A biotherapy based on PSCs-in-3D spheroid-ameliorated biologics depletes in vivo cancer-sustaining stem cells
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Wenhui Zhang1,*, Huanhuan Yang1,*, Yanna Zhang1,*, Yanan Lu1,*, Tianlin Zhou1, Meng Li1, Yanjun Wen2, Xiaojuan Lin2, Rong Xiang3, Xiancheng Chen1
1National Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
2Department of Gynecology & Obstetrics, West China Hospital/Second Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
3Department of Immunology, Nankai University School of Medicine, Tianjin, People's Republic of China
*These authors have contributed equally to this work
Keywords: stem cells, 3D-spheroid, molecule microenvironment, immune renewal
Received: April 04, 2015 Accepted: September 14, 2015 Published: October 19, 2015
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.
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