Correspondence to “Bipolar disorder-iPSC derived neural progenitor cells exhibit dysregulation of store-operated Ca²⁺ entry and accelerated differentiation” by Hewitt et al. (PMID: 37402854)

An increasing interest in patient-specific disease modeling of neuropsychiatric disorders with multifactorial etiology has been witnessed by researchers worldwide [1]. Bipolar disorder (BD) is a complex neuropsychiatric disorder with high heritability rates that could benefit from the use of patient-specific cell lines to study molecular mechanisms [2]. We therefore read with interest the work of Hewitt and colleagues (2023), which investigated aspects of BD pathophysiology and more specifically calcium-related mechanisms, using induced pluripotent stem cells (iPSC)-derived neurons. However, we noted that some aspects of the study could be further clarified, which would facilitate the interpretation of these findings for the wider clinical and non-clinical scientific community interested in this field. For example, the absence of information regarding quality control (QC) in some of the generated iPSC lines, clinical details, repository information, and methodological details.

The current study from Hewitt and colleagues (Suppl. Fig. S1 A) examined three patients and three controls (one clone each) [3]. However, it is concerning that neither the current study [3] nor the linked work by Zimmermann et al. [4] and Bavamian et al. [5] appeared to clearly provide and/or describe QC information for all the iPSCs that were produced [6]. Good Cell Culture Practices outlined by the International Society for Stem Cell Research highlights the need for structured iPSC generation and reporting, to enable information interchange and biological characterization of cell lines in a reproducible manner [7]. One of the international registries for pluripotent stem cells is the hPSCReg, which is free of charge and contains data about multiple cell lines generated by researchers around the world [8]. This possibility helps with the dissemination of trustworthy, reproducible information about newly generated iPSCs amongst the iPSC community. Using these cells for the examination of complex neuropsychiatric disorders is powerful, as the presence of numerous sporadic cases can be attributed to polygenic factors with individually small impact magnitudes, rather than solely to the impact of environmental factors or new mutations with larger effect sizes [9]. Therefore, it is crucial to thoroughly analyze clinical and polygenic data from the donors in order to assess the impact of environmental and genetic factors on the etiology of these disorders in sporadic cases [6]. Unfortunately, the article lacked the aforementioned data.