Kupffer cells-dependent inflammation in the injured liver increases recruitment of mesenchymal stem cells in aging mice

// Xue Yang 1,* , Lei Liang 1,2,* , Chen Zong 1 , Fobao Lai 1 , Pengxi Zhu 3 , Yu Liu 4 , Jinghua Jiang 1 , Yang Yang 1 , Lu Gao 1 , Fei Ye 1 , Qiudong Zhao 1 , Rong Li 1 , Zhipeng Han 1 and Lixin Wei 1 1 Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China 2 Medical College of Soochow University, Suzhou, China 3 Department of Pharmacy, Chang Hai Hospital, the Second Military Medical University, Shanghai, China 4 College of Art and Science, University of San Francisco, San Francisco, CA, USA * These authors have contributed equally to this work Correspondence to: Lixin Wei, email: // Zhipeng Han, email: // Keywords : aging, mesenchymal stem cells, recruitment, liver injury, Gerotarget Received : August 23, 2015 Accepted : November 22, 2015 Published : December 23, 2015 Abstract Mesenchymal stem cells (MSCs) repair tissue injury and may be used to treat immune associated diseases. In carbon tetrachloride (CCl4)-induced liver injury murine model, we administered MSCs. When MSCs were transmitted to young and old mice with liver injury, more MSCs were recruited in old mice. In old mice, inflammation, characterized by TNF-α and IL-6, was increased due to hyper-activation and hyper-function of Kupffer cells. Blocking Kupffer cells decreased MSCs migration in old mice. In vitro , Kupffer cells isolated from old mice secreted more inflammatory cytokines and chemokines. Thus, hyper-activation of Kupffer cells in old mice increased recruitment of MSCs after their therapeutic administration.