Zhang Wenhui, Yang Huanhuan, Zhang Yanna, Lu Yanan, Zhou Tianlin, Li Meng, Wen Yanjun, Lin Xiaojuan, Xiang Rong, Chen Xiancheng
National Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Department of Gynecology & Obstetrics, West China Hospital/Second Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Oncotarget. 2015 Dec 1;6(38):40762-74. doi: 10.18632/oncotarget.5691.
CSCs are able to survive routine anticancer procedures and peripheral-immune attack. Here we develop and detail a framework of CSC elimination governed by 3D-biologics. Pluripotent cells-engineered 3D-biologics (PMSB) and control non-3D-biologics were prepared from placenta-based somatic stem cells (PSCs) and inoculated respectively into senile hosts bearing progressive mammary, lung, colon carcinomas and melanoma. We demonstrate that PMSB evokes in vivo central-immune microenvironment with subsequent re-expression of thymosin-α1 ~ β4 in thymic cortex-medulla borderline for rapid MHC-unrestricted renewal of γδT-dominated immunocompetence. The post-renewal γδT-subsets could accurately bind and drive CSCs into apoptosis. Finally, with central/peripheral integral microenvironment renewal and TERT/Wnt/β-catenin pathway blockade, the CSC-subsets are fully depleted, leading to substantial cure of diverse tumors by PMSB inoculation (P < 0.01), yet not by non-3D-biologics. Thus, our study may contribute to open up a new avenue for tumor remission via pluripotent cells-engineered 3D-biologics addressing quick renewal of central-thymus and peripheral immune-microenvironment.
癌症干细胞能够在常规抗癌程序和外周免疫攻击中存活。在此，我们开发并详细阐述了一种由三维生物制剂控制的癌症干细胞消除框架。从胎盘来源的体细胞干细胞（PSC）制备多能细胞工程化三维生物制剂（PMSB）和对照非三维生物制剂，并分别接种到患有进行性乳腺癌、肺癌、结肠癌和黑色素瘤的老年宿主中。我们证明，PMSB在体内引发中枢免疫微环境，随后胸腺皮质-髓质交界处的胸腺素-α1至β4重新表达，以快速进行不受主要组织相容性复合体（MHC）限制的γδT细胞主导的免疫能力更新。更新后的γδT细胞亚群能够准确结合并促使癌症干细胞凋亡。最后，通过中枢/外周整体微环境更新以及端粒酶逆转录酶（TERT）/Wnt/β-连环蛋白信号通路阻断，癌症干细胞亚群被完全清除，通过接种PMSB可使多种肿瘤得到实质性治愈（P < 0.01），而非三维生物制剂则无此效果。因此，我们的研究可能有助于开辟一条通过多能细胞工程化三维生物制剂实现肿瘤缓解的新途径，该制剂可解决中枢胸腺和外周免疫微环境的快速更新问题。
