title: The co-injection of somatic cells with embryonic stem cells affects teratoma formation and the properties of teratoma-derived stem cell-like cells.
abstract: The aim of this study was to assess the biological reactions triggered by stem cell transplantation related to phenotypic alteration, host-to-cell response, chromosomal stability, transcriptional alteration, and stem cell-like cell re-expansion. B6CBAF1 mouse embryonic stem cells (ESCs) were injected subcutaneously into homologous or heterologous (B6D2F1) recipients, and heterologous injections were performed with or without co-injection of B6D2F1 fetal fibroblasts. All homologous injections resulted in teratoma formation, whereas a sharp decrease in formation was detected after heterologous injection (100 vs. 14%; p<0.05). The co-injection of somatic cells in heterologous injections enhanced teratoma formation significantly (14 vs. 75%; p<0.05). Next, ESC-like cell colonies with the same genotype as parental ESCs were formed by culturing teratoma-dissociated cells. Compared with parental ESCs, teratoma-derived ESC-like cells exhibited significantly increased aneuploidy, regardless of homologous or heterologous injections. Repopulation of the parental ESCs was the main factor that induced chromosomal instability, whereas the co-injection of somatic cells did not restore chromosomal normality. Different genes were expressed in the parental ESCs and teratoma-derived ESC-like cells; the difference was larger with parental vs. heterologous than parental vs. homologous co-injections. The co-injection of somatic cells decreased this difference further. In conclusion, the host-to-cell interactions triggered by ESC transplantation could be modulated by co-injection with somatic cells. A mouse model using homologous or heterologous transplantation of stem cells could help monitor cell adaptability and gene expression after injection.
authors.affiliation: Major in Biomodulation and Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea; Department of Marine Bio-materials and Aquaculture, Pukyong National University, Busan, Korea.
authors.forename: Seung Pyo
authors.initials: SP
authors.lastname: Gong
authors.affiliation: Major in Biomodulation and Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea.
authors.forename: Boyun
authors.initials: B
authors.lastname: Kim
authors.affiliation: Major in Biomodulation and Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea.
authors.forename: Hyo Sook
authors.initials: HS
authors.lastname: Kwon
authors.affiliation: Major in Biomodulation and Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea.
authors.forename: Woo Sub
authors.initials: WS
authors.lastname: Yang
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, United States of America.
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Jeong
authors.affiliation: Major in Biomodulation and Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea.
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Major in Biomodulation and Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea; Research Institute for Agriculture and Life Science, Seoul, Korea.
authors.forename: Jeong Mook
authors.initials: JM
authors.lastname: Lim
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D033481:Chromosomes, Mammalian / Q000378:metabolism; D016000:Cluster Analysis; D053595:Embryonic Stem Cells / Q000166:cytology*; D005260:Female; D020869:Gene Expression Profiling; D063990:Gene Ontology; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D058977:Molecular Sequence Annotation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation; D013724:Teratoma / Q000473:pathology*
chemical_list: D012333:RNA, Messenger