Recommendations, guidelines, and best practice for the use of human induced pluripotent stem cells for neuropharmacological studies of neuropsychiatric disorders
Lucia Dutan Polit, Ilse Eidhof, Rhiannon V. McNeill, Katherine Warre‐Cornish, Cristine Marie Yde Ohki, Natalie Monet Walter, Carlo Sala, Chiara Verpelli, Franziska Radtke, Silvana Galderisi, Armida Mucci, Ginetta Collo, Frank Edenhofer, Maija L. Castrén, János Réthelyi, Morten Ejlersen, Sonja Hohmann, Mirolyuba Ilieva, Renāte Lukjanska, Rugilė Matulevičiūtė, Tanja Maria Michel, Femke M.S. de Vrij, Steven A. Kushner, Bas Lendemeijer, Sarah Kittel‐Schneider, Georg Ziegler, Doris Gruber-Schoffnegger, R. Jeroen Pasterkamp, Amal Kasri, Marie‐Claude Potier, Juergen A. Knoblich, Oliver Brüstle, Michael Peitz, Emilio Merlo Pich, Adrian J. Harwood, Elsa Abranches, Anna Falk, Anthony C. Vernon, Edna Grünblatt, Deepak P. Srivastava
Abstract
The number of individuals suffering from neuropsychiatric disorders (NPDs) has increased worldwide, with 3 million disability-adjusted life-years calculated in 2019. Though research using various approaches including genetics, imaging, clinical and animal models has advanced our knowledge regarding NPDs, we still lack basic knowledge regarding the underlying pathophysiological mechanisms. Moreover, there is an urgent need for highly effective therapeutics for NPDs. Human induced pluripotent stem cells (hiPSCs) generated from somatic cells enabled scientists to create brain cells in a patient-specific manner. However, there are challenges to the use of hiPSCs that need to be addressed. In the current paper, consideration of best practices for neuropharmacological and neuropsychiatric research using hiPSCs will be discussed. Specifically, we provide recommendations for best practice in patient recruitment, including collecting demographic, clinical, medical (before and after treatment and response), diagnostic (including scales) and genetic data from the donors. We highlight considerations regarding donor genetics and sex, in addition to discussing biological and technical replicates. Furthermore, we present our views on selecting control groups/lines, experimental designs, and considerations for conducting neuropharmacological studies using hiPSC-based models in the context of NPDs. In doing so, we explore key issues in the field concerning reproducibility, statistical analysis, and how to translate in vitro studies into clinically relevant observations. The aim of this article is to provide a key resource for hiPSC researchers to perform robust and reproducible neuropharmacological studies, with the ultimate aim of improving identification and clinical translation of novel therapeutic drugs for NPDs.