Gong Seung Pyo, Kim Boyun, Kwon Hyo Sook, Yang Woo Sub, Jeong Jae-Wook, Ahn Jiyeon, Lim Jeong Mook
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.
Major in Biomodulation and Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea.
PLoS One. 2014 Sep 2;9(9):e105975. doi: 10.1371/journal.pone.0105975. eCollection 2014.
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.
本研究的目的是评估干细胞移植引发的与表型改变、宿主对细胞反应、染色体稳定性、转录改变以及干细胞样细胞再扩增相关的生物学反应。将B6CBAF1小鼠胚胎干细胞（ESCs）皮下注射到同源或异源（B6D2F1）受体中，异源注射时同时或不同时共注射B6D2F1胎儿成纤维细胞。所有同源注射均导致畸胎瘤形成，而异源注射后形成率急剧下降（100%对14%；p<0.05）。异源注射中共注射体细胞显著增强了畸胎瘤形成（14%对75%；p<0.05）。接下来，通过培养畸胎瘤解离细胞形成了与亲代ESCs具有相同基因型的ESC样细胞集落。与亲代ESCs相比，无论同源或异源注射，畸胎瘤来源的ESC样细胞均表现出明显增加的非整倍体。亲代ESCs的再增殖是诱导染色体不稳定的主要因素，而共注射体细胞并未恢复染色体正常状态。亲代ESCs和畸胎瘤来源的ESC样细胞中表达不同的基因；亲代与异源注射相比的差异大于亲代与同源共注射相比的差异。共注射体细胞进一步降低了这种差异。总之，ESC移植引发的宿主与细胞相互作用可通过与体细胞共注射来调节。使用干细胞同源或异源移植的小鼠模型有助于监测注射后细胞适应性和基因表达。
