title: A biotherapy based on PSCs-in-3D spheroid-ameliorated biologics depletes in vivo cancer-sustaining stem cells.
abstract: 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.
authors.affiliation: National Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Yang
authors.affiliation: National Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: National Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Tianlin
authors.initials: T
authors.lastname: Zhou
authors.affiliation: National Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Gynecology & Obstetrics, West China Hospital/Second Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Department of Gynecology & Obstetrics, West China Hospital/Second Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Immunology, Nankai University School of Medicine, Tianjin, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: National Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Xiancheng
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D001688:Biological Products / Q000008:administration & dosage*; D001691:Biological Therapy; D015153:Blotting, Western; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D060449:Wnt Signaling Pathway; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D001688:Biological Products; D012333:RNA, Messenger; D051176:beta Catenin
keywords: 3D-spheroid; immune renewal; molecule microenvironment; stem cells