Human-Induced Pluripotent Stem Cell Technology: Toward the Future of Personalized Psychiatry

Abstract

The polygenic and multifactorial nature of many psychiatric disorders has hampered implementation of the personalized medicine approach in clinical practice. However, induced pluripotent stem cell (iPSC) technology has emerged as an innovative tool for patient-specific disease modeling to expand the pathophysiology knowledge and treatment perspectives in the last decade. Current technologies enable adult human somatic cell reprogramming into iPSCs to generate neural cells and direct neural cell conversion to model organisms that exhibit phenotypes close to human diseases, thereby effectively representing relevant aspects of neuropsychiatric disorders. In this regard, iPSCs reflect patient pathophysiology and pharmacological responsiveness, particularly when cultured under conditions that emulate spatial tissue organization in brain organoids. Recently, the application of iPSCs has been frequently associated with gene editing that targets the disease-causing gene to deepen the illness pathophysiology and to conduct drug screening. Moreover, gene editing has provided a unique opportunity to repair the putative causative genetic lesions in patient-derived cells. Here, we review the use of iPSC technology to model and potentially treat neuropsychiatric disorders by illustrating the key studies on a series of mental disorders, including schizophrenia, major depressive disorder, bipolar disorder, and autism spectrum disorder. Future perspectives will involve the development of organ-on-a-chip platforms that control the microenvironmental conditions so as to reflect individual pathophysiological by adjusting physiochemical parameters according to personal health data. This strategy could open new ways by which to build a disease model that considers individual variability and tailors personalized treatments.

Human‐based new approach methodologies to accelerate advances in nutrition research

“…Subsequently, patient-specific iPSCs could provide unlimited diseaserelevant cells in a personalized manner, serving as a valuable supply of previously inaccessible cell types, including cardiomyocytes (Karakikes et al, 2015), neurons (Alciati et al, 2022), intestinal (Grouls et al, 2022;Yoshida et al, 2021), hepatic (Inoue et al, 2020;Vallverdú et al, 2021) and pancreatic cells (Balboa et al, 2021;Choi et al, 2021;Genova et al, 2021). intestinal tissues where microbiota-produced butyrate is a significant energy source (Grouls et al, 2022).…”

“…This enables the collection of source material from both healthy individuals and patients, allowing the study and the comparison between different genetic backgrounds. Subsequently, patient‐specific iPSCs could provide unlimited disease‐relevant cells in a personalized manner, serving as a valuable supply of previously inaccessible cell types, including cardiomyocytes (Karakikes et al., 2015), neurons (Alciati et al., 2022), intestinal (Grouls et al., 2022; Yoshida et al., 2021), hepatic (Inoue et al., 2020; Vallverdú et al., 2021) and pancreatic cells (Balboa et al., 2021; Choi et al., 2021; Genova et al., 2021).…”

Human iPSCs from aged donors retain their mitochondrial aging signature

“…The inaccessibility of live human brain samples, such as neurons, has slowed progress in this area. Induced pluripotent stem cells (iPSCs) represent synthetic stem cells that are “reprogrammed” or induced from somatic cells cultured with various transcription factors like Klf4,c-Myc, Oct4 and Sox2 (Alciati, Reggiani et al 2022). The first human iPSCs were created from a skin biopsy of skin fibroblasts (Abdullah, Pollock et al 2012).…”

Evaluation of Human-Induced Pluripotent Stem Cells Derived from a Patient with Schwartz–Jampel Syndrome Revealed Distinct Hyperexcitability in the Skeletal Muscles

“…Since the establishment of human-induced pluripotent stem cells (hiPSCs) in 2007 [ 12 ], disease organ models have been constructed using hiPSCs derived from patients with genetic diseases to elucidate pathological mechanisms [ 13 , 14 ]. Compared to mouse models, which have been mainly used to analyze pathological conditions, in vitro hiPSC models are more likely to reflect the pathological conditions without the differences in species between humans and mice.…”