3D stem cell-derived liver organoids
Research has shown that unique African genetic variants in hepatic metabolism genes alter the efficiency of drug metabolism, and thus drug response. For example, CYP2D6, an important enzyme from the Cytochrome P450 superfamily for drug metabolism, assists in the formation of endoxifen from tamoxifen in breast cancer, and metabolism of primaquine to 5-hydroxyprimaquine in malaria and pneumocystis pneumonia.
The African-specific CYP2D6*17 allele causes a reduced function effect on the CYP2D6 enzyme and decreases substrate affinity, thus negating pharmaceutical benefits for a portion of African patients. Numerous methods have been employed to study such effects in a physiologically relevant in vitro model. Primary human hepatocytes for example are the current gold standard but are expensive, and difficult to maintain for long periods in culture.
Cancer derived cell lines such as HepG2s are chromosomally inaccurate and lack the maturity required for physiologically relevant metabolism. In the CSIR Bioengineering and integrated genomics research group researchers have developed an induced pluripotent stem cell derived 3D liver model.
This inexpensive model can be genetically engineered to compare the effect of African genetic variants with classically European screening trials on frequently prescribed pharmaceutically compounds used in treating high-impact diseases in South Africa.
Dr Janine Scholefield