JP6469003B2 - 膵内分泌細胞へのヒト胚性幹細胞の分化 - Google Patents
膵内分泌細胞へのヒト胚性幹細胞の分化 Download PDFInfo
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Description
本出願は、2012年6月8日に出願された、米国特許仮出願第61/657,160号の利益を主張するものであり、その全体が、あらゆる目的について参照により本明細書に組み込まれる。
本発明は、細胞分化の分野にある。より具体的には、本発明は、内分泌細胞への多能性幹細胞の分化の調節因子として、エフリンリガンド及びスフィンゴシン−1−リン酸塩の使用を開示する。
幹細胞は、単一細胞レベルでの自己再生能及び分化能の両方によって定義される未分化細胞である。幹細胞は、自己再生前駆細胞、非再生性前駆細胞、及び最終分化細胞を含む子孫細胞を生成することができる。幹細胞はまた、複数の胚葉(内胚葉、中胚葉及び外胚葉)から様々な細胞系統の機能性細胞へとインビトロで分化する能力を特徴とする。幹細胞は、移植後に複数の胚葉の組織を生じさせ、胚盤胞に注入後、実質的に(全てではないとしても)ほとんどの組織に寄与する。
多能性幹細胞は、段階特異的胚抗原(SSEA)3及び4、並びにTra−1−60及びTra−1−81と呼ばれる抗体を使用して検出可能なマーカーのうちの1つ以上を発現することができる(Thomsonら、1998、Science 282:1145〜1147)。インビトロでの多能性幹細胞の分化は、SSEA−4、Tra−1−60、及びTra−1−81の発現の消失をもたらす。未分化多能性幹細胞は、一般にアルカリホスファターゼ活性を有し、これは、製造業者(米国カリフォルニア州のVector Laboratories)により説明されているように、細胞を4%パラホルムアルデヒドで固定した後、基質としてVector Redを使用して現像することにより検出することができる。未分化の多能性幹細胞はまた、RT−PCRにより検出されるように、一般にOCT4及びTERTも発現する。
使用が可能な多能性幹細胞の種類としては、妊娠期間中の任意の時期(必ずしもではないが、通常は妊娠約10〜12週よりも前)に採取した前胚性組織(例えば胚盤胞など)、胚性組織、又は胎児組織などの、妊娠後に形成される組織に由来する多能性細胞の樹立株が含まれる。非限定的な例は、ヒト胚性幹細胞(hESCs)又はヒト胚生殖細胞の樹立株であり、例えば、ヒト胚性幹細胞株H1、H7、及びH9(米国ウィスコンシン州MadisonのWiCell Research Institute)などである。フィーダー細胞の不在下で既に培養された多能性幹細胞集団から採取した細胞も好適である。また、OCT4、NANOG、Sox2、KLF4、及びZFP42等の多数の多能性に関係する転写因子の強制発現を用いて、成体体細胞から誘導することができる誘導性多能性細胞(IPS)又は再プログラム化された多能性細胞も好適である(Annu Rev Genomics Hum Genet,2011,12:165〜185)。本発明の方法に使用されるヒト胚性幹細胞は、Thomsonらによって記述されたように調製してもよい(米国特許第5,843,780号;Science,1998,282:1145〜1147;Curr Top Dev Biol 1998,38:133〜165;Proc Natl Acad Sci U.S.A.1995,92:7844〜7848)。
多能性幹細胞の特徴は当業者に周知であり、多能性幹細胞の更なる特徴は、継続して同定されている。多能性幹細胞のマーカーとして、例えば、以下のもの、すなわち、ABCG2、cripto、FOXD3、CONNEXIN43、CONNEXIN45、OCT4、SOX2、NANOG、hTERT、UTF1、ZFP42、SSEA−3、SSEA−4、Tra 1−60、Tra 1−81の1つ以上の発現が挙げられる。
インスリン発現の強力な誘発因子としてのエフリンA4の確認
本実施例は、ヒトES細胞の分化から膵内胚葉/内分泌培養の産出に関する多様なタンパクの役割を理解するために実施された。
a)ステージ1(胚体内胚葉(DE)−3日):細胞は、ステージ1培地(0.1%の無脂肪酸BSA(カタログ番号68700,米国アイオワ州アンケニーのProliant)、0.0012g/mLの重炭酸ナトリウム(カタログ番号S3187、米国ミズーリ州セントルイスのSigmaAldrich)、1X GlutaMax(商標)(Invitrogen、カタログ番号35050−079)、4.5mMのD−グルコース(SigmaAldrich、カタログ番号G8769)、100ng/mLのGDF8(米国ミネソタ州ミネアポリスのR&D Systems)及び1μMのMCX化合物(GSK3B阻害剤、14−Prop−2−エン−1−イル−3,5,7,14,17,23,27−へプタアザテトラシクロ[19.3.1.1〜2,6〜.1〜8,12〜]へプタコサ−1(25),2(27),3,5,8(26),9,11,21,23−ノナエン−16−オン、米国特許出願公開第2010−0015711号;参照によりその全体を本明細書に組み入れる)を補充したMCDB−131培地(カタログ番号10372−019、米国カリフォルニア州カールスバッドのInvitrogen)において1日間培養した。次いで、細胞は、0.1%の無脂肪酸BSA、0.0012g/mLの重炭酸ナトリウム、1X GlutaMax(商標)、4.5mMのD−グルコース、100ng/mLのGDF8、及び0.1μMのMCX化合物を補充したMCDB−131倍地でもう1日培養した。次いで、細胞は、0.1%の無脂肪酸BSA、0.0012g/mLの重炭酸ナトリウム、1X GlutaMax(商標)、4.5mMのD−グルコース、及び100ng/mLのGDF8を補充したMCDB−131倍地でもう1日培養し、次いで、
b)ステージ2(前駆腸管−2日):細胞は、0.1%の無脂肪酸BSA、0.0012g/mLの重炭酸ナトリウム、1X GlutaMax(商標)、4.5mMのD−グルコース、0.25mMのアスコルビン酸(米国ミズーリ州セントルイスのSigma)、及び25ng/mLのFGF7(米国ミネソタ州ミネアポリスのR & D Systems)を補充したMCDB−131培地で2日間処理し、次いで、
c)ステージ3(前腸−2日):細胞は、1日目は、ITS−Xの1:200希釈(Invitrogen)、4.5mMのGlucose、1X GlutaMax(商標)、0.0017g/mLの重炭酸ナトリウム、2%の無脂肪酸BSA、0.25μMのSANT−1(米国ミズーリ州セントルイスのSigma)、10ng/mLのアクチビン−A(R & D Systems)、1μMレチノイン酸(RA、Sigma)、25ng/mLのFGF7、0.25mMのアスコルビン酸、200nMのTPB(PKC賦活体;カタログ番号565740;米国ニュージャージー州ギブスタウンのEMD Chemicals)、10μMのフォルスコリン(FSK、Sigma)、及び100nMのLDN(BMP受容体阻害剤;カタログ番号04−0019;米国カリフォルニア州サンディエゴのStemgent)を補充したMCDB−131培地で処理した。2日目、細胞は、ITS−Xの1:200希釈、4.5mMのグルコース、1X GlutaMax(商標)、0.0017g/mLの重炭酸ナトリウム、2%の無脂肪酸BSA、0.25μMのSANT−1、10ng/mLのアクチビンA、1μMのRA、25ng/mLのFGF7、0.25mMのアスコルビン酸、200nMのTPB、10μMのフォルスコリン、及び10nMのLDNを補充したMCDB−131倍地で処理し、次いで、
d)ステージ4(膵臓前腸前駆細胞−2日):細胞は、ITS−Xの1:200希釈、4.5mMのグルコース、1X GlutaMax(商標)、0.0015g/mLの重炭酸ナトリウム、2%の無脂肪酸BSA、0.25μMのSANT−1、50nMのRA、50μMのLDN−193189、10μMのフォルスコリン、0.25mMのアスコルビン酸、及び100nMのTPBを補充したMCDB−131倍地で2日間処理し、次いで、
e)ステージ5(膵内胚葉/内分泌−3日):ステージ4細胞は、ITS−Xの1:200希釈、20mMのグルコース、1X GlutaMax(商標)、0.0015g/mLの重炭酸ナトリウム、2%の無脂肪酸BSA、0.25μMのSANT−1、50nMのRA、10μMのフォルスコリン、0.25mMのアスコルビン酸を補充し、2〜3日目のみ、100nMのALk5阻害剤SD−208(Molecular Pharmacology 2007,72:152〜161に開示される)を添加したMCDB−131培地で3日間処理した。
S5でのインスリン発現に関するエフリンの影響の検証
この実施例は、実施例1において特定された該当点の検定を説明する。具体的には、プロトコルのS5でのエフリン−A3又はエフリン−A4の添加の影響を以下に列挙する。
a)ステージ1(胚体内胚葉(DE)−3日):細胞は、ステージ1の培地(上記の実施例1を参照)で1日間培養した。次いで、細胞は、0.1%の無脂肪酸BSA、0.0012g/mLの重炭酸ナトリウム、1X GlutaMax(商標)、4.5mMのD−グルコース、100ng/mLのGDF8、及び0.1μMのMCX化合物を補充したMCDB−131倍地でもう1日培養した。次いで、細胞は、0.1%の無脂肪酸BSA、0.0012g/mLの重炭酸ナトリウム、1X GlutaMax(商標)、4.5mMのD−グルコース、及び100ng/mLのGDF8を補充したMCDB−131倍地でもう1日培養し、次いで、
b)ステージ2(前駆腸管−2日):細胞は、0.1%の無脂肪酸BSA、0.0012g/mLの重炭酸ナトリウム、1X GlutaMax(商標)、4.5mMのD−グルコース、0.25mMのアスコルビン酸(米国ミズーリ州のSigma)、及び25ng/mLのFGF7(米国ミネソタ州のR & D Systems)を補充したMCDB−131培地で2日間処理し、次いで、
c)ステージ3(前腸−2日):細胞は、1日目、1:200希釈のITS−X(米国カリフォルニア州のInvitrogen)、4.5mMのグルコース、1X GlutaMax(商標)、0.0017g/mLの重炭酸ナトリウム、2%の無脂肪酸BSA、0.25μMのSANT−1(米国ミズーリ州のSigma)、10ng/mLのアクチビン−A(米国ミネソタ州のR & D Systems)、1μMのレチノイン酸(米国ミズーリ州のSigma)、25ng/mLのFGF7、0.25mMのアスコルビン酸、200nMのTPB(PKC賦活体、カタログ番号565740、米国ニュージャージー州ギブスタウンのEMD Chemicals)、10μMのフォルスコリン、及び100nMのLDN(BMP受容体阻害剤、カタログ番号04−0019、Stemgent)を補充したMCDB−131培地で処理した。2日目、細胞は、ITS−Xの1:200希釈、4.5mMのグルコース、1X GlutaMax(商標)、0.0017g/mLの重炭酸ナトリウム、2%の無脂肪酸BSA、0.25μMのSANT−1、10ng/mLのアクチビン−A、1μMのRA、25ng/mLのFGF7、0.25mMのアスコルビン酸、200nMのTPB、10μMのフォルスコリン、及び10nMのLDNを補充したMCDB−131倍地で処理し、次いで、
d)ステージ4(膵臓前腸前駆細胞−2日):細胞は、ITS−Xの1:200希釈、4.5mMのグルコース、1X GlutaMax(商標)、0.0015g/mLの重炭酸ナトリウム、2%の無脂肪酸BSA、0.25μMのSANT−1、50nMのRA、50μMのLDN−193189、10μMのフォルスコリン、0.25mMのアスコルビン酸、及び100nMのTPBを補充したMCDB−131倍地で2日間処理し、次いで、
e)ステージ5(膵内胚葉/内分泌−3日):ステージ4細胞は、ITS−Xの1:200希釈;4.5mMグルコース、1X GlutaMax(商標)、0.0015g/mLの重炭酸ナトリウム、2%の無脂肪酸BSA、0.25μMのSANT−1、50nMのRA、10μMのフォルスコリン、0.25mMのアスコルビン酸、100nMのALk5阻害剤(2〜3日目のみ)(SD−208、Molecular Pharmacology 2007,72:152〜161に開示)、及び+/−0〜100ng/mLのエフリン−A3又はエフリン−A4(米国ミネソタ州のR & D systems)を補充したMCDB−131培地で3日間処理した。
S6でのスフィンゴシン−1−リン酸塩の添加は、内分泌ホルモンを含む細胞クラスター形成を大幅に加速
この実施例では、ステージ6での内分泌腺クラスター形成の進行、及び内分泌腺リッチクラスターの形成の加速化におけるスフィンゴシン−1−リン酸塩の影響を説明する。
a)ステージ1(胚体内胚葉(DE)−3日):細胞は、ステージ1の培地(上記の実施例1を参照)で1日間培養された。次いで、細胞は、0.1%の無脂肪酸BSA、0.0012g/mLの重炭酸ナトリウム、1X GlutaMax(商標)、4.5mMのD−グルコース、100ng/mLのGDF8、及び0.1μMのMCX化合物を補充したMCDB−131倍地でもう1日培養した。次いで、細胞は、0.1%の無脂肪酸BSA、0.0012g/mLの重炭酸ナトリウム、1X GlutaMax(商標)、4.5mMのD−グルコース、及び100ng/mLのGDF8を補充したMCDB−131倍地でもう1日培養し、次いで、
b)ステージ2(前駆腸管−2日):細胞は、0.1%の無脂肪酸BSA、0.0012g/mLの重炭酸ナトリウム、1X GlutaMax(商標)、4.5mMのD−グルコース、0.25mMのアスコルビン酸(米国ミズーリ州のSigma)及び25ng/mLのFGF7(米国ミネソタ州のR & D Systems)を補充したMCDB−131培地で2日間処理し、次いで、
c)ステージ3(前腸−2日):細胞は、1日目、ITS−Xの1:200希釈(米国カリフォルニア州のInvitrogen)、4.5mMのグルコース、1X GlutaMax(商標)、0.0017g/mLの重炭酸ナトリウム、2%の無脂肪酸BSA、0.25μMのSANT−1(米国ミズーリ州のSigma)、10ng/mLのアクチビン−A(米国ミネソタ州のR & D Systems)、1μMのレチノイン酸(米国ミズーリ州のSigma)、25ng/mLのFGF7、0.25mMのアスコルビン酸、200nMのTPB(PKC賦活体、カタログ番号565740、米国ニュージャージー州ギブスタウンのEMD Chemicals)、10μMのフォルスコリン(FSK、米国ミズーリ州のSigma)、及び100nMのLDN(BMP受容体阻害剤、カタログ番号04−0019、米国カリフォルニア州のStemgent)を補充したMCDB−131培地で処理した。2日目、細胞は、ITS−Xの1:200希釈、4.5mMのグルコース、1X GlutaMax(商標)、0.0017g/mLの重炭酸ナトリウム、2%の無脂肪酸BSA、0.25μMのSANT−1、10ng/mLのアクチビン−A、1μMのRA、25ng/mLのFGF7、0.25mMのアスコルビン酸、200nMのTPB、及び10nMのLDNを補充したMCDB−131倍地で処理し、次いで、
d)ステージ4(膵臓前腸前駆細胞−2日):細胞は、ITS−Xの1:200希釈、4.5mMのグルコース、1X GlutaMax(商標)、0.0015g/mLの重炭酸ナトリウム、2%の無脂肪酸BSA、0.25μMのSANT−1、50nMのRA、50μMのLDN−193189、10μMのフォルスコリン、0.25mMのアスコルビン酸、2ng/mLのFGF7、1ng/mLのAA、及び100nMのTPBを補充したMCDB−131倍地で2日間処理し、次いで、
e)ステージ5(膵内胚葉/内分泌−3日):ステージ4細胞は、ITS−Xの1:200希釈、15mMのグルコース、1X GlutaMax(商標)、0.0015g/mLの重炭酸ナトリウム、2%の無脂肪酸BSA、0.25μMのSANT−1、50nMのRA、10μMのフォルスコリン、0.25mMのアスコルビン酸、及び1ng/mLのFGF7、2〜3日目のみ100nMのALK5阻害剤SD208を添加して補充したMCDB−131培地で3日間処理し、次いで、
f)ステージ6(膵内胚葉−3〜10日):ステージ5細胞を、ITS−Xの1:200希釈、15mMのグルコース、1X GlutaMax(商標)、0.0015g/mLの重炭酸ナトリウム、2%の無脂肪酸BSA、0.25μMのSANT−1、50nMのRA、0.25mMのアスコルビン酸を補充したMCDB−131倍地で3〜10日間処理した。一部の培養物は、10μMのスフィンゴシン−1−リン酸塩(米国ミズーリ州のSigma)を3日間添加した。
て免疫染色した細胞(図6D)を表す。S1Pで処理した培養において、内分泌クラスタ
ーでは、NKX2.2+細胞が培養全体で均一に分布された対照培養(図6D)と比較し
て、NKX2.2+細胞でも濃縮(図6C)した。
上記の開示によって提供される発明の例として、以下のものが挙げられる。
[1] エフリンリガンドを用いて膵内胚葉細胞を培養することを含む、ホルモン発現細胞におけるインスリン発現を誘発する方法。
[2] 前記エフリンリガンドを用いて前記膵内胚葉細胞を培養することが、NKX6.1の発現も強化する、[2]に記載の方法。
[3] エフリンリガンドを用いて前記膵内胚葉細胞を培養することが、非処理の膵臓内胚葉細胞におけるインスリン及びNKX6.1の発現と比較して、前記膵内胚葉細胞におけるインスリン及びNKX6.1の発現を強化する、[2]に記載の方法。
[4] 前記膵内胚葉細胞が、CDX2又はSOX2を実質的に発現しない[3]に記載の方法。
[5] 前記膵内胚葉細胞が、ほぼ約10%未満のCDX2又はSOX2を発現する、[4]に記載の方法。
[6] 前記エフリンリガンドが、エフリンA3又はエフリンA4である、[1]〜[5]のいずれか1項に記載の方法。
[7] 前記膵内胚葉細胞が、多能性幹細胞の段階的分化によって取得される、[6]に記載の方法。
[8] 前記多能性幹細胞が、ヒト胚性多能性幹細胞である、[7]に記載の方法。
[9] 請求項1の方法によって調製されたインスリン及びNKX6.1発現細胞。
[10] エフリンリガンドを用いて膵内胚葉細胞を培養することによって調製された細胞集団であって、前記細胞集団が、エフリンリガンドで処理していない膵内胚葉細胞と比較して、強化されたインスリン及びNKX6.1を発現する、細胞集団。
[11] 前記エフリンリガンドが、エフリンA3又はエフリンA4である、[10]に記載の細胞集団。
[12] アクチビンA又はアクチビンCを含む培地において膵臓内胚葉細胞を培養することを含む、ホルモン発現細胞における成長ホルモン分泌抑制ホルモンの発現を増強する方法。
[13] インスリン、グルカゴン、及びグレリンの発現が抑制される、[12]に記載の方法。
[14] アクチビンA又はアクチビンCで処理した前記膵内胚葉細胞集団が、アクチビンA又はアクチビンCで処理していない膵内胚葉細胞集団より多くの成長ホルモン分泌抑制ホルモンを発現する、[12]に記載の方法。
[15] インスリンの前記発現が、アクチビンA又はアクチビンCで処理した前記膵内胚葉細胞集団において、アクチビンA又はアクチビンCで処理していない膵内胚葉細胞集団におけるインスリンの前記発現と比較して抑制される、[14]に記載の方法。
[16] グルカゴンの前記発現が、アクチビンA又はアクチビンCで処理した前記膵内胚葉細胞集団において、アクチビンA又はアクチビンCで処理していない膵内胚葉細胞集団におけるグルカゴンの前記発現と比較して抑制される、[12]に記載の方法。
[17] グレリンの前記発現が、アクチビンA又はアクチビンCで処理した前記膵内胚葉細胞集団において、アクチビンA又はアクチビンCで処理していない膵内胚葉細胞集団におけるグレリンの前記発現と比較して抑制される、[12]に記載の方法。
[18] 前記膵内胚葉細胞が、CDX2又はSOX2を実質的に発現しない、[12]〜[18]のいずれか1項に記載の方法。
[19] アクチビンA又はアクチビンCで処理された前記膵内胚葉細胞が、多能性細胞の段階的分化によって取得される、[18]に記載の方法。
[20] 前記膵内胚葉細胞の由来元である前記多能性細胞が、ヒト胚性多能性細胞である、[19]に記載の方法。
[21] セマフォリン3a又はエピゲンを含む培地において膵内胚葉細胞を処理することによって、NKX6.1の発現を増強する方法。
[22] セマフォリン3a又はエピゲンを含む培地で処理した前記膵内胚葉細胞集団が、セマフォリン3a又はエピゲンを含む培地で処理されていない膵内胚葉細胞に比較して強化された量のNKX6.1を発現する、[21]に記載の方法。
[23] インスリン、グルカゴン、及びグレリンの発現レベルが、セマフォリン3a又はエピゲンを含む培地で処理した膵内胚葉細胞において、セマフォリン3a又はエピゲンを含む培地で処理していない膵内胚葉細胞に比較して影響を受けない、[21]に記載の方法。
[24] スフィンゴシン−1受容体アゴニストを用いて膵内分泌細胞を培養することを含む、内分泌クラスターの形成を誘導するための方法。
[25] 膵内分泌細胞を処理するために使用された前記スフィンゴシン−1受容体アゴニストが、スフィンゴシン−1−リン酸塩(S1P)である、[24]に記載の方法。
[26] 前記膵内分泌細胞が、多能性幹細胞の段階的分化によって取得される、[24]に記載の方法。
[27] 前記多能性幹細胞が、ヒト胚性多能性幹細胞である、[26]に記載の方法。
Claims (9)
- エフリンリガンドを用いて膵内胚葉細胞を培養することを含む、ホルモン発現細胞におけるインスリン発現を誘発する方法であって、前記エフリンリガンドがエフリンA3またはエフリンA4である、方法。
- 前記エフリンリガンドがエフリンA3である、請求項1に記載の方法。
- 前記エフリンリガンドがエフリンA4である、請求項1に記載の方法。
- 前記エフリンリガンドを用いて前記膵内胚葉細胞を培養することが、NKX6.1の発現も強化する、請求項3に記載の方法。
- 前記膵内胚葉細胞が、CDX2又はSOX2を発現しない、請求項4に記載の方法。
- 前記膵内胚葉細胞が、10%未満のCDX2又はSOX2を発現する、請求項4に記載の方法。
- 前記膵内胚葉細胞が、多能性幹細胞の段階的分化によって取得される、請求項1〜6のいずれか1項に記載の方法。
- 前記多能性幹細胞がヒト多能性幹細胞である、請求項7に記載の方法。
- 前記多能性幹細胞が、ヒト胚性多能性幹細胞である、請求項7に記載の方法。
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EP2859091B1 (en) | 2012-06-08 | 2018-08-29 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells into pancreatic endocrine cells |
MX2015008619A (es) | 2012-12-31 | 2016-01-12 | Janssen Biotech Inc | Suspension y agrupamiento de celulas humanas pluripotentes para la diferenciacion a celulas endocrinas pancreaticas. |
RU2684215C2 (ru) | 2012-12-31 | 2019-04-04 | Янссен Байотек, Инк. | Способ получения панкреатических эндокринных клеток (варианты) и способ увеличения выхода бета-клеток |
WO2014105543A1 (en) * | 2012-12-31 | 2014-07-03 | Janssen Biotech, Inc. | Culturing of human embryonic stem cells at the air-liquid interface for differentiation into pancreatic endocrine cells |
US10370644B2 (en) | 2012-12-31 | 2019-08-06 | Janssen Biotech, Inc. | Method for making human pluripotent suspension cultures and cells derived therefrom |
US8859286B2 (en) | 2013-03-14 | 2014-10-14 | Viacyte, Inc. | In vitro differentiation of pluripotent stem cells to pancreatic endoderm cells (PEC) and endocrine cells |
DE202014011287U1 (de) | 2013-06-11 | 2019-02-06 | The President And Fellows Of Harvard College | SC-ß Zellen und Zusammensetzungen zur Erzeugung der Zellen |
JP6588969B2 (ja) | 2014-05-16 | 2019-10-09 | ヤンセン バイオテツク,インコーポレーテツド | 膵内分泌細胞内のmafa発現を強化するための小分子の使用 |
EP3147353B1 (en) * | 2014-05-21 | 2022-03-30 | Kyoto University | Method for producing pancreatic blast cells and pancreatic disease treatment agent containing pancreatic blast cells |
CN107614678B (zh) | 2014-12-18 | 2021-04-30 | 哈佛学院校长同事会 | 干细胞来源的β细胞的产生方法及其使用方法 |
WO2016100898A1 (en) | 2014-12-18 | 2016-06-23 | President And Fellows Of Harvard College | Serum-free in vitro directed differentiation protocol for generating stem cell-derived b cells and uses thereof |
EP3234110B1 (en) | 2014-12-18 | 2024-02-28 | President and Fellows of Harvard College | METHODS FOR GENERATING STEM CELL-DERIVED ß CELLS AND USES THEREOF |
US20190169574A1 (en) * | 2016-02-04 | 2019-06-06 | Nestec S.A. | In vitro production of pancreatic beta cells |
MA45479A (fr) | 2016-04-14 | 2019-02-20 | Janssen Biotech Inc | Différenciation de cellules souches pluripotentes en cellules de l'endoderme de l'intestin moyen |
MA45502A (fr) * | 2016-06-21 | 2019-04-24 | Janssen Biotech Inc | Génération de cellules bêta fonctionnelles dérivées de cellules souches pluripotentes humaines ayant une respiration mitochondriale glucose-dépendante et une réponse en sécrétion d'insuline en deux phases |
EP3638774A1 (en) * | 2017-06-14 | 2020-04-22 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Methods for purifying endoderm and pancreatic endoderm cells derived from human embryonic stem cells |
US10391156B2 (en) | 2017-07-12 | 2019-08-27 | Viacyte, Inc. | University donor cells and related methods |
AU2018370029A1 (en) | 2017-11-15 | 2020-07-02 | Vertex Pharmaceuticals Incorporated | Islet cell manufacturing compositions and methods of use |
WO2019222487A1 (en) * | 2018-05-16 | 2019-11-21 | Washington University | Methods and compositions for generating cells of endodermal lineage and beta cells and uses thereof |
WO2020033879A1 (en) | 2018-08-10 | 2020-02-13 | Semma Therapeutics, Inc. | Stem cell derived islet differentiation |
CN111848744B (zh) * | 2018-09-03 | 2021-07-23 | 宁波希诺赛生物科技有限公司 | 表皮干细胞向胰腺细胞分化的改进方法 |
US10724052B2 (en) | 2018-09-07 | 2020-07-28 | Crispr Therapeutics Ag | Universal donor cells |
US11014897B1 (en) | 2018-10-16 | 2021-05-25 | Celgene Corporation | Solid forms comprising a thiazolidinone compound, compositions and methods of use thereof |
US11014940B1 (en) | 2018-10-16 | 2021-05-25 | Celgene Corporation | Thiazolidinone and oxazolidinone compounds and formulations |
US11013723B1 (en) | 2018-10-16 | 2021-05-25 | Celgene Corporation | Solid forms of a thiazolidinone compound, compositions and methods of use thereof |
US11186556B1 (en) | 2018-10-16 | 2021-11-30 | Celgene Corporation | Salts of a thiazolidinone compound, solid forms, compositions and methods of use thereof |
EP3976237A1 (en) | 2019-05-31 | 2022-04-06 | W.L. Gore & Associates Inc. | Cell encapsulation devices with controlled oxygen diffusion distances |
WO2020243665A1 (en) | 2019-05-31 | 2020-12-03 | W. L. Gore & Associates, Inc. | A biocompatible membrane composite |
EP3976236A1 (en) | 2019-05-31 | 2022-04-06 | W.L. Gore & Associates Inc. | A biocompatible membrane composite |
EP3975926A1 (en) | 2019-05-31 | 2022-04-06 | W.L. Gore & Associates, Inc. | A biocompatible membrane composite |
CA3150235A1 (en) | 2019-09-05 | 2021-03-11 | Alireza Rezania | UNIVERSAL DONOR CELLS |
CN114364791A (zh) | 2019-09-05 | 2022-04-15 | 克里斯珀医疗股份公司 | 通用供体细胞 |
CA3158631A1 (en) * | 2019-10-21 | 2021-04-29 | Orizuru Therapeutics, Inc. | Growth inhibitor |
EP4271796A1 (en) | 2020-12-31 | 2023-11-08 | CRISPR Therapeutics AG | Universal donor cells |
CN114634904B (zh) * | 2022-05-17 | 2022-09-13 | 天津外泌体科技有限公司 | 高纯度胰腺祖细胞的产生方法 |
Family Cites Families (272)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3209652A (en) | 1961-03-30 | 1965-10-05 | Burgsmueller Karl | Thread whirling method |
AT326803B (de) | 1968-08-26 | 1975-12-29 | Binder Fa G | Maschenware sowie verfahren zur herstellung derselben |
US3935067A (en) | 1974-11-22 | 1976-01-27 | Wyo-Ben Products, Inc. | Inorganic support for culture media |
CA1201400A (en) | 1982-04-16 | 1986-03-04 | Joel L. Williams | Chemically specific surfaces for influencing cell activity during culture |
US4499802A (en) | 1982-09-29 | 1985-02-19 | Container Graphics Corporation | Rotary cutting die with scrap ejection |
US4537773A (en) | 1983-12-05 | 1985-08-27 | E. I. Du Pont De Nemours And Company | α-Aminoboronic acid derivatives |
US4557264A (en) | 1984-04-09 | 1985-12-10 | Ethicon Inc. | Surgical filament from polypropylene blended with polyethylene |
US5089396A (en) | 1985-10-03 | 1992-02-18 | Genentech, Inc. | Nucleic acid encoding β chain prodomains of inhibin and method for synthesizing polypeptides using such nucleic acid |
US5215893A (en) | 1985-10-03 | 1993-06-01 | Genentech, Inc. | Nucleic acid encoding the ba chain prodomains of inhibin and method for synthesizing polypeptides using such nucleic acid |
US4737578A (en) | 1986-02-10 | 1988-04-12 | The Salk Institute For Biological Studies | Human inhibin |
US5863531A (en) | 1986-04-18 | 1999-01-26 | Advanced Tissue Sciences, Inc. | In vitro preparation of tubular tissue structures by stromal cell culture on a three-dimensional framework |
US5567612A (en) | 1986-11-20 | 1996-10-22 | Massachusetts Institute Of Technology | Genitourinary cell-matrix structure for implantation into a human and a method of making |
CA1340581C (en) | 1986-11-20 | 1999-06-08 | Joseph P. Vacanti | Chimeric neomorphogenesis of organs by controlled cellular implantation using artificial matrices |
US5759830A (en) | 1986-11-20 | 1998-06-02 | Massachusetts Institute Of Technology | Three-dimensional fibrous scaffold containing attached cells for producing vascularized tissue in vivo |
NZ229354A (en) | 1988-07-01 | 1990-09-26 | Becton Dickinson Co | Treating polymer surfaces with a gas plasma and then applying a layer of endothelial cells to the surface |
EP0363125A3 (en) | 1988-10-03 | 1990-08-16 | Hana Biologics Inc. | Proliferated pancreatic endocrine cell product and process |
SU1767433A1 (ru) | 1989-11-27 | 1992-10-07 | Пермский государственный медицинский институт | Способ определени инсулинорезистентности имунного генеза у больных сахарным диабетом I типа |
US5837539A (en) | 1990-11-16 | 1998-11-17 | Osiris Therapeutics, Inc. | Monoclonal antibodies for human mesenchymal stem cells |
KR100249937B1 (ko) | 1991-04-25 | 2000-04-01 | 나가야마 오사무 | 인간 인터루킨-6 수용체에 대한 재구성 인간 항체 |
US5449383A (en) | 1992-03-18 | 1995-09-12 | Chatelier; Ronald C. | Cell growth substrates |
GB9206861D0 (en) | 1992-03-28 | 1992-05-13 | Univ Manchester | Wound healing and treatment of fibrotic disorders |
CA2114282A1 (en) | 1993-01-28 | 1994-07-29 | Lothar Schilder | Multi-layered implant |
JP3525221B2 (ja) | 1993-02-17 | 2004-05-10 | 味の素株式会社 | 免疫抑制剤 |
WO1994023572A1 (en) | 1993-04-08 | 1994-10-27 | Human Cell Cultures, Inc. | Cell culturing method and medium |
US5523226A (en) | 1993-05-14 | 1996-06-04 | Biotechnology Research And Development Corp. | Transgenic swine compositions and methods |
GB9310557D0 (en) | 1993-05-21 | 1993-07-07 | Smithkline Beecham Plc | Novel process and apparatus |
TW257671B (ja) | 1993-11-19 | 1995-09-21 | Ciba Geigy | |
US6703017B1 (en) | 1994-04-28 | 2004-03-09 | Ixion Biotechnology, Inc. | Reversal of insulin-dependent diabetes by islet-producing stem cells, islet progenitor cells and islet-like structures |
US6001647A (en) | 1994-04-28 | 1999-12-14 | Ixion Biotechnology, Inc. | In vitro growth of functional islets of Langerhans and in vivo uses thereof |
US5834308A (en) | 1994-04-28 | 1998-11-10 | University Of Florida Research Foundation, Inc. | In vitro growth of functional islets of Langerhans |
US6083903A (en) | 1994-10-28 | 2000-07-04 | Leukosite, Inc. | Boronic ester and acid compounds, synthesis and uses |
WO1996020728A1 (fr) | 1994-12-29 | 1996-07-11 | Chugai Seiyaku Kabushiki Kaisha | Potentialisateur d'agent antitumoral comprenant un antagoniste de l'interleukine 6 |
US5843780A (en) | 1995-01-20 | 1998-12-01 | Wisconsin Alumni Research Foundation | Primate embryonic stem cells |
US5718922A (en) | 1995-05-31 | 1998-02-17 | Schepens Eye Research Institute, Inc. | Intravitreal microsphere drug delivery and method of preparation |
US5908782A (en) | 1995-06-05 | 1999-06-01 | Osiris Therapeutics, Inc. | Chemically defined medium for human mesenchymal stem cells |
US5681561A (en) | 1995-06-07 | 1997-10-28 | Life Medical Sciences, Inc. | Compositions and methods for improving autologous fat grafting |
WO1998030679A1 (en) | 1997-01-10 | 1998-07-16 | Life Technologies, Inc. | Embryonic stem cell serum replacement |
KR100568438B1 (ko) | 1997-04-24 | 2006-04-07 | 오르토-맥네일 파마슈티칼, 인코퍼레이티드 | 염증성 질환의 치료에 유용한 치환된 이미다졸, 이의 제조방법 및 이를 포함하는 약제학적 조성물 |
AU8476698A (en) | 1997-07-03 | 1999-01-25 | Osiris Therapeutics, Inc. | Human mesenchymal stem cells from peripheral blood |
EP1538206B1 (en) | 1997-09-16 | 2010-03-24 | Centocor, Inc. | Method for the complete chemical synthesis and assembly of genes and genomes |
US6670127B2 (en) | 1997-09-16 | 2003-12-30 | Egea Biosciences, Inc. | Method for assembly of a polynucleotide encoding a target polypeptide |
AU1197699A (en) | 1997-10-23 | 1999-05-10 | Geron Corporation | Methods and materials for the growth of primate-derived primordial stem cells |
US6372779B1 (en) | 1997-12-29 | 2002-04-16 | Ortho Pharmaceutical Corporation | Anti-inflammatory compounds |
ATE316795T1 (de) | 1998-03-18 | 2006-02-15 | Osiris Therapeutics Inc | Mesenchymale stammzellen für die prävention und behandlung von immunantworten bei transplantationen |
MY132496A (en) | 1998-05-11 | 2007-10-31 | Vertex Pharma | Inhibitors of p38 |
US6413773B1 (en) | 1998-06-01 | 2002-07-02 | The Regents Of The University Of California | Phosphatidylinositol 3-kinase inhibitors as stimulators of endocrine differentiation |
US6667176B1 (en) | 2000-01-11 | 2003-12-23 | Geron Corporation | cDNA libraries reflecting gene expression during growth and differentiation of human pluripotent stem cells |
US7410798B2 (en) | 2001-01-10 | 2008-08-12 | Geron Corporation | Culture system for rapid expansion of human embryonic stem cells |
US6610540B1 (en) | 1998-11-18 | 2003-08-26 | California Institute Of Technology | Low oxygen culturing of central nervous system progenitor cells |
US6413556B1 (en) | 1999-01-08 | 2002-07-02 | Sky High, Llc | Aqueous anti-apoptotic compositions |
CA2359159A1 (en) | 1999-01-21 | 2000-07-27 | Vitro Diagnostics, Inc. | Immortalized cell lines and methods of making the same |
US6815203B1 (en) | 1999-06-23 | 2004-11-09 | Joslin Diabetes Center, Inc. | Methods of making pancreatic islet cells |
US6306424B1 (en) | 1999-06-30 | 2001-10-23 | Ethicon, Inc. | Foam composite for the repair or regeneration of tissue |
US6333029B1 (en) | 1999-06-30 | 2001-12-25 | Ethicon, Inc. | Porous tissue scaffoldings for the repair of regeneration of tissue |
WO2001023528A1 (en) | 1999-09-27 | 2001-04-05 | University Of Florida Research Foundation | Reversal of insulin-dependent diabetes by islet-producing stem cells, islet progenitor cells and islet-like structures |
US6685936B2 (en) | 1999-10-12 | 2004-02-03 | Osiris Therapeutics, Inc. | Suppressor cells induced by culture with mesenchymal stem cells for treatment of immune responses in transplantation |
US20030082155A1 (en) | 1999-12-06 | 2003-05-01 | Habener Joel F. | Stem cells of the islets of langerhans and their use in treating diabetes mellitus |
US6753153B2 (en) | 1999-12-13 | 2004-06-22 | The Scripps Research Institute | Markers for identification and isolation of pancreatic islet α and β progenitors |
US7439064B2 (en) | 2000-03-09 | 2008-10-21 | Wicell Research Institute, Inc. | Cultivation of human embryonic stem cells in the absence of feeder cells or without conditioned medium |
US7005252B1 (en) | 2000-03-09 | 2006-02-28 | Wisconsin Alumni Research Foundation | Serum free cultivation of primate embryonic stem cells |
US6436704B1 (en) | 2000-04-10 | 2002-08-20 | Raven Biotechnologies, Inc. | Human pancreatic epithelial progenitor cells and methods of isolation and use thereof |
US6458589B1 (en) | 2000-04-27 | 2002-10-01 | Geron Corporation | Hepatocyte lineage cells derived from pluripotent stem cells |
CN1449439A (zh) | 2000-06-26 | 2003-10-15 | 株式会社雷诺再生医学研究所 | 细胞级分包括能分化为神经细胞的细胞 |
KR100850812B1 (ko) | 2000-10-23 | 2008-08-06 | 스미스클라인 비참 코포레이션 | 신규 화합물 |
DK1362047T3 (da) | 2000-12-08 | 2006-09-04 | Ortho Mcneil Pharm Inc | Indazolylsubstituerede pyrrolinforbindelser som kinaseinhibitorer |
JP2004526676A (ja) | 2000-12-08 | 2004-09-02 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | キナーゼ阻害剤として有用な大員複素環式化合物 |
US6599323B2 (en) | 2000-12-21 | 2003-07-29 | Ethicon, Inc. | Reinforced tissue implants and methods of manufacture and use |
JP2005503759A (ja) | 2001-01-24 | 2005-02-10 | アメリカ合衆国 | 幹細胞の膵臓内分泌細胞への分化方法 |
DK1355910T3 (da) | 2001-01-25 | 2011-06-27 | Us Of America Represented By The Secretary Dept Of Health And Human Services | Formulering af borsyreforbindelser |
US6656488B2 (en) | 2001-04-11 | 2003-12-02 | Ethicon Endo-Surgery, Inc. | Bioabsorbable bag containing bioabsorbable materials of different bioabsorption rates for tissue engineering |
EP1379626A2 (en) | 2001-04-19 | 2004-01-14 | DeveloGen Aktiengesellschaft für entwicklungsbiologische Forschung | A method for differentiating stem cells into insulin-producing cells |
JP4296781B2 (ja) | 2001-04-24 | 2009-07-15 | 味の素株式会社 | 幹細胞及びその分離方法 |
CA2447015A1 (en) | 2001-05-15 | 2002-11-21 | Rappaport Family Institute For Research In The Medical Sciences | Insulin producing cells derived from human embryonic stem cells |
US6626950B2 (en) | 2001-06-28 | 2003-09-30 | Ethicon, Inc. | Composite scaffold with post anchor for the repair and regeneration of tissue |
KR100418195B1 (ko) | 2001-07-05 | 2004-02-11 | 주식회사 우리기술 | 전력케이블의 다중절연진단장치 및 그 방법 |
GB0117583D0 (en) | 2001-07-19 | 2001-09-12 | Astrazeneca Ab | Novel compounds |
WO2003014313A2 (en) | 2001-08-06 | 2003-02-20 | Bresagen, Ltd. | Alternative compositions and methods for the culture of stem cells |
US6617152B2 (en) | 2001-09-04 | 2003-09-09 | Corning Inc | Method for creating a cell growth surface on a polymeric substrate |
EP1298201A1 (en) | 2001-09-27 | 2003-04-02 | Cardion AG | Process for the production of cells exhibiting an islet-beta-cell-like state |
WO2003033697A1 (en) | 2001-10-18 | 2003-04-24 | Ixion Biotechnology, Inc. | Conversion of liver stem and progenitor cells to pancreatic functional cells |
EP1442115B9 (en) | 2001-11-15 | 2009-12-16 | Children's Medical Center Corporation | Methods of isolation, expansion and differentiation of fetal stem cells from chorionic villus, amniotic fluid, and placenta and therapeutic uses thereof |
KR20120003961A (ko) | 2001-12-07 | 2012-01-11 | 사이토리 테라퓨틱스, 인크. | 처리된 리포애스퍼레이트 세포로 환자를 치료하기 위한 시스템 및 방법 |
EP2264146A1 (en) | 2001-12-07 | 2010-12-22 | Geron Corporation | Islet cells from human embryonic stem cells |
AU2002218893A1 (en) | 2001-12-21 | 2003-07-09 | Thromb-X Nv | Compositions for the in vitro derivation and culture of embryonic stem (es) cell lines with germline transmission capability |
JP2005512593A (ja) | 2001-12-28 | 2005-05-12 | セルアーティス アーベー | 多能性のヒト胚盤胞由来幹細胞株の樹立方法 |
US20030162290A1 (en) | 2002-01-25 | 2003-08-28 | Kazutomo Inoue | Method for inducing differentiation of embryonic stem cells into functioning cells |
US20030180268A1 (en) | 2002-02-05 | 2003-09-25 | Anthony Atala | Tissue engineered construct for supplementing or replacing a damaged organ |
GB0207440D0 (en) * | 2002-03-28 | 2002-05-08 | Ppl Therapeutics Scotland Ltd | Tolerogenic antigen-presenting cells |
JPWO2003087349A1 (ja) | 2002-04-17 | 2005-08-18 | 大塚製薬株式会社 | 間葉系細胞から膵β細胞を形成する方法 |
US20040161419A1 (en) | 2002-04-19 | 2004-08-19 | Strom Stephen C. | Placental stem cells and uses thereof |
DE60319364T2 (de) | 2002-05-08 | 2009-02-19 | Janssen Pharmaceutica N.V. | Substituierte pyrroline als kinase inhibitoren |
US20060003446A1 (en) | 2002-05-17 | 2006-01-05 | Gordon Keller | Mesoderm and definitive endoderm cell populations |
JP2006512046A (ja) | 2002-05-28 | 2006-04-13 | ベクトン・ディキンソン・アンド・カンパニー | invitroにおけるヒト膵臓腺房細胞の増殖およびインスリン産生細胞への分化転換のための方法 |
BR0311821A (pt) | 2002-06-05 | 2005-04-05 | Janssen Pharmaceutica Nv | Derivados de bisindolil-maleimid como inibidores de cinase |
GB0212976D0 (en) | 2002-06-06 | 2002-07-17 | Tonejet Corp Pty Ltd | Ejection method and apparatus |
CN1171991C (zh) | 2002-07-08 | 2004-10-20 | 徐如祥 | 人神经干细胞的培养方法 |
US6877147B2 (en) | 2002-07-22 | 2005-04-05 | Broadcom Corporation | Technique to assess timing delay by use of layout quality analyzer comparison |
US7838290B2 (en) | 2002-07-25 | 2010-11-23 | The Scripps Research Institute | Hematopoietic stem cells and methods of treatment of neovascular eye diseases therewith |
EP1539930A4 (en) | 2002-07-29 | 2006-08-09 | Es Cell Int Pte Ltd | METHOD IN MULTIPLE STAGES OF DIFFERENTIATION OF POSITIVE INSULIN-SENSITIVE CELLS, GLUCOSE |
US20040063204A1 (en) | 2002-08-14 | 2004-04-01 | Lijun Yang | Bone marrow cell differentiation |
EP1539928A4 (en) | 2002-09-06 | 2006-09-06 | Amcyte Inc | POSIOTIVE PANCREATIC ENDOCRINE PROGENITOR CELLS CD56 IN ADULT HUMAN BEINGS |
US9969977B2 (en) | 2002-09-20 | 2018-05-15 | Garnet Biotherapeutics | Cell populations which co-express CD49c and CD90 |
US20040062753A1 (en) | 2002-09-27 | 2004-04-01 | Alireza Rezania | Composite scaffolds seeded with mammalian cells |
AU2003285172A1 (en) | 2002-11-08 | 2004-06-03 | The Johns Hopkins University | Human embryonic stem cell cultures, and compositions and methods for growing same |
US7144999B2 (en) | 2002-11-23 | 2006-12-05 | Isis Pharmaceuticals, Inc. | Modulation of hypoxia-inducible factor 1 alpha expression |
EP1567639A4 (en) | 2002-12-05 | 2005-12-21 | Technion Res & Dev Foundation | CULTURE OF HUMAN PANCREATIC ISLANDS AND USES THEREOF |
JP4613069B2 (ja) | 2002-12-16 | 2011-01-12 | テクニオン リサーチ アンド ディベロップメント ファウンデーション リミテッド | 支持細胞非含有、異種非含有のヒト胚性幹細胞の調製方法およびこれらを使用して調製された幹細胞培養物 |
US20050118148A1 (en) | 2002-12-20 | 2005-06-02 | Roland Stein | Compositions and methods related to mammalian Maf-A |
KR101114808B1 (ko) | 2003-01-29 | 2012-02-15 | 다케다 야쿠힌 고교 가부시키가이샤 | 피복 제제의 제조법 |
RU2359671C2 (ru) | 2003-01-29 | 2009-06-27 | Такеда Фармасьютикал Компани Лимитед | Способ получения препарата с покрытием |
US20070155661A1 (en) | 2003-02-14 | 2007-07-05 | The Board Of Trustees Of The Leland Standord Junior University | Methods and compositions for modulating the development of stem cells |
US20070154981A1 (en) * | 2003-02-14 | 2007-07-05 | The Board Of Trustees Of The Leland Stanford Junior University | Insulin-producing cells derived from stem cells |
CA2520861A1 (en) | 2003-03-27 | 2004-10-14 | Ixion Biotechnology, Inc. | Method for transdifferentiation of non-pancreatic stem cells to the pancreatic pathway |
WO2004090110A2 (en) | 2003-03-31 | 2004-10-21 | Bresagen Inc. | Compositions and methods for the control, differentiation and/or manipulation of pluripotent cells through a gamma-secretase signaling pathway |
US20090203141A1 (en) | 2003-05-15 | 2009-08-13 | Shi-Lung Lin | Generation of tumor-free embryonic stem-like pluripotent cells using inducible recombinant RNA agents |
KR20060021908A (ko) * | 2003-06-23 | 2006-03-08 | 프라운호퍼-게젤샤프트 추르 푀르데룽 데어 안제반텐 포르슝 에 파우 | 췌장 호르몬을 생산하는 세포로 줄기세포를 분화시키는방법 |
EP1641914B1 (en) | 2003-06-27 | 2016-07-20 | DePuy Synthes Products, Inc. | Postpartum cells derived from placental tissue, and methods of making and using the same |
IL161903A0 (en) | 2003-07-17 | 2005-11-20 | Gamida Cell Ltd | Ex vivo progenitor and stem cell expansion for usein the treatment of disease of endodermally- deri ved organs |
ITRM20030395A1 (it) | 2003-08-12 | 2005-02-13 | Istituto Naz Per Le Malattie Infettive Lazz | Terreno di coltura per il mantenimento, la proliferazione e il differenziamento di cellule di mammifero. |
US7569385B2 (en) | 2003-08-14 | 2009-08-04 | The Regents Of The University Of California | Multipotent amniotic fetal stem cells |
US7157275B2 (en) | 2003-08-15 | 2007-01-02 | Becton, Dickinson And Company | Peptides for enhanced cell attachment and growth |
AU2004269395A1 (en) | 2003-08-27 | 2005-03-10 | Stemcells California, Inc. | Enriched pancreatic stem cell and progenitor cell populations, and methods for identifying, isolating and enriching for these populations |
JP2007515433A (ja) | 2003-12-17 | 2007-06-14 | アラーガン インコーポレイテッド | Cyp26aおよびcyp26bの選択的阻害剤を使用するレチノイド反応性障害の処置方法 |
US20060030042A1 (en) | 2003-12-19 | 2006-02-09 | Ali Brivanlou | Maintenance of embryonic stem cells by the GSK-3 inhibitor 6-bromoindirubin-3'-oxime |
US7625753B2 (en) | 2003-12-23 | 2009-12-01 | Cythera, Inc. | Expansion of definitive endoderm cells |
CN112813019A (zh) | 2003-12-23 | 2021-05-18 | 维亚希特公司 | 定形内胚层 |
US7541185B2 (en) | 2003-12-23 | 2009-06-02 | Cythera, Inc. | Methods for identifying factors for differentiating definitive endoderm |
US7704738B2 (en) | 2003-12-23 | 2010-04-27 | Cythera, Inc. | Definitive endoderm |
US20050266554A1 (en) | 2004-04-27 | 2005-12-01 | D Amour Kevin A | PDX1 expressing endoderm |
WO2005065354A2 (en) | 2003-12-31 | 2005-07-21 | The Burnham Institute | Defined media for pluripotent stem cell culture |
TWI334443B (en) | 2003-12-31 | 2010-12-11 | Ind Tech Res Inst | Method of single cell culture of undifferentiated human embryonic stem cells |
US7794704B2 (en) | 2004-01-23 | 2010-09-14 | Advanced Cell Technology, Inc. | Methods for producing enriched populations of human retinal pigment epithelium cells for treatment of retinal degeneration |
WO2005071066A1 (en) | 2004-01-23 | 2005-08-04 | Board Of Regents, The University Of Texas System | Methods and compositions for preparing pancreatic insulin secreting cells |
GB2441530B (en) | 2004-02-12 | 2009-09-23 | Univ Newcastle | Stem Cells |
WO2005080598A1 (ja) | 2004-02-19 | 2005-09-01 | Dainippon Sumitomo Pharma Co., Ltd. | 体細胞核初期化物質のスクリーニング方法 |
AU2005221095A1 (en) | 2004-03-09 | 2005-09-22 | John J. O'neil | Methods for generating insulin-producing cells |
CN1950498A (zh) | 2004-03-10 | 2007-04-18 | 加利福尼亚大学董事会 | 培养胚胎干细胞的组合物和方法 |
KR101178786B1 (ko) | 2004-03-23 | 2012-09-07 | 다이이찌 산쿄 가부시키가이샤 | 다능성 줄기세포의 증식 방법 |
WO2005097980A2 (en) | 2004-03-26 | 2005-10-20 | Geron Corporation | New protocols for making hepatocytes from embryonic stem cells |
WO2005097977A2 (en) | 2004-04-01 | 2005-10-20 | Wisconsin Alumni Research Foundation | Differentiation of stem cells to endoderm and pancreatic lineage |
JP4926946B2 (ja) | 2004-04-27 | 2012-05-09 | ヴィアサイト,インコーポレイテッド | Pdx1発現性内胚葉 |
JP5687816B2 (ja) | 2004-07-09 | 2015-03-25 | ヴィアサイト,インコーポレイテッド | 胚体内胚葉を分化させるための因子を同定する方法 |
JP5102030B2 (ja) | 2004-08-13 | 2012-12-19 | ユニバーシティ・オブ・ジョージア・リサーチ・ファウンデイション・インコーポレイテッド | ヒト胚性幹細胞における自己再生および分化のための組成物および方法 |
US20080268533A1 (en) | 2004-08-25 | 2008-10-30 | University Of Georgia Research Foundation, Inc. | Methods and Compositions Utilizing Myc and Gsk3Beta to Manipulate the Pluripotency of Embryonic Stem Cells |
DE102004043256B4 (de) | 2004-09-07 | 2013-09-19 | Rheinische Friedrich-Wilhelms-Universität Bonn | Skalierbarer Prozess zur Kultivierung undifferenzierter Stammzellen in Suspension |
MX2007002389A (es) | 2004-09-08 | 2009-02-12 | Wisconsin Alumni Res Found | Cultivo de celulas progenitoras embrionarias humanas. |
ES2383813T3 (es) | 2004-09-08 | 2012-06-26 | Wisconsin Alumni Research Foundation | Método de cultivo y cultivo de células madre embrionarias |
AU2006208944A1 (en) | 2005-01-28 | 2006-08-03 | Imperial College Innovations Limited | Methods for embryonic stem cell culture |
AU2006210955A1 (en) | 2005-01-31 | 2006-08-10 | Es Cell International Pte Ltd. | Directed differentiation of embryonic stem cells and uses thereof |
WO2006088867A2 (en) | 2005-02-15 | 2006-08-24 | Medistem Laboratories, Incorporated | Method for expansion of stem cells |
ES2627419T3 (es) | 2005-03-04 | 2017-07-28 | Lifescan, Inc. | Células estromales adultas derivadas del páncreas |
US20060212476A1 (en) | 2005-03-18 | 2006-09-21 | Bogle Phillip L | Method and apparatus for tracking candidate referrers |
GB0505970D0 (en) | 2005-03-23 | 2005-04-27 | Univ Edinburgh | Culture medium containing kinase inhibitor, and uses thereof |
EP1876893B1 (en) | 2005-04-15 | 2012-04-11 | Geron Corporation | Cancer treatment by combined inhibition of proteasome and telomerase activities |
CN100425694C (zh) | 2005-04-15 | 2008-10-15 | 北京大学 | 诱导胚胎干细胞向胰腺细胞分化的方法 |
EP1874367B1 (en) | 2005-04-26 | 2011-07-06 | Arhus Universitet | Biocompatible material for surgical implants and cell guiding tissue culture surfaces |
JP5092124B2 (ja) | 2005-05-24 | 2012-12-05 | 国立大学法人 熊本大学 | Es細胞の分化誘導方法 |
AU2006202209B2 (en) | 2005-05-27 | 2011-04-14 | Lifescan, Inc. | Amniotic fluid derived cells |
MX2007015610A (es) | 2005-06-10 | 2008-02-21 | Irm Llc | Compuestos que mantienen la fluripotencia de las celulas totipotentes embrionarias. |
US20090053181A1 (en) * | 2005-06-13 | 2009-02-26 | Novo Nordisk A/S | Modulation of Cells |
WO2006138433A2 (en) | 2005-06-14 | 2006-12-28 | The Regents Of The University Of California | Induction of cell differentiation by class i bhlh polypeptides |
EP1931764A1 (en) | 2005-06-21 | 2008-06-18 | GE Healthcare Bio-Sciences AB | Method for cell culture |
AU2006262369B2 (en) | 2005-06-22 | 2012-07-05 | Asterias Biotherapeutics, Inc. | Suspension culture of human embryonic stem cells |
NZ564179A (en) | 2005-06-30 | 2010-09-30 | Janssen Pharmaceutica Nv | Cyclic anilino - pyridinotriazines as GSK-3 inhibitors |
US20080194021A1 (en) | 2005-07-29 | 2008-08-14 | Mays Robert W | Use of a Gsk-3 Inhibitor to Maintain Potency of Culture Cells |
CA2616863A1 (en) | 2005-07-29 | 2007-02-01 | Australian Stem Cell Centre Limited | Compositions and methods for growth of pluripotent cells |
WO2007025234A2 (en) | 2005-08-26 | 2007-03-01 | The Trustees Of Columbia University In The City Of New York | Generation of pancreatic endocrine cells from primary duct cell cultures and methods of use for treatment of diabetes |
US8476070B2 (en) | 2005-08-29 | 2013-07-02 | Technion Research & Development Foundation Limited | Media for culturing stem cells |
KR20080056181A (ko) | 2005-09-02 | 2008-06-20 | 에이전시 포 사이언스, 테크놀로지 앤드 리서치 | 전구세포주의 유도 방법 |
GB2444686B (en) | 2005-09-12 | 2010-08-25 | Es Cell Int Pte Ltd | Differentiation of pluripotent stem cells using p38 MAPK inhibitors or prostaglandins |
KR20130066707A (ko) * | 2005-09-21 | 2013-06-20 | 다스크 테크날러지, 엘엘씨 | 장기 및 조직 기능성을 위한 방법 및 조성물 |
CN101310012B (zh) | 2005-10-14 | 2012-05-09 | 明尼苏达大学董事会 | 非胚胎干细胞分化成具有胰腺表型的细胞 |
US7732202B2 (en) | 2005-10-21 | 2010-06-08 | International Stem Cell Corporation | Oxygen tension for the parthenogenic activation of human oocytes for the production of human embryonic stem cells |
US20070122905A1 (en) | 2005-10-27 | 2007-05-31 | D Amour Kevin A | PDX1-expressing dorsal and ventral foregut endoderm |
UA96139C2 (uk) * | 2005-11-08 | 2011-10-10 | Дженентек, Інк. | Антитіло до нейропіліну-1 (nrp1) |
EP2206724A1 (en) | 2005-12-13 | 2010-07-14 | Kyoto University | Nuclear reprogramming factor |
WO2007082963A1 (es) | 2006-01-18 | 2007-07-26 | Fundación Instituto Valenciano De Infertilidad | Líneas de células madre embrionarias humanas y métodos para usar las mismas |
EP1994141B1 (en) | 2006-02-23 | 2017-11-15 | ViaCyte, Inc. | Compositions and methods useful for culturing differentiable cells |
US7695965B2 (en) | 2006-03-02 | 2010-04-13 | Cythera, Inc. | Methods of producing pancreatic hormones |
WO2007103282A2 (en) * | 2006-03-02 | 2007-09-13 | Cythera, Inc. | Endocrine precursor cells, pancreatic hormone-expressing cells and methods of production |
CA2650812C (en) | 2006-04-28 | 2017-12-12 | Lifescan, Inc. | Differentiation of human embryonic stem cells |
US8741643B2 (en) | 2006-04-28 | 2014-06-03 | Lifescan, Inc. | Differentiation of pluripotent stem cells to definitive endoderm lineage |
US20070259423A1 (en) | 2006-05-02 | 2007-11-08 | Jon Odorico | Method of differentiating stem cells into cells of the endoderm and pancreatic lineage |
US8685730B2 (en) | 2006-05-02 | 2014-04-01 | Wisconsin Alumni Research Foundation | Methods and devices for differentiating pluripotent stem cells into cells of the pancreatic lineage |
WO2007136673A2 (en) | 2006-05-19 | 2007-11-29 | Medistem Laboratories, Inc. | Treatment of disc degenerative disease and compositions for same |
WO2007139929A2 (en) | 2006-05-25 | 2007-12-06 | The Burnham Institute For Medical Research | Methods for culture and production of single cell populations of human embryonic stem cells |
CN101541953A (zh) | 2006-06-02 | 2009-09-23 | 佐治亚大学研究基金会 | 通过从人胚胎干细胞获得的定形内胚层细胞的分化得到胰和肝内胚层细胞及组织 |
AU2007254766A1 (en) | 2006-06-02 | 2007-12-13 | University Of Georgia Research Foundation, Inc. | Pancreatic and liver endoderm cells and tissue by differentiation of definitive endoderm cells obtained from human embryonic stems |
US8415153B2 (en) * | 2006-06-19 | 2013-04-09 | Geron Corporation | Differentiation and enrichment of islet-like cells from human pluripotent stem cells |
CN100494359C (zh) | 2006-06-23 | 2009-06-03 | 中日友好医院 | 神经干细胞三维立体培养体外扩增的方法 |
EP2046946B8 (en) | 2006-06-26 | 2017-01-25 | Lifescan, Inc. | Pluripotent stem cell culture |
US20080003676A1 (en) | 2006-06-26 | 2008-01-03 | Millipore Corporation | Growth of embryonic stem cells |
US8968994B2 (en) | 2006-07-06 | 2015-03-03 | Jeremy Micah Crook | Method for stem cell culture and cells derived therefrom |
AU2007277364B2 (en) | 2006-07-26 | 2010-08-12 | Viacyte, Inc. | Methods of producing pancreatic hormones |
ES2704401T3 (es) | 2006-08-02 | 2019-03-18 | Technion Res & Dev Foundation | Métodos de expansión de células madre embrionarias en un cultivo en suspensión |
KR101331510B1 (ko) | 2006-08-30 | 2013-11-20 | 재단법인서울대학교산학협력재단 | 저농도의 포도당을 함유하는 인간 배아줄기세포용 배지조성물 및 이를 이용한 인간 배아 줄기세포로부터 인슐린생산 세포 또는 세포괴로 분화시키는 방법, 그리고그로부터 유도된 인슐린 생산 세포 또는 세포괴 |
JP2008099662A (ja) | 2006-09-22 | 2008-05-01 | Institute Of Physical & Chemical Research | 幹細胞の培養方法 |
US20080091234A1 (en) | 2006-09-26 | 2008-04-17 | Kladakis Stephanie M | Method for modifying a medical implant surface for promoting tissue growth |
MX2009004096A (es) | 2006-10-17 | 2009-06-16 | Stiefel Laboratories | Metabolitos de talarozol. |
US20100323442A1 (en) | 2006-10-17 | 2010-12-23 | Emmanuel Edward Baetge | Modulation of the phosphatidylinositol-3-kinase pathway in the differentiation of human embryonic stem cells |
CA2666789C (en) | 2006-10-18 | 2016-11-22 | Yong Zhao | Embryonic-like stem cells derived from adult human peripheral blood and methods of use |
US20110151554A1 (en) | 2006-11-09 | 2011-06-23 | Akira Yuo | Method for culturing and subculturing primate embryonic stem cell, as well as method for inducing differentiation thereof |
TW200836749A (en) | 2007-01-09 | 2008-09-16 | Vioquest Pharmaceuticals Inc | Compositions including triciribine and bortezomib and derivatives thereof and methods of use thereof |
EP1947193A1 (en) * | 2007-01-17 | 2008-07-23 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Screening method for anti-diabetic compounds |
CN103627671A (zh) | 2007-01-30 | 2014-03-12 | 佐治亚大学研究基金会 | 产生中内胚层细胞及多能游走细胞的方法与细胞群及用途 |
GB0703188D0 (en) | 2007-02-19 | 2007-03-28 | Roger Land Building | Large scale production of stem cells |
US20090053182A1 (en) | 2007-05-25 | 2009-02-26 | Medistem Laboratories, Inc. | Endometrial stem cells and methods of making and using same |
CA2691793A1 (en) | 2007-06-29 | 2009-01-08 | Cellular Dynamics International, Inc. | Automated method and apparatus for embryonic stem cell culture |
EP3957716A1 (en) | 2007-07-18 | 2022-02-23 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
EP2185691B1 (en) | 2007-07-31 | 2018-03-14 | Lifescan, Inc. | Pluripotent stem cell differentiation by using human feeder cells |
EP2185693B1 (en) | 2007-07-31 | 2019-07-03 | Lifescan, Inc. | Differentiation of human embryonic stem cells |
KR101544498B1 (ko) | 2007-08-24 | 2015-08-17 | 스티칭 허트 네덜란드 칸커 인스티튜트 | 종양성 질환의 치료를 위한 조성물 |
US20110151447A1 (en) | 2007-11-06 | 2011-06-23 | Children's Medical Center Corporation | Method to produce induced pluripotent stem (ips) cells from non-embryonic human cells |
US9062290B2 (en) | 2007-11-27 | 2015-06-23 | Lifescan, Inc. | Differentiation of human embryonic stem cells |
SG154367A1 (en) | 2008-01-31 | 2009-08-28 | Es Cell Int Pte Ltd | Method of differentiating stem cells |
WO2009096049A1 (ja) | 2008-02-01 | 2009-08-06 | Kyoto University | 人工多能性幹細胞由来分化細胞 |
EP2250252A2 (en) | 2008-02-11 | 2010-11-17 | Cambridge Enterprise Limited | Improved reprogramming of mammalian cells, and the cells obtained |
MX2010009251A (es) | 2008-02-21 | 2010-11-25 | Centocor Ortho Biotech Inc | Metodos, placas de superficie modificada y composiciones para la fijacion, el cultivo y el desprendimiento celular. |
JPWO2009110215A1 (ja) | 2008-03-03 | 2011-07-14 | 独立行政法人科学技術振興機構 | 繊毛細胞の分化誘導方法 |
EP2479260B1 (en) | 2008-03-17 | 2016-01-06 | Agency For Science, Technology And Research | Microcarriers for stem cell culture |
RU2359030C1 (ru) | 2008-03-19 | 2009-06-20 | Общество С Ограниченной Ответственностью "Лаборатория Клеточных Технологий" | Способ получения эндотелиальных клеток из эмбриональных стволовых клеток человека (варианты) |
US8338170B2 (en) | 2008-04-21 | 2012-12-25 | Viacyte, Inc. | Methods for purifying endoderm and pancreatic endoderm cells derived from human embryonic stem cells |
DK2283117T3 (da) | 2008-04-21 | 2014-01-20 | Viacyte Inc | Fremgangsmåde til oprensning af pancreatiske endodermceller afledt fra humane embryoniske stamceller |
WO2009132083A2 (en) | 2008-04-22 | 2009-10-29 | President And Fellows Of Harvard College | Compositions and methods for promoting the generation of pdx1+ pancreatic cells |
US8623648B2 (en) | 2008-04-24 | 2014-01-07 | Janssen Biotech, Inc. | Treatment of pluripotent cells |
US7939322B2 (en) | 2008-04-24 | 2011-05-10 | Centocor Ortho Biotech Inc. | Cells expressing pluripotency markers and expressing markers characteristic of the definitive endoderm |
US20090298178A1 (en) | 2008-06-03 | 2009-12-03 | D Amour Kevin Allen | Growth factors for production of definitive endoderm |
WO2009154606A1 (en) | 2008-06-03 | 2009-12-23 | Cythera, Inc. | Growth factors for production of definitive endoderm |
CA2729734A1 (en) * | 2008-06-30 | 2010-01-07 | Centocor Ortho Biotech Inc. | Differentiation of pluripotent stem cells |
ES2697798T3 (es) | 2008-06-30 | 2019-01-28 | Janssen Biotech Inc | Diferenciación de células madre pluripotentes |
DE102008032236A1 (de) | 2008-06-30 | 2010-04-01 | Eberhard-Karls-Universität Tübingen | Isolierung und/oder Identifizierung von Stammzellen mit adipozytärem, chondrozytärem und pankreatischem Differenzierungspotential |
US20100028307A1 (en) | 2008-07-31 | 2010-02-04 | O'neil John J | Pluripotent stem cell differentiation |
WO2010022395A2 (en) | 2008-08-22 | 2010-02-25 | President And Fellows Of Harvard College | Methods of reprogramming cells |
CA2742268C (en) | 2008-10-31 | 2020-02-18 | Centocor Ortho Biotech Inc. | Differentiation of human embryonic stem cells to the pancreatic endocrine lineage |
CN102333862B (zh) * | 2008-10-31 | 2018-04-27 | 詹森生物科技公司 | 人胚胎干细胞向胰腺内分泌谱系的分化 |
CA2742583C (en) | 2008-11-04 | 2022-09-27 | Viacyte, Inc. | Stem cell aggregate suspension compositions and methods for differentiation thereof |
US8008075B2 (en) | 2008-11-04 | 2011-08-30 | Viacyte, Inc. | Stem cell aggregate suspension compositions and methods of differentiation thereof |
JP2012508584A (ja) | 2008-11-14 | 2012-04-12 | ヴィアサイト,インコーポレイテッド | ヒト多能性幹細胞由来膵臓細胞のカプセル化 |
AU2009316580B2 (en) | 2008-11-20 | 2016-04-14 | Janssen Biotech, Inc. | Pluripotent stem cell culture on micro-carriers |
WO2010063848A1 (en) | 2008-12-05 | 2010-06-10 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method and medium for neural differentiation of pluripotent cells |
US9109245B2 (en) * | 2009-04-22 | 2015-08-18 | Viacyte, Inc. | Cell compositions derived from dedifferentiated reprogrammed cells |
EP2456858B1 (en) * | 2009-07-20 | 2018-08-29 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
GB2485113B (en) | 2009-07-20 | 2016-12-28 | Janssen Biotech Inc | Differentiation of human embryonic stem cells into cells of the pancreatic endoderm lineage |
KR20170118969A (ko) | 2009-07-20 | 2017-10-25 | 얀센 바이오테크 인코포레이티드 | 인간 배아 줄기 세포의 분화 |
KR101861584B1 (ko) | 2009-10-29 | 2018-05-28 | 얀센 바이오테크 인코포레이티드 | 만능 줄기 세포 |
FI20096288A0 (fi) | 2009-12-04 | 2009-12-04 | Kristiina Rajala | Formulations and methods for culturing stem cells |
PL2516626T3 (pl) | 2009-12-23 | 2017-10-31 | Janssen Biotech Inc | Różnicowanie ludzkich zarodkowych komórek macierzystych |
WO2011079017A2 (en) | 2009-12-23 | 2011-06-30 | Centocor Ortho Biotech Inc. | Differentiation of human embryonic stem cells |
US8932853B2 (en) * | 2009-12-29 | 2015-01-13 | Takeda Pharmaceutical Company Limited | Method for manufacturing pancreatic-hormone-producing cells |
JP5812492B2 (ja) | 2010-02-03 | 2015-11-11 | 国立研究開発法人国立がん研究センター | 誘導肝幹細胞及びその製造方法、並びに、該細胞の応用 |
SG10201501513TA (en) | 2010-03-02 | 2015-04-29 | Univ Singapore | Culture additives to boost stem cell proliferation and differentiation response |
JP5909482B2 (ja) | 2010-03-31 | 2016-04-26 | ザ スクリプス リサーチ インスティテュート | 細胞の再プログラム |
JP2013524836A (ja) | 2010-04-25 | 2013-06-20 | マウント・シナイ・スクール・オブ・メディスン | 多能性細胞からの前部前腸内胚葉の生成 |
RU2663339C1 (ru) | 2010-05-12 | 2018-08-03 | Янссен Байотек, Инк. | Дифференцирование эмбриональных стволовых клеток человека |
US9085757B2 (en) * | 2010-06-17 | 2015-07-21 | Regents Of The University Of Minnesota | Production of insulin producing cells |
KR101829488B1 (ko) | 2010-08-05 | 2018-02-14 | 위스콘신 얼럼나이 리서어치 화운데이션 | 인간 다분화능 세포 배양을 위한 단순화된 기본 배지 |
JP5881606B2 (ja) * | 2010-08-06 | 2016-03-09 | 大日本住友製薬株式会社 | 脊髄損傷治療用製剤 |
EP2611910B1 (en) | 2010-08-31 | 2018-01-17 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells |
BR112013004614A2 (pt) | 2010-08-31 | 2024-01-16 | Janssen Biotech Inc | Diferenciação de células-tronco pluripotentes |
MY177150A (en) | 2011-02-28 | 2020-09-08 | Stempeutics Res Malaysia Sdn Bhd | Isolation and expansion of adult stem cells, their therapeutic composition and uses thereof |
US20130274184A1 (en) | 2011-10-11 | 2013-10-17 | The Trustees Of Columbia University In The City Of New York | Er stress relievers in beta cell protection |
US9670463B2 (en) | 2011-10-14 | 2017-06-06 | Children's Medical Center Corporation | Inhibition and enhancement of reprogramming by chromatin modifying enzymes |
JP6441080B2 (ja) | 2011-12-22 | 2018-12-19 | ヤンセン バイオテツク,インコーポレーテツド | 単一ホルモンのインスリン陽性細胞へのヒト胚性幹細胞の分化 |
US10519422B2 (en) | 2012-02-29 | 2019-12-31 | Riken | Method of producing human retinal pigment epithelial cells |
EP2859091B1 (en) * | 2012-06-08 | 2018-08-29 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells into pancreatic endocrine cells |
JP6470687B2 (ja) | 2012-09-03 | 2019-02-13 | ノヴォ ノルディスク アー/エス | 小分子を用いた多能性幹細胞からの膵臓内胚葉の作製 |
RU2684215C2 (ru) | 2012-12-31 | 2019-04-04 | Янссен Байотек, Инк. | Способ получения панкреатических эндокринных клеток (варианты) и способ увеличения выхода бета-клеток |
US8859286B2 (en) | 2013-03-14 | 2014-10-14 | Viacyte, Inc. | In vitro differentiation of pluripotent stem cells to pancreatic endoderm cells (PEC) and endocrine cells |
AU2014239954B2 (en) | 2013-03-15 | 2020-07-16 | The Jackson Laboratory | Isolation of non-embryonic stem cells and uses thereof |
CN105233291A (zh) * | 2014-07-09 | 2016-01-13 | 博笛生物科技有限公司 | 用于治疗癌症的联合治疗组合物和联合治疗方法 |
CN110582564A (zh) * | 2015-09-15 | 2019-12-17 | 新加坡科技研究局 | 从人类多能干细胞衍生肝类器官 |
JP7389980B2 (ja) * | 2018-12-06 | 2023-12-01 | 国立大学法人 琉球大学 | ヒト膵臓組織特異的幹/前駆細胞の人工作製方法 |
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