Chang Yu-Hsun, Liu Hwan-Wun, Chu Tang-Yuan, Wen Yao-Tseng, Tsai Rong-Kung, Ding Dah-Ching
Cell Transplant. 2017 Jun 9;26(6):1077-1087. doi: 10.3727/096368917X694886. Epub 2017 Feb 3.
Adipose tissue-derived mesenchymal stem cells (ADSCs) are derived from adipose tissue and can be induced in vitro to differentiate into osteoblasts, chondroblasts, myocytes, neurons, and other cell types. Cisplatin is a commonly used chemotherapy drug for cancer patients. However, the effects of cisplatin on ADSCs remain elusive. This study found that a high concentration of cisplatin affects the viability of ADSCs. First, the IC50 concentration of cisplatin was evaluated. Proliferation of ADSCs, as assessed by the XTT method, decreased immediately after treatment with various concentrations of cisplatin. ADSCs maintained mesenchymal stem cell surface markers after cisplatin treatment, as determined by flow cytometry. Upon differentiation by adding specific reagents, a significant decrease in adipogenic differentiation (by Oil red O staining) and osteogenic differentiation (by Alizarin red staining), and significant chondrogenic differentiation (by Alcian blue staining) were found after cisplatin treatment. Quantitative RT-PCR was also used in evaluating expression of specific genes to confirm differentiation. Finally, ADSCs from one donor who had received cisplatin showed significantly decreased adipogenic differentiation but increased osteogenic differentiation compared with ADSCs derived from one healthy donor. In conclusion, cisplatin affects the viability, proliferation, and differentiation of ADSCs both in vitro and in vivo via certain signaling pathways, such as p53 and Fas/FasL. The differentiation abilities of ADSCs should be evaluated before their transplantation for repairing cisplatin-induced tissue damage.
脂肪组织来源的间充质干细胞(ADSCs)源自脂肪组织,可在体外诱导分化为成骨细胞、软骨细胞、肌细胞、神经元和其他细胞类型。顺铂是癌症患者常用的化疗药物。然而,顺铂对ADSCs的影响仍不清楚。本研究发现高浓度顺铂会影响ADSCs的活力。首先,评估了顺铂的IC50浓度。用XTT法评估,ADSCs的增殖在使用各种浓度顺铂处理后立即下降。通过流式细胞术测定,顺铂处理后的ADSCs保持间充质干细胞表面标志物。在用特定试剂诱导分化后,发现顺铂处理后脂肪生成分化(通过油红O染色)、成骨分化(通过茜素红染色)显著降低,软骨生成分化(通过阿尔辛蓝染色)也显著降低。定量RT-PCR也用于评估特定基因的表达以确认分化。最后,与来自一名健康供体的ADSCs相比,来自一名接受过顺铂治疗的供体的ADSCs脂肪生成分化显著降低,但成骨分化增加。总之,顺铂通过某些信号通路,如p53和Fas/FasL,在体外和体内影响ADSCs的活力、增殖和分化。在将ADSCs用于修复顺铂诱导的组织损伤之前,应评估其分化能力。