Lo Wen-Jyi, Lin Chiao-Lin, Chang Yu-Chien, Bai Li-Yuan, Lin Chen-Yuan, Liang Ji-An, Li Long-Yuan, Chao Ling-Min, Chiu Chang-Fang, Chen Chuan-Mu, Yeh Su-Peng
Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Ann Hematol. 2018 Apr;97(4):697-707. doi: 10.1007/s00277-018-3231-y. Epub 2018 Jan 18.
Total body irradiation (TBI) is frequently used in hematopoietic stem cell transplantation (HSCT) and is associated with many complications due to radiation injury to the normal cells, including normal stem cells. Nevertheless, the effects of TBI on the mesenchymal stromal stem cell (MSC) are not fully understood. Bone marrow-derived MSCs (BM-MSCs) isolated from normal adults were irradiated with 200 cGy twice daily for consecutive 3 days, a regimen identical to that used in TBI-conditioning HSCT. The characteristics, differentiation potential, cytogenetics, hematopoiesis-supporting function, and carcinogenicity of the irradiated BM-MSCs were then compared to the non-irradiated control. The irradiated and non-irradiated MSCs shared similar morphology, phenotype, and hematopoiesis-supporting function. However, irradiated MSCs showed much lower proliferative and differentiative potential. Irradiation also induced clonal cytogenetic abnormalities of MSCs. Nevertheless, the carcinogenicity of irradiated MSCs is low in vitro and in vivo. In parallel with the ex vivo irradiation experiments, decreased proliferative and differentiative abilities and clonal cytogenetic abnormalities can also be found in MSCs isolated from transplant recipients who had received TBI-based conditioning previously. Thus, TBI used in HSCT drastically injury MSCs and may contribute to the development of some long-term complications associated with clonal cytogenetic abnormality and poor adipogenesis and osteogenesis after TBI.
全身照射（TBI）常用于造血干细胞移植（HSCT），由于其对包括正常干细胞在内的正常细胞造成辐射损伤，会引发多种并发症。然而，TBI对间充质基质干细胞（MSC）的影响尚未完全明确。从正常成年人中分离出的骨髓源性MSC（BM-MSC），每天接受两次200 cGy的照射，连续照射3天，该方案与TBI预处理HSCT中使用的方案相同。然后将照射后的BM-MSC的特征、分化潜能、细胞遗传学、造血支持功能和致癌性与未照射的对照组进行比较。照射后的和未照射的MSC具有相似的形态、表型和造血支持功能。然而，照射后的MSC显示出低得多的增殖和分化潜能。照射还诱导了MSC的克隆细胞遗传学异常。尽管如此，照射后的MSC在体外和体内的致癌性都很低。与体外照射实验同时，在先前接受过基于TBI预处理的移植受者分离出的MSC中，也能发现增殖和分化能力下降以及克隆细胞遗传学异常。因此，HSCT中使用的TBI会严重损伤MSC，并可能导致一些与克隆细胞遗传学异常以及TBI后脂肪生成和骨生成不良相关的长期并发症的发生。
