Paclitaxel Priming of TRAIL Expressing Mesenchymal Stromal Cells (MSCs-TRAIL) Increases Antitumor Efficacy of Their Secretome
Paclitaxel Priming of TRAIL Expressing Mesenchymal Stromal Cells (MSCs-TRAIL) Increases Antitumor Efficacy of Their Secretome
复制标题
DOI：
10.2174/1568009620666201116112153
复制
发表时间：
2021-01-01
影响因子：
3
通讯作者：
Pessina, Augusto
中科院分区：
文献类型：
--
作者：
Cocce, Valentina;Bonomi, Arianna;Pessina, Augusto
背景：用肿瘤坏死因子相关凋亡诱导配体蛋白（MSCs-TRAIL）改造的脂肪组织来源的间充质干细胞具有显着的抗癌活性。未经任何基因修饰的间充质干细胞暴露于高剂量的化疗药物后能够吸收药物并释放一定量的药物，从而影响肿瘤的增殖。本研究的目的是验证 MSCs-TRAIL 摄取和释放紫杉醇 (PTX) 的能力，从而提高抗肿瘤功效。方法：通过 MTT 法检测 MSCs 和 MSCs-TRAIL 对紫杉醇 (PTX) 的敏感性，并根据标准化程序加载 PTX。通过 HPLC 分析分泌蛋白组中 PTX 的存在，微阵列测定可溶性 TRAIL (s-TRAIL) 并测试体外抗癌活性。结果：MSCs-TRAIL 对 PTX 具有抗性，能够掺入并释放药物。装载 PTX 的 MSCs-TRAIL 的 s-TRAIL 分泌没有受到抑制，并且在人胰腺癌 (CFPAC-1) 和胶质母细胞瘤 (U87-MG) 的体外测试中，PTX 递送与 s-TRAIL 分泌一起导致细胞分泌组的抗肿瘤功效增加。结论：我们的结果首次证明了基于基因操作和药物递送的两种新 MSC 治疗方法可能合并的可能性。如果在体内得到证实，这可能会增强 MSCs-TRAIL 的功效，并大大有助于降低 PTX 全身治疗引起的毒性。
Background: Adipose tissue-derived MSCs engineered with the tumor necrosis factor-related apoptosis-inducing ligand protein (MSCs-TRAIL) have significant anticancer activity. MSCs, without any genetic modifications, exposed to high doses of chemotherapeutic agents are able to uptake the drug and release it in an amount affecting tumor proliferation. The purpose of this study was to verify the ability of MSCs-TRAIL to uptake and release paclitaxel (PTX) by providing an increased antitumor efficacy.Methods: MSCs and MSCs-TRAIL were tested for their sensitivity to Paclitaxel (PTX) by MTT assay, and the cells were loaded with PTX according to a standardized procedure. The secretome was analysed by HPLC for the presence of PTX, microarray assay for soluble TRAIL (s-TRAIL) and tested for in vitro anticancer activity.Results: MSCs-TRAIL were resistant to PTX and able to incorporate and then release the drug. The secretion of s-TRAIL by PTX loaded MSCs-TRAIL was not inhibited, and the PTX delivery together with s-TRAIL secretion resulted in increased antitumor efficacy of cell secretome as tested in vitro on human pancreatic carcinoma (CFPAC-1) and glioblastoma (U87-MG).Conclusion: Our result is the first demonstration of the possible merging of two new MSCs therapy approaches based on genetic manipulation and drug delivery. If confirmed in vivo, this could potentiate the efficacy of MSCs-TRAIL and strongly contribute to reducing the toxicity due to the systemic treatment of PTX.