MIF produced by bone marrow-derived macrophages contributes to teratoma progression after embryonic stem cell transplantation

Xi Wang, Tianxiang Chen, Lin Leng, Jianqing Fan, Kai Cao, Zhaoxia Duan, Xijing Zhang, Changshun Shao, Mingmei Wu, Iman Tadmori, Tianyi Li, Li Liang, Dongming Sun, Shusen Zheng, Andreas Meinhardt, Wise Young, Richard Bucala, Yi Ren

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Although stem cell therapy holds promise as a potential treatment in a number of diseases, the tumorigenicity of embryonic stem cells (ESC) and induced pluripotent stem cells remains a major obstacle. In vitro predifferentiation of ESCs can help prevent the risk of teratoma formation, yet proliferating neural progenitors can generate tumors, especially in the presence of immunosuppressive therapy. In this study, we investigated the effects of the microenvironment on stem cell growth and teratoma development using undifferentiated ESCs. Syngeneic ESC transplantation triggered an inflammatory response that involved the recruitment of bone marrow (BM)-derived macrophages. These macrophages differentiated into an M2 or angiogenic phenotype that expressed multiple angiogenic growth factors and proteinases, such as macrophage migration inhibitory factor (MIF), VEGF, and matrix metalloproteinase 9, creating a microenvironment that supported the initiation of teratoma development. Genetic deletion of MIF from the host but not from ESCs specifically reduced angiogenesis and teratoma growth, and MIF inhibition effectively reduced teratoma development after ESC transplantation. Together, our findings show that syngeneic ESC transplantation provokes an inflammatory response that involves the rapid recruitment and activation of BM-derived macrophages, which may be a crucial driving force in the initiation and progression of teratomas.

Original languageEnglish (US)
Pages (from-to)2867-2878
Number of pages12
JournalCancer Research
Volume72
Issue number11
DOIs
StatePublished - Jun 1 2012

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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