lanza, R. and Klimanskaya, I.
Page, J et al. (2007) Gene expression profiling of extracellular matrix as an effector of human hepatocyte phenotype in primary cell culture. Tox.Sci. 97(2):384-397
Si-Tayeb, K. et al. (2010) Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells Hepatology. 51(1):297-305.
Song. Z. et al. (2009) Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells. Cell Res. 19(11):1233-42
Sullivan, G.J. et al. (2010) Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology. 51(1):329-35.
Siller, R. et al. (2015) Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells. Stem Cell Reports 4(5):939-52.
Takahashi, K. et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell Nov 30;131(5):861-72.
Thomson, J. et al. (1998) Embryonic stem cell lines derived from human blastocysts.
Science. Nov 6;282(5391):1145-7. Erratum in: Science 1998 Dec 4;282(5395):1827.
Turner, R. et al. (2011) Human hepatic stem cell and maturational liver lineage biology. Hepatology. 53(3):1035-45
Wang, Y. et al. (2011) Lineage restriction of human hepatic stem cells to mature fates is made efficient by tissue-specific biomatrix scaffolds. Hepatology. 53(1):293-305.
Yu, J. and Thomson, J. (2009) Induced Puripotent Stem Cell Derivation. Essentials of Stem Cell Biology, Chapter 37, Academic Press, 2nd Edition (2009), Eds. Lanza, R. et al.
Zhou H. et al (2009). Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell. 4(5):381-4.
Claims (16)
- Srcキナーゼ阻害剤、前駆体、代謝産物と類似体を含むビタミンD、低酸素誘導化合物、スフィンゴシンとスフィンゴシン誘導体、ペルオキシソーム増殖因子活性化受容体(PPAR)の活性化因子、血小板活性化因子(PAF)、PKC阻害剤、及びそれらの組み合わせからなる群から選択される少なくとも2つの成熟因子を含む、組成物。
- 前記組成物が、少なくとも1つのSrcキナーゼ阻害剤、並びに、前駆体、代謝産物と類似体を含むビタミンD、低酸素誘導化合物、スフィンゴシンとスフィンゴシン誘導体、ペルオキシソーム増殖因子活性化受容体(PPAR)の活性化因子、血小板活性化因子(PAF)、及びPKC阻害剤からなる群から選択されるさらなる少なくとも1つの成熟因子を含む、請求項1に記載の組成物。
- 前記Srcキナーゼ阻害剤が、PP1、PP2、1-NA-PP1、1-NM-PP1、Src阻害剤-1(Src-I1)、Srcキナーゼ阻害剤I、Srcキナーゼ阻害剤II、A-419529、A-770041、AZM475271、ボスチニブ、CGP77675、ダムナカンタル、ダサチニブ、ダサチニブ一水和物、ER27319マレイン酸塩、フィンゴリモド(FTY720)、ゲルダナマイシン、ハービマイシンA、KB SRC4、KX2-391、KX1-004、ラベンダスチンA、ラベンダスチンC、LCK阻害剤2、Lynペプチド阻害剤、MLR-1023、MNS、N-アセチル-O-ホスホノ-Tyr-Glu ジペンチルアミド、N-アセチル-O-ホスホノ-Tyr-Glu-Glu-Ile-Glu、NVP-BHG712、PD166285、PD173952、PD180970、ピセアタノール、pp60 c-src、ケルセチン、ジヘテロスポラ・クラミドスポリア固体由来のラディシコール、サラカチニブ、SU6656、TC-S7003、TG100572、WH-4-023、ZM306416、及びそれらの組み合わせからなる群から選択される、請求項1又は2に記載の組成物。
- 前記少なくとも1つのSrcキナーゼ阻害剤がPP1である、請求項2又は3に記載の組成物。
- 前記組成物が、少なくとも1つのビタミンD、ビタミンD前駆体、ビタミンD代謝物又はビタミンD類似体である、請求項2〜4のいずれか一項に記載の組成物。
- 前記ビタミンDが、コレカルシフェロール、カルシフェジオール、カルシトリオール、及びそれらの組み合わせからなる群から選択される少なくとも1つのビタミンD3である、請求項5に記載の組成物。
- 前記組成物が、CGP52608、CGP52608類似体、メラトニン、メラトニン類似体、コレステロール、コレステロール誘導体、及びそれらの組み合わせからなる群から選択されるRAR関連オーファン受容体アルファ(ROR-アルファ)リガンド、CoCl2、並びにNaN3からなる群から選択される少なくとも1つの低酸素誘導化合物を含む、請求項2〜6のいずれか一項に記載の組成物。
- 前記組成物が、スフィンゴシン又はスフィンゴシン誘導体を含む、請求項2〜7のいずれか一項に記載の組成物。
- 前記スフィンゴシンが、D-エリスロ-スフィンゴシンである、請求項8に記載の組成物。
- 前記組成物が、チアゾリジンジオン、遊離脂肪酸(FFA)、エイコサノイド前駆体とエイコサノイド類似体を含むエイコサノイド、及びそれらの組み合わせからなる群から選択される少なくとも1つのペルオキシソーム増殖因子活性化受容体(PPAR)の活性化因子を含む、請求項2〜9のいずれか一項に記載の組成物。
- 前記遊離脂肪酸(FFA)が、ドデカン酸、トリデカン酸、テトラデカン酸、ペンタデカン酸、ヘキサデカン酸、ヘプタデカン酸、エイコサン酸、ヘンエイコサン酸、ドコサン酸、トリコサン酸、テトラコサン酸、ペンタコサン酸、ヘキサコサン酸、及びそれらの組み合わせからなる群から選択される、請求項10に記載の組成物。
- 前記エイコサノイド、エイコサノイド前駆体又はエイコサノイド類似体が、ジアシルグリセロール、エイコサペンタエン酸、ジホモガンマリノレン酸、アラキドン酸、ETYA(5,8,11,14-エイコサテトライン酸)、5-HETEと15-HETEを含むヒドロキシエイコサテトラエン酸(HETE)ファミリーのメンバー、9-HODEと13-HODEを含むヒドロキシオクタデカジオン酸(HODE)ファミリーのメンバー、古典的エイコサノイド、及び非古典的エイコサノイドからなる群から選択される、請求項10又は11に記載の組成物。
- 前記組成物が、少なくとも1つの血小板活性化因子(PAF)を含む、請求項2〜12のいずれか一項に記載の組成物。
- 前記組成物が、ビスインドリルマレイミドI、ビスインドリルマレイミドII、ビスインドリルマレイミドIII、ビスインドリルマレイミドV、ビスインドリルマレイミドVI、ビスインドリルマレイミドVII、ビスインドリルマレイミドVIII、ビスインドリルマレイミドX、HBDDE、ロトレリン、パルミトイル-DL-カルニチン、R-ステアロイルカルニチンクロライド、ピセアタノール、H-9,H-8,1-(5-イソキノリンスルホニル)-3-メチルピペラジン、HA-100二塩酸塩、HA-1004、HA-1077、5-ヨードツベリシジン、Ro-32-0432、Ro-31-7549、エンザスタウリン(LY317615)、ソトラスタウリン、塩化デクアリニウム、Go 6976、Go 6983、Go 7874、ミリシトリン、4-ヒドロキシタモキシフェン、N-デスメチルタモキシフェンHCl、サフィンゴール、フロレチン、UCN-01、7-オキソスタウロスポリン、K-252a、K-252b、K-252c、メリチン、ヒスピジン、カルホスチンC、エラグ酸、PKC阻害ペプチド19-31、PKC阻害ペプチド19-36、PKCイプシロン転位阻害剤II、EGF-R断片651-658、PKCベータ阻害剤(CAS 257879-35-9)、PKC20-28、PKCβ II/EGFR阻害剤(CAS 145915-60-2)、PKCθ偽基質阻害剤、PKCθ/δ阻害剤、[Ala107]-MBP(104-118)、[Ala113]-MBP(104-118)、ZIP、C-1、ブリオスタチン1、LY333531塩酸塩、CGP53535、ケレリトリンクロライド、TCS21311、CID755673、ゴシポール、ET-18-OCH3、1-O-ヘキサデシル-2-O-メチル-rac-グリセロール、NPC-15437二塩酸塩、NGIC-I、MDL-27,032、DAPH-7,7-アミノインドール、5-アミノ-2-メチルインドール、rac-2-メトキシ-3-ヘキサデカンアミド-1-プロピルホスホコリン、銅ビス-3,5-ジイソプロピルサリチレート、D,L-3,4-ジヒドロキシマンデル酸、rac-3-オクタデカンアミド-2-メトキシプロパン-1-オールホスホコリン、KRIBB3、イルモホシン、rac-2-メトキシ-3-ヘキサデカンアミド-1-プロピルホスホコリン、及びそれらの組み合わせからなる群から選択される少なくとも1 つのPKC阻害剤を含む、請求項2〜13のいずれか一項に記載の組成物。
- 請求項1〜14のいずれか一項に記載の組成物を含む培養培地。
- 請求項1〜14のいずれか一項に記載の組成物、又は請求項15に記載の培養培地を含み、任意に、少なくとも1つの細胞外マトリックス(ECM) 成分又はECM成分混合物を含む、キット。
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Publication number | Priority date | Publication date | Assignee | Title |
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WO2011140441A2 (en) | 2010-05-06 | 2011-11-10 | Children's Hospital Medical Center | Methods and systems for converting precursor cells into intestinal tissues through directed differentiation |
CA2949834A1 (en) | 2014-05-28 | 2015-12-03 | James Macormack Wells | Methods and systems for converting precursor cells into gastric tissues through directed differentiation |
WO2016061464A1 (en) | 2014-10-17 | 2016-04-21 | Children's Hospital Center, D/B/A Cincinnati Children's Hospital Medical Center | In vivo model of human small intetine using pluripotent stem cells and methods of making and using same |
EP3452578B1 (en) | 2016-05-05 | 2022-08-10 | Children's Hospital Medical Center | Methods for the in vitro manufacture of gastric fundus tissue and compositions related to same |
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050037493A1 (en) * | 2000-04-27 | 2005-02-17 | Ramkumar Mandalam | Protocols for making hepatocytes from embryonic stem cells |
WO2008115390A2 (en) * | 2007-03-16 | 2008-09-25 | The Hamner Institutes For Health Sciences | Methods of using defensins to treat diabetes |
US20100143313A1 (en) * | 2008-12-10 | 2010-06-10 | The General Hospital Corporation | Homogeneous differentiation of hepatocyte-like cells from embryonic stem cells |
US20120177631A1 (en) * | 2011-01-10 | 2012-07-12 | Morteza Naghavi | Composition for Health Promoting Compounds |
WO2014083132A1 (en) * | 2012-11-29 | 2014-06-05 | Cellectis Sa | Maturation of hepatocyte-like cells derived from human pluripotent stem cells |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050095703A1 (en) | 2001-12-28 | 2005-05-05 | Henrik Semb | Method for the establishment of a pluripotent human blastocyst - derived stem cell line |
AU2003228348A1 (en) * | 2002-03-20 | 2003-10-08 | John T. Fassett | Induction of hepatocyte proliferation in vitro by inhibition of cell cycle inhibitors |
JP5426073B2 (ja) | 2003-05-08 | 2014-02-26 | セルアーティス アーベー | ヒト胚盤胞由来幹細胞(hBS細胞)のフィーダー支持からフィーダーなしの培養系への効率的な移送方法 |
WO2007042225A2 (en) | 2005-10-07 | 2007-04-19 | Cellartis Ab | A method for obtaining a xeno-free hbs cell line |
WO2007143117A2 (en) | 2006-06-02 | 2007-12-13 | Geron Corporation | Differentiation of primate pluripotent cells to hepatocyte-lineage cells |
JP2009539358A (ja) | 2006-06-04 | 2009-11-19 | セルアーティス アーベー | hBS細胞に由来する新規な肝細胞様細胞及び肝芽細胞様細胞 |
US20100190202A1 (en) | 2007-07-20 | 2010-07-29 | Cellartis Ab | Novel population of hepatocytes derived via definitive endoderm (de-hep) from human blastocysts stem cells |
US20120021519A1 (en) | 2008-09-19 | 2012-01-26 | Presidents And Fellows Of Harvard College | Efficient induction of pluripotent stem cells using small molecule compounds |
JP5897543B2 (ja) | 2010-03-22 | 2016-03-30 | セルアーティス アーベー | Wntシグナル経路の調節による多能性細胞から肝細胞様細胞への分化誘導と成熟 |
WO2012036344A1 (ko) * | 2010-09-17 | 2012-03-22 | 한국식품연구원 | 특정 화합물을 유효성분으로 포함하는 식욕억제 식품성분 조성물 |
US20130071931A1 (en) | 2011-08-02 | 2013-03-21 | National Cancer Center | Process for hepatic differentiation from induced hepatic stem cells, and induced hepatic progenitor cells differentiated thereby |
WO2014083133A1 (en) * | 2012-11-29 | 2014-06-05 | Cellectis Sa | Improved methods for producing mammalian pluripotent stem cell-derived endodermal cells |
-
2016
- 2016-06-03 EP EP21161461.5A patent/EP3878947A3/en not_active Withdrawn
- 2016-06-03 US US15/578,899 patent/US10913932B2/en active Active
- 2016-06-03 WO PCT/EP2016/062670 patent/WO2016193441A2/en unknown
- 2016-06-03 JP JP2017558431A patent/JP6847048B2/ja active Active
- 2016-06-03 EP EP20188657.9A patent/EP3760708A1/en not_active Withdrawn
- 2016-06-03 EP EP16728660.8A patent/EP3303566B1/en active Active
-
2020
- 2020-10-09 US US17/066,546 patent/US20210032593A1/en not_active Abandoned
-
2021
- 2021-03-02 JP JP2021032236A patent/JP2021090448A/ja active Pending
- 2021-03-09 US US17/196,063 patent/US20210189332A1/en not_active Abandoned
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050037493A1 (en) * | 2000-04-27 | 2005-02-17 | Ramkumar Mandalam | Protocols for making hepatocytes from embryonic stem cells |
WO2008115390A2 (en) * | 2007-03-16 | 2008-09-25 | The Hamner Institutes For Health Sciences | Methods of using defensins to treat diabetes |
US20100143313A1 (en) * | 2008-12-10 | 2010-06-10 | The General Hospital Corporation | Homogeneous differentiation of hepatocyte-like cells from embryonic stem cells |
US20120177631A1 (en) * | 2011-01-10 | 2012-07-12 | Morteza Naghavi | Composition for Health Promoting Compounds |
WO2014083132A1 (en) * | 2012-11-29 | 2014-06-05 | Cellectis Sa | Maturation of hepatocyte-like cells derived from human pluripotent stem cells |
Non-Patent Citations (4)
Title |
---|
"PRODUCT INFORMATION WILLIAMS' MEDIUM E ", [ONLINE], シグマ アルドリッチ, 2021年9月21日掲載, 2022, JPN6022049036, ISSN: 0005087049 * |
JOURNAL OF HEPATOLOGY, 2007, VOL.47, PP.253-261, JPN6022049037, ISSN: 0005087047 * |
STEM CELL REPORTS, vol. VOL:4, NR:5, JPN5018003343, 12 May 2015 (2015-05-12), pages 939 - 952, ISSN: 0004926212 * |
STEM CELL REVIEWS AND REPORTS, vol. 7, JPN5018003344, 19 February 2011 (2011-02-19), pages 748 - 759, ISSN: 0005087048 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102022112055A1 (de) | 2021-05-28 | 2022-12-01 | Shimano Inc. | Steuersystem für ein mit menschenkraft angetriebenes fahrzeug |
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