Cell Fusion-Mediated Tissue Regeneration as an Inducer of Polyploidy and Aneuploidy

Abstract

The biological phenomenon of cell fusion plays a crucial role in several physiological processes, including wound healing and tissue regeneration. Here, it is assumed that bone marrow-derived stem cells (BMSCs) could adopt the specific properties of a different organ by cell fusion, thereby restoring organ function. Cell fusion first results in the production of bi- or multinucleated hybrid cells, which either remain as heterokaryons or undergo ploidy reduction/heterokaryon-to-synkaryon transition (HST), thereby giving rise to mononucleated daughter cells. This process is characterized by a merging of the chromosomes from the previously discrete nuclei and their subsequent random segregation into daughter cells. Due to extra centrosomes concomitant with multipolar spindles, the ploidy reduction/HST could also be associated with chromosome missegregation and, hence, induction of aneuploidy, genomic instability, and even putative chromothripsis. However, while the majority of such hybrids die or become senescent, aneuploidy and genomic instability appear to be tolerated in hepatocytes, possibly for stress-related adaption processes. Likewise, cell fusion-induced aneuploidy and genomic instability could also lead to a malignant conversion of hybrid cells. This can occur during tissue regeneration mediated by BMSC fusion in chronically inflamed tissue, which is a cell fusion-friendly environment, but is also enriched for mutagenic reactive oxygen and nitrogen species.

Cell–Cell Fusion and the Roads to Novel Properties of Tumor Hybrid Cells

“…First of all, cell-cell fusion is a complex and tightly regulated process. Cells are not per se fusogenic, but have to enter a pro-fusogenic state first [1,4,6,7,9,77]. Likewise, hybridized cells have to return into a non-fusogenic state to prevent further uncontrolled fusion events.…”

Cell–cell fusion of mesenchymal cells with distinct differentiations triggers genomic and transcriptomic remodelling toward tumour aggressiveness

“…This transmission process has been widely described, notably in the fusion between cancer cells and leucocytes, where hybrid cells take advantage of the properties of the parents by inheriting both tumoral proliferation and leucocyte mobility properties, hence promoting metastatic dissemination 6 , 7 , 13 – 15 . Another consequence of cell–cell fusion is the acquisition of new properties which can be explained by the genomic and transcriptomic reshuffling that occurs in hybrid following a cell–cell fusion event 16 . Moreover, some studies have demonstrated that cell fusion can promote tumour initiation or participate in tumour relapse with the acquisition of drug resistance 6 , 17 – 20 .…”

制备人脐静脉内皮细胞和人肺腺癌细胞融合细胞的新方法

“…The biological phenomenon of cell fusion plays a crucial role in several physiological processes, including wound healing, tissue regeneration and tumor metastasis. 20 In recent years, 21 studies have shown that cell fusion can be spontaneous in the development of tumor. The fusion between tumor cells, as well as the fusion between tumor cells and host cells (such as macrophages, lymphocytes, endothelial cells, etc.…”