title: Tumourigenicity and Immunogenicity of Induced Neural Stem Cell Grafts Versus Induced Pluripotent Stem Cell Grafts in Syngeneic Mouse Brain.
abstract: Along with the development of stem cell-based therapies for central nervous system (CNS) disease, the safety of stem cell grafts in the CNS, such as induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs), should be of primary concern. To provide scientific basis for evaluating the safety of these stem cells, we determined their tumourigenicity and immunogenicity in syngeneic mouse brain. Both iPSCs and embryonic stem cells (ESCs) were able to form tumours in the mouse brain, leading to tissue destruction along with immune cell infiltration. In contrast, no evidence of tumour formation, brain injury or immune rejection was observed with iNSCs, neural stem cells (NSCs) or mesenchymal stem cells (MSCs). With the help of gene ontology (GO) enrichment analysis, we detected significantly elevated levels of chemokines in the brain tissue and serum of mice that developed tumours after ESC or iPSC transplantation. Moreover, we also investigated the interactions between chemokines and NF-κB signalling and found that NF-κB activation was positively correlated with the constantly rising levels of chemokines, and vice versa. In short, iNSC grafts, which lacked any resulting tumourigenicity or immunogenicity, are safer than iPSC grafts.
authors.affiliation: Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.|Affiliated Bayi Brain hospital, General Hospital of PLA Army, Beijing 100700, China.
authors.forename: Mou
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.|Affiliated Bayi Brain hospital, General Hospital of PLA Army, Beijing 100700, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Neurology, Fu Xing Hospital, Capital Medical University, Beijing 100038, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.|Affiliated Bayi Brain hospital, General Hospital of PLA Army, Beijing 100700, China.
authors.forename: Hongtian
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.|Affiliated Bayi Brain hospital, General Hospital of PLA Army, Beijing 100700, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.|Affiliated Bayi Brain hospital, General Hospital of PLA Army, Beijing 100700, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.|Affiliated Bayi Brain hospital, General Hospital of PLA Army, Beijing 100700, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.|Affiliated Bayi Brain hospital, General Hospital of PLA Army, Beijing 100700, China.
authors.forename: Minhui
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.|Affiliated Bayi Brain hospital, General Hospital of PLA Army, Beijing 100700, China.
authors.forename: Ruxiang
authors.initials: R
authors.lastname: Xu
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D063646:Carcinogenesis / Q000276:immunology* / Q000473:pathology*; D018925:Chemokines / Q000097:blood / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D058953:Neural Stem Cells / Q000276:immunology* / Q000473:pathology* / Q000637:transplantation; D033581:Stem Cell Transplantation; D014185:Transplantation, Isogeneic
chemical_list: D018925:Chemokines; D016328:NF-kappa B