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

Pan T, Wang N, Zhang J, Yang F, Chen Y, Zhuang Y, Xu Y, Fang J, You K, Lin X, Li Y, Li S, Liang K, Li YX, Gao Y

Stem cell research & therapy11 Apr 2022Cited by 11 (Europe PMC)

PMID35410439PMCIDPMC8996222DOI10.1186/s13287-022-02831-1PepBankPUB-35410439

Summary

BackgroundVarious 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.MethodsWe 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.ResultsWe 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.ConclusionOur 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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone5

In this study, Dihexa was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Dihexa.

01AnimalNot a test of Dihexa aloneAnimal study (in vivo)Efficacy outcome
In vivo, hepatocyte-like cells produced with the chemical protocol that included Dihexa repopulated injured liver.
In plain wordsIn animals, cells produced with the protocol that included Dihexa repopulated injured liver.
Peptide
Dihexa
Outcome
IncreaseInjured liver repopulation
Study
n: not reported in source
Injured liver
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
The small-molecule-derived HLCs displayed typical functional characteristics as mature hepatocytes in vitro and repopulating injured liver in vivo.
2 context sentences(design, population, supporting numbers)
Summary · context
Furthermore, we identified that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute growth factors to induce hepatic specification.
Summary · context
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.
In this study, Dihexa was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dihexa.
Show in the study text Report a problemFND-3541043905
02LabNot a test of Dihexa aloneIn vitro (cells)Activity measurement
In human pluripotent stem cells, Vitamin C, Dihexa, and Forskolin together substituted for growth factors to induce hepatic specification.
In plain wordsIn cells, Vitamin C, Dihexa, and Forskolin together replaced growth factors for hepatic specification.
Peptide
Dihexa
Outcome
IncreaseHepatic specification
Study
Humann: not reported in source
Human pluripotent stem cell-derived hepatic cells
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
Furthermore, we identified that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute growth factors to induce hepatic specification.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Dihexa was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dihexa.
Show in the study text Report a problemFND-3541043901
03LabNot a test of Dihexa aloneIn vitro (cells)Activity measurement
In human stem cell-derived hepatoblasts, the established chemical formulas supported expansion.
In plain wordsIn cells, the chemical protocol that included Dihexa supported hepatoblast expansion.
Peptide
Dihexa
Outcome
IncreaseHepatoblast expansion
Study
Humann: not reported in source
Human pluripotent stem cell-derived hepatic cells
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
The obtained hepatoblasts (HBs) could subsequently expand and mature into functional hepatocyte-like cells (HLCs) by the established chemical formulas.
2 context sentences(design, population, supporting numbers)
Summary · context
Furthermore, we identified that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute growth factors to induce hepatic specification.
Summary · context
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.
In this study, Dihexa was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dihexa.
Show in the study text Report a problemFND-3541043902
04LabNot a test of Dihexa aloneIn vitro (cells)Activity measurement
In human stem cell-derived hepatoblasts, the established chemical formulas supported maturation into functional hepatocyte-like cells.
In plain wordsIn cells, the chemical protocol that included Dihexa supported maturation into functional liver-like cells.
Peptide
Dihexa
Outcome
IncreaseHepatocyte-like cell maturation
Study
Humann: not reported in source
Human pluripotent stem cell-derived hepatic cells
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
The obtained hepatoblasts (HBs) could subsequently expand and mature into functional hepatocyte-like cells (HLCs) by the established chemical formulas.
2 context sentences(design, population, supporting numbers)
Summary · context
Furthermore, we identified that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute growth factors to induce hepatic specification.
Summary · context
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.
In this study, Dihexa was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dihexa.
Show in the study text Report a problemFND-3541043903
05LabNot a test of Dihexa aloneIn vitro (cells)Activity measurement
In vitro, hepatocyte-like cells produced with the chemical protocol that included Dihexa displayed typical mature hepatocyte functional characteristics.
In plain wordsIn lab tests, cells produced with the protocol that included Dihexa showed typical mature liver cell functions.
Peptide
Dihexa
Outcome
Not applicableMature hepatocyte functional characteristics
Study
Humann: not reported in source
Human pluripotent stem cell-derived hepatic cells
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
The small-molecule-derived HLCs displayed typical functional characteristics as mature hepatocytes in vitro and repopulating injured liver in vivo.
2 context sentences(design, population, supporting numbers)
Summary · context
Furthermore, we identified that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute growth factors to induce hepatic specification.
Summary · context
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.
In this study, Dihexa was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dihexa.
Show in the study text Report a problemFND-3541043904

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:45 UTC
First added · source update from Europe PMC

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