Promising Developments in the Use of Induced Pluripotent Stem Cells in Research of ADHD

Abstract

Although research using animal models, peripheral and clinical biomarkers, multimodal neuroimaging techniques and (epi)genetic information has advanced our understanding of attention-deficit/hyperactivity disorder (ADHD), the etiopathology of this neurodevelopmental disorder has still not been elucidated. Moreover, as the primary affected tissue is the brain, access to samples is problematic. Alternative models are therefore required, facilitating cellular and molecular analysis. Recent developments in stem cell research have introduced the possibility to reprogram somatic cells from patients, in this case ADHD, and healthy controls back into their pluripotent state, meaning that they can then be differentiated into any cell or tissue type. The potential to translate patients' somatic cells into stem cells, and thereafter to use 2-and 3-dimensional (2D and 3D) neuronal cells to model neurodevelopmental disorders and/or test novel drug therapeutics, is discussed in this chapter. Keywords Attention-deficit disorder (ADD) • Attention-deficit/hyperactivity disorder (ADHD) • cell models • induced pluripotent stem cells (iPSC) • neuronal cells • personalized modelling Abbreviations ADD Attention-deficit disorder ADHD Attention-deficit/hyperactivity disorder ASD Autism spectrum disorder BDNF Brain-derived neurotrophic factor CRISPR-cas9 Clustered Regularly Interspaced Short Palindromic Repeats-D/CRISPRassociated protein 9 CSF Cerebrospinal fluid CNS Central nervous system CNV Copy number variants 2D /3D Two / three dimension(al) DNA Deoxyribonucleic acid fMRI Functional magnetic resonance imaging GLUT3 Glucose transporter-3 (SCL2A3) GSK3-β Glycogen synthase kinase 3-β GWAS Genome-wide association study (studies) iPSC Induced pluripotent stem cell

Growth rates of human induced pluripotent stem cells and neural stem cells from attention-deficit hyperactivity disorder patients: a preliminary study

“…Therefore, it is of importance to recreate the disorder in an accurate model that recapitulates the genetic background of individuals (Green et al 2022 ; Faraone and Larsson 2019 ). Induced pluripotent stem cell (iPSC) technology displays a relevant tissue model, as cell reprogramming can be conducted on non-invasively obtained somatic cells from patients (Wiegand and Banerjee 2019 ; Yde Ohki et al 2022 ). Human iPSCs allows the research of different developmental stages from iPSCs to mature neurons, mimicking embryonic neurogenesis (Compagnucci et al 2014 ).…”