In Vitro Effect of Carboplatin, Cytarabine, Paclitaxel, Vincristine, and Low-Power Laser Irradiation on Murine Mesenchymal Stem Cells
In Vitro Effect of Carboplatin, Cytarabine, Paclitaxel, Vincristine, and Low-Power Laser Irradiation on Murine Mesenchymal Stem Cells
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DOI：
10.1002/lsm.20791
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发表时间：
2009-08-01
影响因子：
2.4
通讯作者：
Uher, Ferenc
中科院分区：
文献类型：
--
作者：
Horvat-Karajz, Karoly;Balogh, Zsuzsanna;Uher, Ferenc
背景与目的：间充质干细胞（MSCs）在再生医学中具有广阔的应用前景。细胞抑制因子会降低，但低功率激光照射（LPLI）可以促进MSCs的生长。LPLI、MSCs和细胞抑制剂的相互作用尚不清楚。本研究探讨了四种细胞抑制剂（卡铂、阿糖胞苷、紫杉醇、长春新碱）、LPLI以及一种细胞抑制剂药物与LPLI联合使用对小鼠间充质干细胞（mMSCs）的影响。研究设计/材料和方法：将MMSCs暴露于LPLI (660 nm二极管激光器，输出功率为60 mW，功率密度范围：76-1.56 mW/cm(2)；能量密度范围：1.9-11.7 J/cm(2))和/或细胞抑制剂（卡铂：2、10、50；阿糖胞苷：0.4、10、50；紫杉醇：0.4、2、10；长春新碱：0.02、0.1、0.5 μ g/ml）。孵育24、48、72小时后测定细胞增殖。结果：1.9 J/cm(2)剂量的LPLI可使48h后的增殖率提高41%。然而，11.7 J/cm(2) LPLI在72小时后仍可检测到42%的抑制作用和细胞停滞。LPLI在24小时内单次或分次剂量均可产生相同的刺激（3.8 vs.两次1.9 J/cm(2)）。50 μ g/ml卡铂的细胞毒性被消除，0.1 μ g/ml长春新碱的抑制能力在治疗后3天被1.9 J/cm(2) LPLI减弱（衰减bbb10 %）。11.7 J/cm(2) LPLI使50 μ g/ml阿糖胞苷（从48%提高到73%）和10 μ g/ml紫杉醇（从37%提高到78%）的细胞毒性增强。无效的0.4 μ g/ml阿糖胞苷或紫杉醇与具有抑制作用的11.7 J/cm(2) LPLI联合使用比单独使用11.7 J/cm(2) LPLI更强（69%和69% vs. 42%）。结论：低能量密度的LPLI增加了mmsc的增殖，高能量密度的LPLI减少了mmsc的增殖。此外，LPLI可以预防或减弱某些药物的细胞毒性，并增强其他药物的细胞毒性。结果取决于所施加的能量密度、细胞抑制剂的类型和浓度。激光外科杂志，2009。(C) 2009 Wiley-Liss, Inc。
Background and Objectives: Mesenchymal stem cells (MSCs) are promising for use in regenerative medicine. Cytostatics can decrease, but low-power laser irradiation (LPLI) can increase the growth of MSCs. The interaction of LPLI, MSCs and cytostatics is not known. This study investigated the effect of four cytostatics (carboplatin, cytarabine, paclitaxel, vincristine), LPLI, and combination of a cytostatic drug and LPLI on murine MSCs (mMSCs).Study Design/Materials and Methods: MMSCs were exposed to LPLI (660 nm diode laser; 60 mW output power; range of power density: 76-1.56 mW/cm(2); range of energy density: 1.9-11.7 J/cm(2)) and/or a cytostatic drug (carboplatin: 2,10,50; cytarabine: 0.4,10,50; paclitaxel: 0.4, 2, 10; vincristine: 0.02, 0.1, 0.5 mu g/ml, respectively). Cell proliferation was measured after 24, 48, or 72 hours incubation.Results: LPLI at 1.9 J/cm(2) dose increased the proliferation rate with 41% after 48hours. However, 11.7 J/cm(2) LPLI caused 42% inhibition and cytostasis was still detectable after 72hours. LPLI caused equivalent stimulation in single or in divided doses (3.8 vs. double 1.9 J/cm(2) in a 24-hour period). The cytotoxicity of 50 mu g/ml carboplatin was eliminated, the inhibitory power of 0.1 mu g/ml vincristine was attenuated by 1.9 J/cm(2) LPLI even 3 days post-treatment (attenuation > 10%). The 11.7 J/cm(2) LPLI enhanced the cytotoxicity of 50 mu g/ml cytarabine (from 48% to 73%) and 10 mu g/ml paclitaxel (from 37% to 78%). Combination of the ineffective 0.4 mu g/ml cytarabine or paclitaxel with the inhibitory 11.7 J/cm(2) LPLI exhibited stronger inhibition than the 11.7 J/cm(2) LPLI alone (69% and 69% vs. 42%).Conclusions: Low energy density of LPLI increases and high energy density of LPLI decreases the proliferation of mMSCs. Furthermore, LPLI can prevent or attenuate some drug's cytotoxicity and amplify others'. The result depends on the applied energy density, on the type and concentration of the cytostatics. Lasers Surg. Med. 41:463-469, 2009. (C) 2009 Wiley-Liss, Inc.