Fujishiro Aya, Miura Yasuo, Iwasa Masaki, Fujii Sumie, Sugino Noriko, Andoh Akira, Hirai Hideyo, Maekawa Taira, Ichinohe Tatsuo
Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507 Japan.
Division of Gastroenterology and Hematology, Department of Medicine, Shiga University of Medical Science, Setatsukinowacho, Otsu, Shiga 520-2192 Japan.
Inflamm Regen. 2017 Sep 1;37:19. doi: 10.1186/s41232-017-0049-2. eCollection 2017.
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).
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.
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 CD34CD38 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 CD34CD38 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.
Our results suggest that acute exposure to low-dose (0.1 Gy) radiation can transiently affect the functional characteristics of human BM-MSCs.
近年来，低剂量辐射对人类健康的影响受到越来越多的关注。我们研究了低剂量辐射是否会影响源自骨髓（BM）的间充质基质/干细胞（MSC）的功能，MSC是组织/器官支持性干细胞。
本研究使用了来自五名健康个体的正常人BM-MSC。将培养扩增的BM-MSC以0.8 Gy/min的速率暴露于0.1戈瑞（Gy）的γ射线（铯-137）（辐照后的MSC，Ir-MSC），并研究其扩增、多向分化和造血支持能力。
在五批中的两批中，与未辐照的BM-MSC（非辐照的MSC，non-Ir-MSC）相比，低剂量γ射线辐照后BM-MSC的扩增暂时延迟。尽管有一批BM-MSC的分化倾向于暂时降低，但低剂量辐照对成脂和成骨分化能力没有显著影响。当人BM造血干/祖细胞（HPC）与Ir-MSC共培养时，在五批中的两批中，与非辐照的MSC共培养相比，HPC产生CD34CD38细胞的能力增强。在受影响的Ir-MSC批次中，白细胞介素（IL）-6的mRNA表达水平升高，干细胞因子（SCF）和fms相关酪氨酸激酶3配体（Flt3L）的mRNA表达水平降低。在另外三批BM-MSC中，未观察到细胞生长延迟、共培养时HPC产生CD34CD38细胞的能力增强以及IL-6表达增加和SCF及Flt3L表达降低的组合。值得注意的是，经过3周培养后，这些受影响的Ir-MSC的特性恢复到与非辐照的MSC相似的水平。
我们的结果表明，急性暴露于低剂量（0.1 Gy）辐射可暂时影响人BM-MSC的功能特性。
