The use of induced pluripotent stem cells (iPSCs) represents one of the most promising frontiers in contemporary translational neuroscience. Derived from somatic cells, such as skin fibroblasts, iPSCs are genetically reprogrammed to a pluripotent state, acquiring the ability to differentiate into multiple cell types, including neurons. This technology allows the precise modeling of neuropsychiatric disorders, such as schizophrenia and bipolar disorder, within a patient-specific genetic context, which enables a new generation of biomolecular and pharmacological studies aimed at personalized medicine (Rodrigues et al., 2024).
Understanding the etiopathogenesis of mental disorders has been profoundly benefited by the application of iPSCs. Among the pathophysiological mechanisms elucidated with the aid of this technology, oligodendrogenesis stands out — the process of differentiation of oligodendrocytes, cells responsible for the myelination of axons. Dysfunctions in this process have been associated with cognitive and social impairments, frequently observed in severe psychiatric conditions. The presence of alterations in intracellular calcium signaling, essential for the proliferation and differentiation of neural and glial progenitors, is also relevant. These phenomena have been repeatedly described as potential therapeutic targets, given their contribution to synaptic plasticity and the global functioning of neural circuits (Rodrigues et al., 2024).
In addition to their applicability in elucidating the cellular and molecular mechanisms of mental disorders, iPSCs enable the creation of in vitro platforms for screening pharmacological compounds, reducing dependence on animal models and increasing translational fidelity. Studies using cell lines derived from patients with different genetic profiles and clinical histories allow testing the efficacy and safety of drugs in a personalized manner, anticipating individual responses to treatment. However, this potential still faces considerable technical challenges, such as phenotypic variability between iPSC lines, the difficulty in replicating the neural microenvironment in vivo, and the complexity of functional maturation of neurons in culture (Rodrigues et al., 2024).
In clinical terms, the direct therapeutic application of iPSCs still faces critical barriers. The possibility of tumorigenicity associated with incompletely differentiated cells, immunological risks, and logistical difficulties related to the transport, storage, and traceability of cells are issues that have not yet been fully resolved. Furthermore, cell therapies require standardized and rigorous protocols to ensure safety and efficacy, especially in clinical trials aimed at vulnerable populations, such as critically ill psychiatric patients. Overcoming these obstacles depends on a coordinated effort between neuroscientists, cell biologists, psychiatrists, and biomedical engineers (Rodrigues et al., 2024).
In summary, the application of iPSCs in the field of mental disorders represents a paradigmatic milestone at the intersection of genetics, cell biology and psychiatry. The possibility of studying the biology of the human brain in personalized models in the laboratory opens an unprecedented window for understanding and intervening in psychiatric diseases. Although there is still a long way to go until this technology is fully integrated into clinical practice, the advances already achieved point to a future in which personalized, mechanism-based therapy may become a concrete reality.
Reference:
RODRIGUES, Fabiano de Abreu Agrela; CARVALHO, Luiz Felipe; NASCIMENTO, Flávio Henrique dos Santos; KOSTIC, Velibor. Treatment of mental disorders with stem cells: a promising area in evolution. Cognitio, v. 7, n. 1, p. 268-276, 2024. DOI: 10.38087/2595.8801.427.
