Effects of acute exposure to low-dose radiation on the characteristics of human bone marrow mesenchymal stromal/stem cells

低剂量急性辐射对人骨髓间充质基质细胞/干细胞特性的影响

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作者:Aya Fujishiro, Yasuo Miura, Masaki Iwasa, Sumie Fujii, Noriko Sugino, Akira Andoh, Hideyo Hirai, Taira Maekawa, Tatsuo Ichinohe

Background

In recent years, increasing attention has been paid to the effects of low-dose irradiation on human health. We examined whether low-dose irradiation affected the functions of mesenchymal stromal/stem cells (MSCs), which are tissue/organ-supportive stem cells, derived from bone marrow (BM).

Conclusions

Our results suggest that acute exposure to low-dose (0.1 Gy) radiation can transiently affect the functional characteristics of human BM-MSCs.

Methods

Normal human BM-MSCs from five healthy individuals were used in this study. Culture-expanded BM-MSCs were exposed to 0.1 gray (Gy) of γ-radiation (Cesium-137) at a rate of 0.8 Gy/min (Ir-MSCs), and their expansion, multi-differentiation, and hematopoiesis-supportive capabilities were investigated.

Results

The expansion of BM-MSCs was transiently delayed after low-dose γ-irradiation compared with that of non-irradiated BM-MSCs (non-Ir-MSCs) in two out of five lots. Adipogenic and osteogenic differentiation capabilities were not significantly affected by low-dose irradiation, although one lot of BM-MSCs tended to have transiently reduced differentiation. When human BM hematopoietic stem/progenitor cells (HPCs) were co-cultured with Ir-MSCs, the generation of CD34+CD38+ cells from HPCs was enhanced compared with that in co-cultures with non-Ir-MSCs in two out of five lots. The mRNA expression level of interleukin (IL)-6 was increased and those of stem cell factor (SCF) and fms-related tyrosine kinase 3 ligand (Flt3L) were decreased in the affected lots of Ir-MSCs. In the other three lots of BM-MSCs, a cell growth delay, enhanced generation of CD34+CD38+ cells from HPCs in co-culture, and a combination of increased expression of IL-6 and decreased expression of SCF and Flt3L were not observed. Of note, the characteristics of these affected Ir-MSCs recovered to a similar level as those of non-Ir-MSCs following culture for 3 weeks. Conclusions: Our results suggest that acute exposure to low-dose (0.1 Gy) radiation can transiently affect the functional characteristics of human BM-MSCs.

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