The Anterior Eye Chamber as a Visible Medium for In Vivo Tumorigenicity Tests.
The Anterior Eye Chamber as a Visible Medium for In Vivo Tumorigenicity Tests.
复制标题
DOI：
10.1093/stcltm/szac036
复制
发表时间：
2022-08-23
影响因子：
6
通讯作者：
Shimmura, Shigeto
中科院分区：
文献类型：
--
作者：
Inagaki, Emi;Arai, Eri;Hatou, Shin;Sayano, Tomoko;Taniguchi, Hiroko;Negishi, Kazuno;Kanai, Yae;Sato, Yasunori;Okano, Hideyuki;Tsubota, Kazuo;Shimmura, Shigeto
在过去的几年中，基于多能干细胞（PSC）的细胞疗法稳步增长，评估肿瘤形成的风险是临床研究的重中之重。目前的体内肿瘤发生研究需要几个月的时间，并且很大程度上取决于移植的位置。在这项研究中，我们报告了由于几个原因，前房比皮下空间更适合体内肿瘤发生研究。首先，由于角膜的透明性，可以很容易地将细胞移植到前房并进行实时监测，而不会牺牲动物。其次，肿瘤的形成速度比传统的皮下方法快。皮下中位肿瘤形成时间为18.50周（95% CI 10.20-26.29），前房中位肿瘤形成时间为4.0周（95% CI 3.34- 0.67） （P = 0.0089）。当hipsc中加入成纤维细胞时，log10TPD50为3.26，而hipsc中不加入成纤维细胞时，log10TPD50为4.99。成纤维细胞的log10TPD50值差异超过40倍。此外，HeLa细胞的log10TPD50为1.45，浓度大于0.1%时，100%的动物形成肿瘤，表明前房肿瘤发生实验也可以应用于癌细胞系。因此，我们的方法有潜力成为肿瘤发生研究和癌症研究的所有领域的有力工具。
Pluripotent stem cell (PSC)-based cell therapies have increased steadily over the past few years, and assessing the risk of tumor formation is a high priority for clinical studies. Current in vivo tumorigenesis studies require several months and depend strongly on the site of grafting. In this study, we report that the anterior eye chamber is preferable to the subcutaneous space for in vivo tumorigenesis studies for several reasons. First, cells can easily be transplanted into the anterior chamber and monitored in real-time without sacrificing the animals due to the transparency of the cornea. Second, tumor formation is faster than with the conventional subcutaneous method. The median tumor formation time in the subcutaneous area was 18.50 weeks (95% CI 10.20-26.29), vs. 4.0 weeks (95% CI 3.34-.67) in the anterior chamber (P = .0089). When hiPSCs were spiked with fibroblasts, the log10TPD50 was 3.26, compared with 4.99 when hiPSCs were transplanted without fibroblasts. There was more than a 40-fold difference in the log10TPD50 values with fibroblasts. Furthermore, the log10TPD50 for HeLa cells was 1.45 and 100% of animals formed tumors at a concentration greater than 0.1%, indicating that the anterior chamber tumorigenesis assays can be applied for cancer cell lines as well. Thus, our method has the potential to become a powerful tool in all areas of tumorigenesis studies and cancer research.
登录
查看更多内容
影响因子：
6
作者：
Inagaki E;Hatou S;Higa K;Yoshida S;Shibata S;Okano H;Tsubota K;Shimmura S
通讯作者：
Shimmura S
影响因子：
4.6
作者：
Kusakawa S;Yasuda S;Kuroda T;Kawamata S;Sato Y
通讯作者：
Sato Y
影响因子：
2.2
作者：
Bonicel, P;Michelot, J;Madelmont, JC
通讯作者：
Madelmont, JC
影响因子：
4.1
作者：
Keino H;Horie S;Sugita S
通讯作者：
Sugita S
影响因子：
4.4
作者：
Notting, IC;Buijs, JT;van der Pluijm, G
通讯作者：
van der Pluijm, G