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Embryonic Stem Cells Promoting Macrophage Survival and Function are Crucial for Teratoma Development.

Title: Embryonic Stem Cells Promoting Macrophage Survival and Function are Crucial for Teratoma Development.
Name(s): Chen, Tianxiang, author
Wang, Xi, author
Guo, Lei, author
Wu, Mingmei, author
Duan, Zhaoxia, author
Lv, Jing, author
Tai, Wenjiao, author
Renganathan, Hemamalini, author
Didier, Ruth, author
Li, Jinhua, author
Sun, Dongming, author
Chen, Xiaoming, author
He, Xijing, author
Fan, Jianqing, author
Young, Wise, author
Ren, Yi, author
Type of Resource: text
Genre: Journal Article
Date Issued: 2014-07-04
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: 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-α, 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.
Identifier: FSU_pmch_25071759 (IID), 10.3389/fimmu.2014.00275 (DOI), PMC4082241 (PMCID), 25071759 (RID), 25071759 (EID)
Keywords: Angiogenesis, Apoptosis, Embryonic stem cells, Macrophages, Teratoma
Grant Number: R01 GM100474
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at
Persistent Link to This Record:
Owner Institution: FSU
Is Part Of: Frontiers in immunology.
Issue: vol. 5

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Chen, T., Wang, X., Guo, L., Wu, M., Duan, Z., Lv, J., … Ren, Y. (2014). Embryonic Stem Cells Promoting Macrophage Survival and Function are Crucial for Teratoma Development. Frontiers In Immunology. Retrieved from