As a leading service provider in the field of cell reprogramming, Creative Bioarray is committed to helping clients generate iPSC-derived hepatocytes for hepatotoxicity assessment. Our specialized solutions offer the possibility to study the role of genetic diversity in patients who show specific responses to drugs.
Introduction
Drug hepatotoxicity, which causes liver injury and acute liver failure, is a growing public health problem and a major challenge in clinical drug development. Drug-induced hepatotoxicity involves multiple mechanisms, including cholestasis, steatosis, production of reactive intermediates, and oxidative stress. The development of highly predictive assays for efficacy and safety testing is critical to improve drug development and reduce drug attrition.
Primary human hepatocytes are metabolically and functionally competent and represent the closest in vitro model to the human liver, but the difficulty of obtaining them and the significant intrinsic and phenotypic variability they exhibit limit their use in predictive hepatotoxicity studies. Recently, some studies have proposed that hiPSC-derived hepatocytes show the typical characteristics and metabolism of mature cells, and are expected to be used as physiological substitutes for primary human hepatocytes for high-content screening in early drug development.
Fig.1 Hepatotoxicity assay of hepatocyte-like cells derived from iPSCs from rheumatoid arthritis patients with hepatotoxicity. (Kim, 2018)
Solutions for Hepatotoxicity Assessment based on Cell Reprogramming
To help researchers improve drug development and reduce drug attrition, Creative Bioarray has worked to develop and optimize methods for the formation of 3D liver spheroids derived from hiPSC, as well as confocal imaging and analytical approaches for hepatotoxicity assessment. In addition, we help clients measure multiple hepatotoxicity phenotypes such as mitochondrial membrane potential decline, reactive oxygen species production and plasma membrane rupture in a single assay. The solutions we offer include:
- Hepatosphere formation using human iPSC-derived hepatocytes.
- Assessment of hepatotoxicity using 3D models for in vitro screening.
- High-throughput 3D image acquisition and analysis.
- Assess toxicity using multi-parametric phenotypic screens, including observation of changes in spheroid phenotype and cell content, as well as assessment of apoptotic phenotype and mitochondrial integrity.
Applications
- Study on idiosyncratic hepatotoxicity
- Research on diverse CYP profiles in the human population
- Disease phenotype research for identifying new therapeutic targets
- Retrospective clinical studies
With a best-in-class experimental platform and dedicated technical staff, Creative Bioarray is committed to helping customers generate hiPSC-derived hepatocytes to develop sensitive and reproducible screening tools for the assessment of hepatotoxicity. We offer flexible and professional solutions to help you shorten your time to quickly analyze hepatotoxicity and ultimately provide you with a complete analytical report. If you need services in hepatotoxicity testing, please feel free to contact us.
Reference
- Kim, J.; et al. Recapitulation of methotrexate hepatotoxicity with induced pluripotent stem cell-derived hepatocytes from patients with rheumatoid arthritis. Stem cell research & therapy. 2018, 9(1): 1-15.