Neuroprotective Effects of Human Adipose Tissue-Derived Mesenchymal Stromal Cells Against Radiation-Induced Neural Damage : A Comparative In Vitro Study.

Abstract

Objective: Radiotherapy is a key treatment for brain tumors and arteriovenous malformations; however, it is associated with adverse effects such as brain edema, demyelination, and delayed necrosis. These adverse effects are driven by inflammation and apoptosis, initiated by cytokines such as tumor necrosis factor-α, transforming growth factor, and interleukin-1β. Adipose tissuederived mesenchymal stromal cells (ADMSCs) offer protection against radiation-induced damage owing to their pluripotency and antiinflammatory properties. In this study, we investigated the neuroprotective effects of ADMSCs on irradiated brain cells.

Methods: Rat cortical neurons, human glioblastoma cells (U87 cell line), and ADMSCs were exposed to radiation doses ranging from 3 Gy to 40 Gy. Co-cultures of irradiated neurons with ADMSCs or their secretomes were assessed for apoptotic and inflammatory markers. Cell viability was measured using lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Apoptosis was determined by using Hoechst staining and western blot analysis of proteins such as Bax, caspase-3, and Bcl-2.

Results: Higher radiation doses (30-40 Gy) significantly increased apoptosis and decreased the viability of cortical neurons and U87 cells. Co-culture with ADMSCs reduced the levels of apoptosis markers, particularly Bax and cleaved caspase-3, and promoted cell survival. Direct co-culture provided more pronounced protection than did ADMSC secretome treatment, suggesting that cell-to-cell interactions are crucial for neuroprotection.

Conclusion: ADMSCs have a significant potential for mitigating radiation-induced brain damage by reducing apoptosis and inflammation. Direct ADMSC co-culture outperformed secretome treatment, thereby emphasizing the importance of physical cell interactions. ADMSC therapy may be a promising approach to protect against radiotherapy-induced neural damage. Further studies are required to optimize the delivery and timing of stem cell therapy.