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.
Highlights
The transplantation of stem cells into living recipients causes several biological reactions in both the transplanted cells and recipient
Based on the biological events that occurred after transplantation, the primary aim was to examine the effects of co-injection of somatic cells with embryonic stem cells (ESCs) on cell engraftment
The results demonstrated that the coinjection of somatic cells with ESCs influenced host-to-cell adaptability, post-injection cell transformation and gene expression in re-expanded stem cell-like cells derived from neoplastic tissues
Summary
The transplantation of stem cells into living recipients causes several biological reactions in both the transplanted cells and recipient. The injected cells might trigger host-to-cell immune responses; the regulation of this reaction is essential for successful migration and homing after transplantation. The injected stem cells might respond unexpectedly to the unfamiliar microenvironment. Several reports have suggested that various cellular changes occur after exposure to different microenvironments [1,2,3,4], and that the host microenvironment stimulates cellular plasticity to generate both normal and cancer cell progenitors [5,6]. Genetic instability and an altered phenotype are common after transplantation [7,8]. Understanding all the events that accompany injection will contribute significantly to the development of clinically useful transplantation technologies and novel strategies for regenerative medicine
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