Identification of small molecules for human hepatocyte expansion and iPS differentiation
Open accessAbstract
Cell-based therapies hold the potential to alleviate the growing burden of liver diseases. Such therapies require human hepatocytes, which, within the stromal context of the liver, are capable of many rounds of replication. However, this ability is lost ex vivo, and human hepatocyte sourcing has limited many fields of research for decades. Here we developed a high-throughput screening platform for primary human hepatocytes to identify small molecules in two different classes that can be used to generate renewable sources of functional human hepatocytes. The first class induced functional proliferation of primary human hepatocytes in vitro. The second class enhanced hepatocyte functions and promoted the differentiation of induced pluripotent stem cell-derived hepatocytes toward a more mature phenotype than what was previously obtainable. The identification of these small molecules can help address a major challenge affecting many facets of liver research and may lead to the development of new therapeutics for liver diseases.
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Patient-specific hepatocytes derived from autologous iPSCs have recently emerged as an attractive alternative that can overcome issues with primary hepatocytes.
“Patient-specific hepatocytes derived from autologous iPSCs have recently emerged as an attractive alternative that can overcome these issues [60].”
From A liver-on-a-chip platform with bioprinted hepatic spheroids (2016) · cites this paper as [60]
The paper describes stem cells as an attractive alternative to primary hepatocytes and says iPS cells offer the possibility of patient-specific hepatocyte-like cells (opening passage, page unavailable). It does not establish that these cells overcome the issues with primary hepatocytes: the same passage says their immature phenotype and limited function restrict their use as a renewable source of functional hepatocytes. (LLM, conf=0.84)
Experimental — accuracy not yet measuredHigh-throughput screening identified small molecules that supported HHs for one week with about 10-fold expansion.
“Another study using high-throughput screening identified small molecules that supported HHs for one week with about 10-fold expansion (Shan et al., 2013”
From In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity (2018) · cites this paper as Shan et al., 2013
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References 47 · Cited by 254
- Authors
- Shan, J., Schwartz, R. E., Ross, N. T., Logan, D. J., Thomas, D., Duncan, S. A., North, T. E., Goessling, W., Carpenter, A. E., & Bhatia, S. N.
- Affiliations
- Harvard–MIT Division of Health Sciences and Technology (US)
- Brigham and Women's Hospital (US)
- Broad Institute (US)
- Medical College of Wisconsin (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Bhatia, Sangeeta N
- ORCID
- Venue
- Nature Chemical Biology
- Published
- 2013-06-02
- Volume
- 9
- Issue
- 8
- Pages
- 514-520
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC3720805
- OpenAlex
- W1534392087
- Cited by
- 254
- References
- 47
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 9 · 2023: 6 · 2022: 18 · 2021: 17 · 2020: 16 · 2019: 30 · 2018: 25 · 2017: 22 · 2016: 33 · 2015: 27 · 2014: 26 · 2013: 8
- FWCI
- 19.54
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- PMC
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (HL094857, R01HL094857)
- National Human Genome Research Institute (U01HG006398, HG006398)
- National Cancer Institute (P30CA014051)
- National Institute of General Medical Sciences (R01GM089652, R01 GM0896)
- National Institute of Diabetes and Digestive and Kidney Diseases (R03DK085445, R01 DK56966, R01DK090311, R01DK085713, DK 55743, DK085445, R01DK056966, R01DK055743, DK087377, R01DK098241, RC1DK087377, R01DK065152)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- human hepatocytes, hepatocyte expansion, induced pluripotent stem cells, hepatocyte differentiation, small molecules, high-throughput compound screening, machine learning, hepatocyte proliferation, hepatocyte maturation, cell therapy, liver disease
- MeSH terms
- Cell Differentiation, Dose-Response Relationship, Drug, Humans, Structure-Activity Relationship, Molecular Structure, Hepatocytes, Cell Proliferation, Small Molecule Libraries, Induced Pluripotent Stem Cells, High-Throughput Screening Assays
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