CN115386535A - 多谱系肝类器官模型及基于该模型的药物肝毒评价方法 - Google Patents
多谱系肝类器官模型及基于该模型的药物肝毒评价方法 Download PDFInfo
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Abstract
Description
试剂耗材名称 | 公司(货号) |
mTeSR1 | STEMCELL (85850) |
Y-27632 | TOCRIS (1254/1) |
RPMI 1640 | Gibco (31870082) |
F12 | Gibco (11765062) |
William’s E | Gibco (22551022) |
EGM-2 | Lonza (CC-3162) |
Accutase-EDTA | Innovative Cell Technologies (12605010) |
HepatoZYME | Gibco (17705021) |
KSR | Gibco (10828010) |
ITS | Gibco (41400045) |
rhGDF8 | R&D (788-G8) |
rhBMP4 | R&D (314-BPE) |
rhFGF2 | R&D (233-FB) |
rhFGF4 | R&D (235-F4) |
rhNOG | R&D (6057-NG) |
rhEGF | R&D (236-EG) |
rhVEGF | R&D (DVE00) |
rhOSM | R&D (295-OM) |
CC | TOCRIS (3093/10) |
CHIR99021 | TOCRIS (4423/10) |
NIC | TOCRIS (4106/50) |
ATRA | TOCRIS (0695/50) |
LCA | Sigma (L6250) |
RepSox | TOCRIS (3742/10) |
8-Br-cAMP | TOCRIS (1140/10) |
Dihexa | InvivoChem (V15953) |
SB431542 | TOCRIS (1614) |
MK4 | Sigma (V9378) |
MK125 | TOCRIS (0884/5) |
Cultrex Reduced Growth Factor Basement Membrane Extract, Type 2, Pathclear | R&D (3533-010-02) |
Human liver RNA | Clontech (636531) |
Trizol Solution | Invitrogen (15596018) |
Evo M-MLV RT Kit with gDNA Clean for qPCR | AG (AG11705) |
SYBR Green Premix Pro Taq HS qPCR Kit | AG (AG11718) |
Normal Donkey Serum | Jacksonlab (017-000-121) |
DAPI | Sigma (D9542) |
Rifampicin | TOCRIS (4121/50) |
Acetaminophen | TOCRIS (1706/100) |
Cyclosporin A | TOCRIS (1101/100) |
Troglitazone | TOCRIS (3114/10) |
Rosiglitazone | TOCRIS (5325/10) |
Trovafloxacin | TOCRIS (3863/10) |
Levofloxacin | Sigma (1362103) |
Dispase II | Gibco (17105041) |
CellTiter-Glo® 3D Cell Viability Assay | Promega (G9682) |
P450-Glo™ CYP3A4 Assay and Screening System kit | Promega (V9002) |
AST Activity Assay Kit | Sigma (MAK055) |
ALT Activity Assay Kit | Sigma (MAK052) |
Cultrex Reduced Growth Factor Basement Membrane Extract, Type 2, Pathclear | R&D (3533-010-02) |
Total bile acids(TBA) Assay kit (Colorimetric) | Biovision(ab239702) |
Oxygen Consumption Rate Assay Kit | Cayman(600800) |
CDFDA | Sigma (21884-100MG) |
CLF(Cholyl-lys-Fluluorescein) | AAT Bioquest (36701) |
Image-iT™ TMRM 试剂 | Invitrogen (I34361) |
rhNOG | 重组人头蛋白;BMP抑制剂 |
rhGDF8 | 肌肉抑制素8 |
rhBMP4 | 重组人骨形成蛋白4 |
rhFGF2 | 重组人成纤维细胞生长因子2 |
rhFGF4 | 重组人成纤维细胞生长因子4 |
rhEGF | 重组人上皮生长因子 |
rhVEGF | 重组人血管内皮细胞生长因子 |
KSR (KnockOut Serum Replacement) | Knockout血清替代物 |
CHIR99021 | GSK-3抑制剂 |
NIC (Nicotinamide) | 烟酰胺,SIRT1抑制剂 |
ATRA (All-trans-Retinoic acid) | 全反式维甲酸,RAR核受体的天然激动剂 |
LCA (Lithocholic acid) | 石胆酸 |
RepSox | TGFβR-1/ALK5抑制剂 |
William’s E | 一种使用于上皮细胞/上皮干细胞的基础培养基 |
F12 | Ham营养混合物 |
HepatoZYME | 一种适用于维持肝系基因型维持的无血清培养基 |
ITS (Insulin-Transferrin-Selenium) | 胰岛素-转铁蛋白-硒混合液 |
cAMP | PKA激活剂 |
MK4 (Menaquinone-4) | 甲萘醌 4 |
MX (Methoxamine) | 甲氧胺,α1-肾上腺素能受体激动剂 |
MK125 (Dexamethasone) | 地塞米松 |
PH (Primary hepatocyte) | 人原代肝细胞 |
SB-431542 | 选择性的ALK5/TGF-β type I Receptor抑制剂 |
Dihexa | 可渗透血脑屏障的,血管紧张素IV类似物,对肝细胞生长因子(HGF)具有高亲和力 |
TC50 | 50%毒性浓度 |
ALT | 谷丙转氨酶 |
AST | 天冬氨酸转氨酶 |
Rifampicin | 利福平 |
Acetaminophen | 对乙酰氨基酚 |
Cyclosporin A | 环孢菌素A |
Troglitazone | 曲格列酮 |
Rosiglitazone | 罗格列酮 |
Trovafloxacin | 曲伐沙星 |
Levofloxacin | 左氧氟沙星 |
Dispase II | 分散酶II |
DMSO | 二甲基亚砜 |
Cmax | 药物最大血浆浓度 |
EGM-2 | 内皮细胞培养基 |
CDFDA | 5[6]-羧基-2',7'-二氯荧光素二乙酸酯 |
OCR | 耗氧率 |
TBA | 总胆汁酸 |
BSEP | 胆汁酸转运泵 |
Claims (13)
Priority Applications (1)
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115786245A (zh) * | 2023-02-13 | 2023-03-14 | 淇嘉科技(天津)有限公司 | 人仿生肺脏类器官构建方法 |
CN115786244A (zh) * | 2023-02-13 | 2023-03-14 | 淇嘉科技(天津)有限公司 | 抗肺纤维化药效筛选流程 |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102858985A (zh) * | 2009-07-24 | 2013-01-02 | 西格马-奥尔德里奇有限责任公司 | 基因组编辑方法 |
CN105793414A (zh) * | 2013-10-09 | 2016-07-20 | 剑桥企业有限公司 | 前肠干细胞的活体外生产 |
US20180258400A1 (en) * | 2015-09-15 | 2018-09-13 | Agency For Science, Technology And Research (A*Star) | Derivation of liver organoids from human pluripotent stem cells |
CN110381967A (zh) * | 2016-11-04 | 2019-10-25 | 儿童医院医学中心 | 肝类器官组合物以及其制备和使用方法 |
US20200199537A1 (en) * | 2017-06-09 | 2020-06-25 | Children's Hospital Medical Center | Liver organoid compositions and methods of making and using same |
CN111979183A (zh) * | 2020-08-10 | 2020-11-24 | 创芯国际生物科技(广州)有限公司 | 一种基于肝脏类器官模型的药物肝毒性评价方法 |
US20210147831A1 (en) * | 2018-04-27 | 2021-05-20 | The Broad Institute, Inc. | Sequencing-based proteomics |
CN114149961A (zh) * | 2022-02-09 | 2022-03-08 | 天九再生医学(天津)科技有限公司 | 一种多谱系肝脏类器官及其构建方法和应用 |
WO2022075943A1 (en) * | 2020-10-08 | 2022-04-14 | Dokuz Eylül Üni̇versi̇tesi̇ Rektörlüğü | Long-term and functional culture of hepatic organoids (ehepo) derived from epcam+ endodermal progenitor cells differentiated from induced pluripotent stem cells |
WO2022181880A1 (ko) * | 2021-02-24 | 2022-09-01 | 한국화학연구원 | 인간 전분화능 줄기세포 유래 약물 대사능이 증진된 간 오가노이드의 제조 방법 및 상기 방법으로 제조된 간 오가노이드 |
-
2022
- 2022-10-26 CN CN202211314796.9A patent/CN115386535B/zh active Active
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102858985A (zh) * | 2009-07-24 | 2013-01-02 | 西格马-奥尔德里奇有限责任公司 | 基因组编辑方法 |
CN105793414A (zh) * | 2013-10-09 | 2016-07-20 | 剑桥企业有限公司 | 前肠干细胞的活体外生产 |
US20180258400A1 (en) * | 2015-09-15 | 2018-09-13 | Agency For Science, Technology And Research (A*Star) | Derivation of liver organoids from human pluripotent stem cells |
CN110381967A (zh) * | 2016-11-04 | 2019-10-25 | 儿童医院医学中心 | 肝类器官组合物以及其制备和使用方法 |
US20200199537A1 (en) * | 2017-06-09 | 2020-06-25 | Children's Hospital Medical Center | Liver organoid compositions and methods of making and using same |
US20210147831A1 (en) * | 2018-04-27 | 2021-05-20 | The Broad Institute, Inc. | Sequencing-based proteomics |
CN111979183A (zh) * | 2020-08-10 | 2020-11-24 | 创芯国际生物科技(广州)有限公司 | 一种基于肝脏类器官模型的药物肝毒性评价方法 |
WO2022075943A1 (en) * | 2020-10-08 | 2022-04-14 | Dokuz Eylül Üni̇versi̇tesi̇ Rektörlüğü | Long-term and functional culture of hepatic organoids (ehepo) derived from epcam+ endodermal progenitor cells differentiated from induced pluripotent stem cells |
WO2022181880A1 (ko) * | 2021-02-24 | 2022-09-01 | 한국화학연구원 | 인간 전분화능 줄기세포 유래 약물 대사능이 증진된 간 오가노이드의 제조 방법 및 상기 방법으로 제조된 간 오가노이드 |
CN114149961A (zh) * | 2022-02-09 | 2022-03-08 | 天九再生医学(天津)科技有限公司 | 一种多谱系肝脏类器官及其构建方法和应用 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115786245A (zh) * | 2023-02-13 | 2023-03-14 | 淇嘉科技(天津)有限公司 | 人仿生肺脏类器官构建方法 |
CN115786244A (zh) * | 2023-02-13 | 2023-03-14 | 淇嘉科技(天津)有限公司 | 抗肺纤维化药效筛选流程 |
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