Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaque accumulation and neuroinflammation. Mesenchymal Stromal Cells (MSCs) have emerged as a promising therapeutic tool due to their potent immunomodulatory and neurotrophic properties. This study investigated the mutual influence and mechanisms of interaction between multipotent MSCs and primary hippocampal cell cultures derived from 5XFAD transgenic mice, a model for familial AD. The primary objective was to compare the efficacy of direct and indirect cocultivation methods in mitigating AD-related pathology. Using immunocytochemistry and biochemical assays, we analyzed neuronal survival, Aβ load, and synaptic marker expression. Our findings indicate that the cocultivation method significantly influences the protective effects of MSCs. Specifically, direct contact was shown to enhance neuronal viability and reduce Aβ accumulation more effectively than indirect methods, suggesting a critical role for cell-to-cell communication, potentially via gap junctions, in the therapeutic mechanism. This work highlights the importance of optimizing cell delivery strategies for MSC-based therapies and provides a foundation for future in vivo studies targeting neurodegenerative diseases.