Dataset Information

Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy.

ABSTRACT:

Background

Various methods have been developed to generate hepatic cells from human pluripotent stem cells (hPSCs) that rely on the combined use of multiple expensive growth factors, limiting industrial-scale production and widespread applications. Small molecules offer an attractive alternative to growth factors for producing hepatic cells since they are more economical and relatively stable.

Methods

We dissect small-molecule combinations and identify the ideal cocktails to achieve an optimally efficient and cost-effective strategy for hepatic cells differentiation, expansion, and maturation.

Results

We demonstrated that small-molecule cocktail CIP (including CHIR99021, IDE1, and PD0332991) efficiently induced definitive endoderm (DE) formation via increased endogenous TGF-β/Nodal signaling. Furthermore, we identified that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute growth factors to induce hepatic specification. The obtained hepatoblasts (HBs) could subsequently expand and mature into functional hepatocyte-like cells (HLCs) by the established chemical formulas. Thus, we established a stepwise strategy with complete small molecules for efficiently producing scalable HBs and functionally matured HLCs. The small-molecule-derived HLCs displayed typical functional characteristics as mature hepatocytes in vitro and repopulating injured liver in vivo.

Conclusion

Our current small-molecule-based hepatic generation protocol presents an efficient and cost-effective platform for the large-scale production of functional human hepatic cells for cell-based therapy and drug discovery using.

SUBMITTER: Pan T

PROVIDER: S-EPMC8996222 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy.

Pan Tingcai T Wang Ning N Zhang Jiaye J Yang Fan F Chen Yan Y Zhuang Yuanqi Y Xu Yingying Y Fang Ji J You Kai K Lin Xianhua X Li Yang Y Li Shao S Liang Kangyan K Li Yin-Xiong YX Gao Yi Y

Stem cell research & therapy 20220411 1

<h4>Background</h4>Various methods have been developed to generate hepatic cells from human pluripotent stem cells (hPSCs) that rely on the combined use of multiple expensive growth factors, limiting industrial-scale production and widespread applications. Small molecules offer an attractive alternative to growth factors for producing hepatic cells since they are more economical and relatively stable.<h4>Methods</h4>We dissect small-molecule combinations and identify the ideal cocktails to achie ...[more]

PMID: 35410439

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Project description:UnlabelledThe recapitulation of human neural development in a controlled, defined manner from pluripotent stem cells (PSCs) has considerable potential for studies of human neural development, circuit formation and function, and the construction of in vitro models of neurological diseases. The inhibition of Wnt signaling, often by the recombinant protein DKK1, is important for the induction of cortical neurons. Here, we report a novel differentiation method using a small-molecule WNT inhibitor, WNT-C59 (C59), to efficiently induce human anterior cortex. We compared two types of small molecules, C59 and XAV939 (XAV), as substitutes for DKK1 to induce cortical neurons from PSCs in serum-free embryoid body-like aggregate culture. DKK1 and XAV inhibited only the canonical pathway of Wnt signaling, whereas C59 inhibited both the canonical and noncanonical pathways. C59 efficiently induced CTIP2+/COUP-TF1- cells, which are characteristic of the cells found in the anterior cortex. In addition, when grafted into the cortex of adult mice, the C59-induced cells showed abundant axonal fiber extension toward the spinal cord. These results raise the possibility of C59 contributing to cell replacement therapy for motor neuron diseases or insults.SignificanceFor a cell therapy against damaged corticospinal tract caused by neurodegenerative diseases or insults, cortical motor neurons are needed. Currently, their induction from pluripotent stem cells is considered very promising; however, an efficient protocol to induce motor neurons is not available. For efficient induction of anterior cortex, where motor neurons are located, various WNT inhibitors were investigated. It was found that one of them could induce anterior cortical cells efficiently. In addition, when grafted into the cortex of adult mice, the induced cells showed more abundant axonal fiber extension toward spinal cord. These results raise the possibility that this inhibitor contributes to a cell-replacement therapy for motor neuron diseases or insults.

Dataset Information

Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy.

Background

Methods

Results

Conclusion

Publications

Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy.

Similar Datasets

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