PMID- 26512920
OWN - NLM
STAT- MEDLINE
DCOM- 20160922
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 38
DP  - 2015 Dec 1
TI  - A biotherapy based on PSCs-in-3D spheroid-ameliorated biologics depletes in vivo 
      cancer-sustaining stem cells.
PG  - 40762-74
LID - 10.18632/oncotarget.5691 [doi]
AB  - 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-alpha1 ~ beta4 
      in thymic cortex-medulla borderline for rapid MHC-unrestricted renewal of 
      gammadeltaT-dominated immunocompetence. The post-renewal gammadeltaT-subsets could accurately 
      bind and drive CSCs into apoptosis. Finally, with central/peripheral integral 
      microenvironment renewal and TERT/Wnt/beta-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.
FAU - Zhang, Wenhui
AU  - Zhang W
AD  - National Key Laboratory of Biotherapy/Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's 
      Republic of China.
FAU - Yang, Huanhuan
AU  - Yang H
AD  - National Key Laboratory of Biotherapy/Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's 
      Republic of China.
FAU - Zhang, Yanna
AU  - Zhang Y
AD  - National Key Laboratory of Biotherapy/Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's 
      Republic of China.
FAU - Lu, Yanan
AU  - Lu Y
AD  - National Key Laboratory of Biotherapy/Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's 
      Republic of China.
FAU - Zhou, Tianlin
AU  - Zhou T
AD  - National Key Laboratory of Biotherapy/Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's 
      Republic of China.
FAU - Li, Meng
AU  - Li M
AD  - National Key Laboratory of Biotherapy/Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's 
      Republic of China.
FAU - Wen, Yanjun
AU  - Wen Y
AD  - Department of Gynecology & Obstetrics, West China Hospital/Second Hospital, 
      Sichuan University, Chengdu, Sichuan, People's Republic of China.
FAU - Lin, Xiaojuan
AU  - Lin X
AD  - Department of Gynecology & Obstetrics, West China Hospital/Second Hospital, 
      Sichuan University, Chengdu, Sichuan, People's Republic of China.
FAU - Xiang, Rong
AU  - Xiang R
AD  - Department of Immunology, Nankai University School of Medicine, Tianjin, People's 
      Republic of China.
FAU - Chen, Xiancheng
AU  - Chen X
AD  - National Key Laboratory of Biotherapy/Collaborative Innovation Center for 
      Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's 
      Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Biological Products)
RN  - 0 (RNA, Messenger)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Biological Products/*administration & dosage
MH  - *Biological Therapy
MH  - Blotting, Western
MH  - Cell Proliferation
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Neoplasms/metabolism/pathology/*therapy
MH  - Neoplastic Stem Cells/metabolism/*pathology
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Spheroids, Cellular/metabolism/*pathology
MH  - Thymus Gland/*cytology/immunology/metabolism
MH  - Tumor Cells, Cultured
MH  - Wnt Signaling Pathway
MH  - Xenograft Model Antitumor Assays
MH  - beta Catenin/genetics/metabolism
PMC - PMC4747367
OTO - NOTNLM
OT  - 3D-spheroid
OT  - immune renewal
OT  - molecule microenvironment
OT  - stem cells
COIS- CONFLICTS OF INTEREST The authors disclose no potential conflicts of interest.
EDAT- 2015/10/30 06:00
MHDA- 2016/09/23 06:00
PMCR- 2015/12/01
CRDT- 2015/10/30 06:00
PHST- 2015/04/04 00:00 [received]
PHST- 2015/09/14 00:00 [accepted]
PHST- 2015/10/30 06:00 [entrez]
PHST- 2015/10/30 06:00 [pubmed]
PHST- 2016/09/23 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - 5691 [pii]
AID - 10.18632/oncotarget.5691 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Dec 1;6(38):40762-74. doi: 10.18632/oncotarget.5691.