PMID- 25071759
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140729
LR  - 20211021
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 5
DP  - 2014
TI  - Embryonic Stem Cells Promoting Macrophage Survival and Function are Crucial for 
      Teratoma Development.
PG  - 275
LID - 10.3389/fimmu.2014.00275 [doi]
LID - 275
AB  - Stem cell therapies have had tremendous potential application for many diseases 
      in recent years. However, the tumorigenic properties of stem cells restrict their 
      potential clinical application; therefore, strategies for reducing the 
      tumorigenic potential of stem cells must be established prior to transplantation. 
      We have demonstrated that syngeneic transplantation of embryonic stem cells 
      (ESCs) provokes an inflammatory response that involves the rapid recruitment of 
      bone marrow-derived macrophages (BMDMs). ESCs are able to prevent mature 
      macrophages from macrophage colony-stimulating factor (M-CSF) withdrawal-induced 
      apoptosis, and thus prolong macrophage lifespan significantly by blocking various 
      apoptotic pathways in an M-CSF-independent manner. ESCs express and secrete 
      IL-34, which may be responsible for ESC-promoted macrophage survival. This 
      anti-apoptotic effect of ESCs involves activation of extracellular 
      signal-regulated kinase (ERK)1/2 and PI3K/Akt pathways and thus, inhibition of 
      ERK1/2 and PI3K/AKT activation decreases ESC-induced macrophage survival. 
      Functionally, ESC-treated macrophages also showed a higher level of phagocytic 
      activity. ESCs further serve to polarize BMDMs into M2-like macrophages that 
      exhibit most tumor-associated macrophage phenotypic and functional features. 
      ESC-educated macrophages produce high levels of arginase-1, Tie-2, and TNF-alpha, 
      which participate in angiogenesis and contribute to teratoma progression. Our 
      study suggests that induction of M2-like macrophage activation is an important 
      mechanism for teratoma development. Strategies targeting macrophages to inhibit 
      teratoma development would increase the safety of ESC-based therapies, inasmuch 
      as the depletion of macrophages completely inhibits ESC-induced angiogenesis and 
      teratoma development.
FAU - Chen, Tianxiang
AU  - Chen T
AD  - W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University 
      of New Jersey , New Jersey, NJ , USA ; Department of Thoracic Surgery, First 
      Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
FAU - Wang, Xi
AU  - Wang X
AD  - W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University 
      of New Jersey , New Jersey, NJ , USA ; Institute of Neurosciences, The Fourth 
      Military Medical University , Xian , China.
FAU - Guo, Lei
AU  - Guo L
AD  - Department of Biomedical Sciences, Florida State University College of Medicine , 
      Tallahassee, FL , USA ; Department of Orthopedic Surgery, The Second Hospital of 
      Xian Jiaotong University , Xian , China.
FAU - Wu, Mingmei
AU  - Wu M
AD  - W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University 
      of New Jersey , New Jersey, NJ , USA.
FAU - Duan, Zhaoxia
AU  - Duan Z
AD  - W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University 
      of New Jersey , New Jersey, NJ , USA.
FAU - Lv, Jing
AU  - Lv J
AD  - Department of Biomedical Sciences, Florida State University College of Medicine , 
      Tallahassee, FL , USA.
FAU - Tai, Wenjiao
AU  - Tai W
AD  - Department of Biomedical Sciences, Florida State University College of Medicine , 
      Tallahassee, FL , USA.
FAU - Renganathan, Hemamalini
AU  - Renganathan H
AD  - W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University 
      of New Jersey , New Jersey, NJ , USA.
FAU - Didier, Ruth
AU  - Didier R
AD  - Department of Biomedical Sciences, Florida State University College of Medicine , 
      Tallahassee, FL , USA.
FAU - Li, Jinhua
AU  - Li J
AD  - Department of Anatomy and Developmental Biology, Monash University , Clayton, VIC 
      , Australia.
FAU - Sun, Dongming
AU  - Sun D
AD  - W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University 
      of New Jersey , New Jersey, NJ , USA.
FAU - Chen, Xiaoming
AU  - Chen X
AD  - Institute of Translational Medicine, First Affiliated Hospital, Wenzhou Medical 
      University , Wenzhou , China.
FAU - He, Xijing
AU  - He X
AD  - Department of Orthopedic Surgery, The Second Hospital of Xian Jiaotong University 
      , Xian , China.
FAU - Fan, Jianqing
AU  - Fan J
AD  - Statistics Laboratory, Princeton University , Princeton, NJ , USA.
FAU - Young, Wise
AU  - Young W
AD  - W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University 
      of New Jersey , New Jersey, NJ , USA.
FAU - Ren, Yi
AU  - Ren Y
AD  - Department of Biomedical Sciences, Florida State University College of Medicine , 
      Tallahassee, FL , USA.
LA  - eng
GR  - R01 GM100474/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20140704
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC4082241
OTO - NOTNLM
OT  - angiogenesis
OT  - apoptosis
OT  - embryonic stem cells
OT  - macrophages
OT  - teratoma
EDAT- 2014/07/30 06:00
MHDA- 2014/07/30 06:01
PMCR- 2014/01/01
CRDT- 2014/07/30 06:00
PHST- 2014/04/02 00:00 [received]
PHST- 2014/05/27 00:00 [accepted]
PHST- 2014/07/30 06:00 [entrez]
PHST- 2014/07/30 06:00 [pubmed]
PHST- 2014/07/30 06:01 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2014.00275 [doi]
PST - epublish
SO  - Front Immunol. 2014 Jul 4;5:275. doi: 10.3389/fimmu.2014.00275. eCollection 2014.