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

The study suggests that small molecules, including Dihexa, can be used to generate functional hepatic cells from human pluripotent stem cells, but specific efficacy metrics are not provided.

Summary and findings

This study investigated the generation of hepatic cells from human pluripotent stem cells (hPSCs) using small-molecule strategies. The authors reported that a combination of small molecules, including Dihexa, could effectively induce hepatic specification. The findings suggest a potential method for scalable production of functional hepatic cells.

Abstract

<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 achieve an optimally efficient and cost-effective strategy for hepatic cells differentiation, expansion, and maturation.<h4>Results</h4>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.<h4>Conclusion</h4>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.

Key findings

• Not reported in abstract.

Limitations

• Not reported in abstract.

Elsewhere in the Dihexa corpus