Applications and Limitations of the Use of hiPSCs in Pharmacological Research

The controversies surrounding animal experimentation, its application in pharmacological research has contributed immensely to drug discovery. The fact that most animal models share similar molecular targets with humans makes them essential regulatory requirements for pre-clinical pharmacology experiments for new drugs. Consequently, millions of experimental animals have been used globally. However, with the introduction of the replacement, reduction and refinement (3Rs) ethical framework to reduce experimental animal use and their suffering, investigators are required to adhere to their principles. Although in vitro models have been proposed as alternatives to animal models, there are limitations to their use, especially those related to pharmacokinetics under culture conditions. The use of stem cells, including induced pluripotent stem cells (iPSCs) reprogrammed from adult somatic cells, have been proposed as viable and reliable alternatives to animal experimentation and in vitro modelling because they can be reprogrammed into various cells for application in pharmacological research. In this respect, human induced pluripotent stem cells (hiPSCs) can be generated from patients with specific diseases, allowing the creation of in vitro disease models that mimic the cellular and molecular characteristics of the relevant disease. hiPSC-derived cells can also be employed in screening new drug candidates for efficacy and toxicity, thus allowing for personalised drug screening, and identifying drugs that are most likely to be effective and safe for a specific patient. Furthermore, hiPSCs have potential applications in identifying and validating potential drug targets by studying the cellular and molecular mechanisms underlying disease. However, despite promising applications of hiPSCs, there are challenges in ensuring the quality, safety, and reproducibility of hiPSC-derived cells, as well as in accurately modelling complex diseases and predicting long-term drug effects. Also, there are still ethical considerations related to the source of somatic cells used for re-programming. The lecture will throw more light on successful applications of hiPSCs in pharmacological research, as well as challenges with the use of iPSCs as alternatives to animal and in vitro experiments.