辐射对 C3H10T1/2 间充质干细胞系的影响：白血病细胞调控中旁观者效应的体外挑战

Mesenchymal stem cells (MSCs) in the bone marrow (BM) stroma modulate hematopoiesis through paracrine signaling. In leukemia, the BM stroma can be reprogrammed, affecting normal hematopoiesis. Radiation therapy, a common treatment for hematological malignancies, impacts not only directly irradiated cells but also nearby non-irradiated cells through the radiation-induced bystander effect (RIBE).

This phenomenon occurs when non-irradiated cells exhibit radiation damage due to signals from nearby irradiated cells, which undergo changes through communication with irradiated neighbors, primarily via paracrine signaling. This challenges the traditional view that radiation damage is confined to directly irradiated cells.

However, how this phenomenon modulates MSCs and its specific effects on leukemic cells remain unclear. MSCs were irradiated with doses of 4, 6, and 15Gy, and their secretome was analyzed to understand how these factors influence leukemia cells. The results showed that doses higher than 6Gy significantly affected MSC viability, apoptosis, and cell cycle distribution, with 6Gy chosen for further RIBE analysis due to its balance between cellular damage and viability.

Clonogenic assays revealed that leukemic cells cultured with 6Gy-conditioned media showed reduced colony formation and metabolic activity. Although cell viability was unaffected, RIBE altered the cell cycle in G-CSF-stimulated leukemic cells, decreasing Ccnd1 expression and increasing Cdkn1a expression. Gata3 expression was also reduced. Flow cytometry revealed insignificant changes in surface markers, except for CD3e in G-CSF-stimulated cells.

These findings provide new insights into how radiation-induced bystander effects alter the behavior of leukemic cells, prompting further research into RIBE's implications for cancer therapy.