The co-injection of somatic cells with embryonic stem cells affects teratoma formation and the properties of teratoma-derived stem cell-like cells.
The co-injection of somatic cells with embryonic stem cells affects teratoma formation and the properties of teratoma-derived stem cell-like cells.
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DOI：
10.1371/journal.pone.0105975
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lim JM
中科院分区：
文献类型：
--
作者：
Gong SP;Kim B;Kwon HS;Yang WS;Jeong JW;Ahn J;Lim JM
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、转录改变和干细胞样细胞再扩增相关的生物学反应。将B6 CBAF 1小鼠胚胎干细胞（ESC）皮下注射到同源或异源（B6 D2 F1）受体中，并在共注射或不共注射B6 D2 F1胎儿成纤维细胞的情况下进行异源注射。所有同源注射导致畸胎瘤形成，而异源注射后检测到形成的急剧减少（100对14%; p<0.05）。异源注射中体细胞的共注射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的细胞形成与亲本ESC具有相同基因型的ESC样细胞集落。与亲本胚胎干细胞相比，畸胎瘤衍生的胚胎干细胞样细胞表现出显着增加的非整倍体，无论同源或异源注射。亲代胚胎干细胞的再增殖是诱导染色体不稳定的主要因素，而体细胞的共注射不能恢复染色体正常。不同的基因在亲本ESC和畸胎瘤衍生的ESC样细胞中表达;亲本与异源的差异大于亲本与同源共注射的差异。体细胞的共注射进一步降低了这种差异。总之，ESC移植引发的宿主-细胞相互作用可以通过与体细胞共注射来调节。使用同源或异源干细胞移植的小鼠模型可以帮助监测注射后的细胞适应性和基因表达。
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.
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