Immortalized Mesenchymal Stem Cells: A Safe Cell Source for Cellular or Cell Membrane-Based Treatment of Glioma.
Immortalized Mesenchymal Stem Cells: A Safe Cell Source for Cellular or Cell Membrane-Based Treatment of Glioma.
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DOI：
10.1155/2022/6430565
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发表时间：
2022
影响因子：
4.3
通讯作者：
Wang, Jihui
中科院分区：
文献类型：
--
作者：
Zhang, Yuxuan;Liu, Jie;Mo, Yunzhao;Chen, Zetao;Chen, Taoliang;Li, Yan;Zheng, Yaofeng;Deng, Shaokang;Xu, Xiangdong;Chen, Huajian;He, Haoqi;Chen, Jiansheng;Jin, Tao;Sun, Xinlin;Ke, Yiquan;Wang, Jihui
间充质干细胞（MSC）由于其固有的肿瘤向性、抗肿瘤和免疫调节特性而成为公认的治疗工具。骨髓间充质干细胞在体外有限的传代和自我分化能力阻碍了其临床前研究。在这项研究中，我们专注于永生化间充质干细胞（im-MSCs）的安全性，并首次研究了im-MSCs作为治疗胶质瘤候选细胞的可行性。通过慢病毒转染基因构建im-MSCs。使用CCK-8或EdU测定法测量im-MSCs的增殖能力以及MSCs和与胶质瘤细胞（U87）共培养的MSCs的增殖表型。长期培养后，对im-MSCs进行核型分析。采用软琼脂克隆形成实验评价工程化MSCs的致瘤性。接下来，将工程化细胞注射到雌性BALB/c裸鼠的脑中。最后，用DiO或DiR标记im-MSC的细胞膜，以使用IVIS系统检测它们被胶质瘤细胞摄取和靶向原位胶质瘤的能力。工程化细胞保留了MSC的免疫表型; im-MSCs保持了体外分化为间充质谱系的能力; im-MSCs表现出比未工程化的MSCs更强的增殖能力，但在软琼脂中没有集落形成，脑中没有致瘤性，染色体正常。骨髓间充质干细胞或im-MSCs与U87细胞共培养后，体外增殖能力增强，但未显示恶性特征。永生化细胞继续表达归巢分子。im-MSCs的细胞膜被胶质瘤细胞摄取并在体内原位靶向胶质瘤，表明im-MSCs及其质膜可作为天然药物载体靶向胶质瘤，为基于全细胞或细胞膜载体的胶质瘤治疗提供安全、充足、质量可控和连续的来源。
Mesenchymal stem cells (MSCs) have emerged as putative therapeutic tools due to their intrinsic tumor tropism, and anti-tumor and immunoregulatory properties. The limited passage and self-differentiation abilities of MSCs in vitro hinder preclinical studies on them. In this study, we focused on the safety of immortalized mesenchymal stem cells (im-MSCs) and, for the first time, studied the feasibility of im-MSCs as candidates for the treatment of glioma. The im-MSCs were constructed by lentiviral transfection of genes. The proliferative capacity of im-MSCs and the proliferative phenotype of MSCs and MSCs co-cultured with glioma cells (U87) were measured using CCK-8 or EdU assays. After long-term culture, karyotyping of im-MSCs was conducted. The tumorigenicity of engineered MSCs was evaluated using soft agar cloning assays. Next, the engineered cells were injected into the brain of female BALB/c nude mice. Finally, the cell membranes of im-MSCs were labeled with DiO or DiR to detect their ability to be taken up by glioma cells and target in situ gliomas using the IVIS system. Engineered cells retained the immunophenotype of MSC; im-MSCs maintained the ability to differentiate into mesenchymal lineages in vitro; and im-MSCs showed stronger proliferative capacity than unengineered MSCs but without colony formation in soft agar, no tumorigenicity in the brain, and normal chromosomes. MSCs or im-MSCs co-cultured with U87 cells showed enhanced proliferation ability, but did not show malignant characteristics in vitro. Immortalized cells continued to express homing molecules. The cell membranes of im-MSCs were taken up by glioma cells and targeted in situ gliomas in vivo, suggesting that im-MSCs and their plasma membranes can be used as natural drug carriers for targeting gliomas, and providing a safe, adequate, quality-controlled, and continuous source for the treatment of gliomas based on whole-cell or cell membrane carriers.
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用于增强抗肿瘤治疗的自递送膜系统
影响因子：
14
作者：
Qiu, Wen-Xiu;Zhang, Ming-Kang;Zhang, Xian-Zheng
通讯作者：
Zhang, Xian-Zheng
影响因子：
14.8
作者：
Suski, Jan M.;Lebiedzinska, Magdalena;Wieckowski, Mariusz R.
通讯作者：
Wieckowski, Mariusz R.
永生化间充质干细胞：神经元分化和神经再生相关研究中原代间充质干细胞的替代品
影响因子：
11
作者：
Gong M;Bi Y;Jiang W;Zhang Y;Chen L;Hou N;Liu Y;Wei X;Chen J;Li T
通讯作者：
Li T
DOI：
10.1038/mtna.2013.60
发表时间：
2013-10-01
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
--
影响因子：
9.7
作者：
Katakowski, Mark;Buller, Ben;Zheng, Xuguang;Lu, Yong;Rogers, Thomas;Osobamiro, Oyinkansola;Shu, Wayne;Jiang, Feng;Chopp, Michael
通讯作者：
Chopp, Michael