title: Sensitive Tumorigenic Potential Evaluation of Adult Human Multipotent Neural Cells Immortalized by hTERT Gene Transduction.
abstract: Stem cells and therapeutic genes are emerging as a new therapeutic approach to treat various neurodegenerative diseases with few effective treatment options. However, potential formation of tumors by stem cells has hampered their clinical application. Moreover, adequate preclinical platforms to precisely test tumorigenic potential of stem cells are controversial. In this study, we compared the sensitivity of various animal models for in vivo stem cell tumorigenicity testing to identify the most sensitive platform. Then, tumorigenic potential of adult human multipotent neural cells (ahMNCs) immortalized by the human telomerase reverse transcriptase (hTERT) gene was examined as a stem cell model with therapeutic genes. When human glioblastoma (GBM) cells were injected into adult (4-6-week-old) Balb/c-nu, adult NOD/SCID, adult NOG, or neonate (1-2-week-old) NOG mice, the neonate NOG mice showed significantly faster tumorigenesis than that of the other groups regardless of intracranial or subcutaneous injection route. Two kinds of ahMNCs (682TL and 779TL) were primary cultured from surgical samples of patients with temporal lobe epilepsy. Although the ahMNCs were immortalized by lentiviral hTERT gene delivery (hTERT-682TL and hTERT-779TL), they did not form any detectable masses, even in the most sensitive neonate NOG mouse platform. Moreover, the hTERT-ahMNCs had no gross chromosomal abnormalities on a karyotype analysis. Taken together, our data suggest that neonate NOG mice could be a sensitive animal platform to test tumorigenic potential of stem cell therapeutics and that ahMNCs could be a genetically stable stem cell source with little tumorigenic activity to develop regenerative treatments for neurodegenerative diseases.
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.|Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea.
authors.forename: Kee Hang
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea.|Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Nam
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.|Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea.
authors.forename: Da Eun
authors.initials: da E
authors.lastname: Jeong
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.|Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea.
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Seoul, South Korea.|Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Song
authors.affiliation: Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Seoul, South Korea.|Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea.
authors.forename: Hee Jang
authors.initials: HJ
authors.lastname: Pyeon
authors.affiliation: Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Kyeongjin
authors.initials: K
authors.lastname: Kang
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.|Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea.
authors.forename: Seung-Cheol
authors.initials: SC
authors.lastname: Hong
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea.|Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea.
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.|Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, Seoul, South Korea.|Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea.
authors.forename: Kyeung Min
authors.initials: KM
authors.lastname: Joo
mesh_terms: D000328:Adult; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D059785:Karyotype; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics; D055815:Young Adult
chemical_list: C509186:TERT protein, human; D019098:Telomerase