Introduction: Neurological diseases pose significant challenges due to their complex pathophysiology and limited treatment options. Traditional models often fail to capture the intricacies of human disease. Endogenous pluripotent stem cells, derived from somatic tissues, present a promising alternative for modeling these conditions. This article reviews recent advancements in ePSC technology and its application in studying various neurological disorders, including Alzheimer's disease and Parkinson's disease.
Methods: Cell Line Development: Endogenous pluripotent stem cells (ePSCs) were derived from somatic tissues of patients diagnosed with various neurological disorders. The reprogramming process involved using non-integrative methods to minimize genomic alterations.
2. Differentiation Protocols: ePSCs were differentiated into neural progenitor cells and subsequently into specific neuronal subtypes using defined growth factors and culture conditions tailored for each lineage.
3. Characterization: The differentiated cells were characterized using:
- Immunocytochemistry: To assess the expression of neural markers (e.g., βIII-tubulin, MAP2).
- Gene Expression Analysis: Quantitative PCR was performed to evaluate the expression levels of genes associated with neurological diseases.
Functional Assays: Electrophysiological recordings and calcium imaging were conducted to assess neuronal functionality.
Results: Key findings reveal that ePSCs can differentiate into various neural lineages and exhibit disease-relevant characteristics. For instance, ePSC-derived neurons from Alzheimer's patients showed increased amyloid-beta accumulation, while those from Parkinson's patients displayed impaired mitochondrial function. These results underscore the validity of ePSCs as a tool for studying the underlying mechanisms of neurological diseases
Conclusion: Endogenous pluripotent stem cells represent a powerful resource for modeling neurological diseases, offering insights into their pathogenesis and potential therapeutic interventions. Future research should focus on refining ePSC technologies and expanding their applications to a broader range of neurological disorders.