MilliporeSigma
  • Home
  • Search Results
  • Large-scale Generation of Functional and Transplantable Hepatocytes and Cholangiocytes from Human Endoderm Stem Cells.

Large-scale Generation of Functional and Transplantable Hepatocytes and Cholangiocytes from Human Endoderm Stem Cells.

Cell reports (2020-12-10)
Sisi Feng, Jiaying Wu, Wei-Lin Qiu, Li Yang, Xiaogang Deng, Ying Zhou, Yabin Chen, Xiao Li, Lei Yu, Hongsheng Li, Zi-Ran Xu, Yini Xiao, Xiongzhao Ren, Ludi Zhang, Chenhua Wang, Zhen Sun, Jinglin Wang, Xiaoyan Ding, Yuelei Chen, Paul Gadue, Guoyu Pan, Mina Ogawa, Shinichiro Ogawa, Jie Na, Peilin Zhang, Lijian Hui, Hao Yin, Luonan Chen, Cheng-Ran Xu, Xin Cheng
ABSTRACT

The ever-increasing therapeutic and pharmaceutical demand for liver cells calls for systems that enable mass production of hepatic cells. Here we describe a large-scale suspension system that uses human endoderm stem cells (hEnSCs) as precursors to generate functional and transplantable hepatocytes (E-heps) or cholangiocytes (E-chos). hEnSC-derived hepatic populations are characterized by single-cell transcriptomic analyses and compared with hESC-derived counterparts, in-vitro-maintained or -expanded primary hepatocytes and adult cells, which reveals that hepatic differentiation of hEnSCs recapitulates in vivo development and that the heterogeneities of the resultant populations can be manipulated by regulating the EGF and MAPK signaling pathways. Functional assessments demonstrate that E-heps and E-chos possess properties comparable with adult counterparts and that, when transplanted intraperitoneally, encapsulated E-heps were able to rescue rats with acute liver failure. Our study lays the foundation for cell-based therapeutic agents and in vitro applications for liver diseases.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Magnesium chloride solution, BioUltra, for molecular biology, 2 M in H2O
Sigma-Aldrich
Secretin human, ≥97% (HPLC), powder
Sigma-Aldrich
1,2-Dilinoleoyl-3-palmitoyl-rac-glycerol, ≥95% (TLC), liquid
Sigma-Aldrich
Collagenase from Clostridium histolyticum, suitable for release of physiologically active rat hepatocytes, Type IV, 0.5-5.0 FALGPA units/mg solid, ≥125 CDU/mg solid
Sigma-Aldrich
Collagenase from Clostridium histolyticum, for general use, Type I, 0.25-1.0 FALGPA units/mg solid, ≥125 CDU/mg solid
Sigma-Aldrich
Amiodarone hydrochloride, ≥98%
Sigma-Aldrich
[Leu15]-Gastrin I human, ≥95% (HPLC)
Sigma-Aldrich
Diclofenac sodium salt
Sigma-Aldrich
Retinoic acid, ≥98% (HPLC), powder
Sigma-Aldrich
(±)-Verapamil hydrochloride, ≥99% (titration), powder
Sigma-Aldrich
DAPT, ≥98% (HPLC), solid
Sigma-Aldrich
Nicotinamide, BioReagent, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
Poly-L-lysine hydrochloride, mol wt 15,000-30,000
Sigma-Aldrich
Dexamethasone, ≥98% (HPLC), powder
Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
Triton X-100, BioXtra
Sigma-Aldrich
L-(−)-Glucose, ≥99%
Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Sigma-Aldrich
Adenosine 3′,5′-cyclic monophosphate tris salt, ≥97% (HPLC), powder
Sigma-Aldrich
N-Acetyl-L-cysteine, Sigma Grade, ≥99% (TLC), powder
Supelco
Acetaminophen, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Chlorpromazine hydrochloride, meets USP testing specifications
Sigma-Aldrich
γ-Secretase Inhibitor XXI, Compound E - CAS 209986-17-4 - Calbiochem, This g-secretase inhibitor, CAS 209986-17-4, is a cell-permeable, potent, selective, non-transition-state analog inhibitor of γ-secretase and Notch processing. Lowers Aβ levels in APP transgenic mice
Sigma-Aldrich
α-Amyloid Precursor Protein Modulator - CAS 497259-23-1 - Calbiochem, A cell-permeable benzolactam derived PKC activator (Ki = 11.9 nM for PKCα) that efficiently enhances non-amyloidogenic α-processing of amyloid precursor protein (APP) even at 100 nM in human fibroblast AG06848.
Sigma-Aldrich
Sodium alginate