Cell fusion in the brain: two cells forward, one cell back

Abstract

Adult stem cell populations, notably those which reside in the bone marrow, have been shown to contribute to several neuronal cell types in the rodent and human brain. The observation that circulating bone marrow cells can migrate into the central nervous system and fuse with, in particular, cerebellar Purkinje cells has suggested, at least in part, a potential mechanism behind this process. Experimentally, the incidence of cell fusion in the brain is enhanced with age, radiation exposure, inflammation, chemotherapeutic drugs and even selective damage to the neurons themselves. The presence of cell fusion, shown by detection of increased bi-nucleated neurons, has also been described in a variety of human central nervous system diseases, including both multiple sclerosis and Alzheimer’s disease. Accumulating evidence is therefore raising new questions into the biological significance of cell fusion, with the possibility that it represents an important means of cell-mediated neuroprotection or rescue of highly complex neurons that cannot be replaced in adult life. Here, we discuss the evidence behind this phenomenon in the rodent and human brain, with a focus on the subsequent research investigating the physiological mechanisms of cell fusion underlying this process. We also highlight how these studies offer new insights into endogenous neuronal repair, opening new exciting avenues for potential therapeutic interventions against neurodegeneration and brain injury.

Long-Term Outcome of Administration of c-kit POS Cardiac Progenitor Cells After Acute Myocardial Infarction

“…It is unlikely that the Y-chromosome POS cells were the result of fusion of transplanted CPCs with endogenous cells, such as myocytes, because fusion would be expected to produce binucleated cells of size comparable to the original cells and fusion events are rare (<1:10 4 –10 5 cells 33, 34 ); in contrast, the Y-chromosome POS cells we observed were very small, mononucleated, and relatively frequent (Fig. 6A–D).…”

Mechanisms and consequences of aneuploidy and chromosome instability in the aging brain

“…This phenomenon is also observed in the brain, where bone marrow-derived cells (BMDCs) are shown to fuse with Purkinje cells with a frequency increasing with age (Lapham, 1968; Nern et al, 2009). Fusion is believed to rescue injured neuronal cells that cannot undergo cell division bycontributing genetic material from BM to restore tissue homeostasis (Kemp et al, 2014) (see also Section 7).…”

“…Bi-nucleated neurons have been described in a variety of human CNS pathologies, including AD, neuro-Behcet's disease, multiple sclerosis, Kuru, and spino olivo-ponto-cerebello-nigral atrophy (Kemp et al, 2014). In the case of AD it has been proposed that neuronal death is the consequence of an abortive cell cycle, possibly with intermediate tetraploid cells.…”

Up-regulation of syncytin-1 contributes to TNF-α-enhanced fusion between OSCC and HUVECs partly via Wnt/β-catenin-dependent pathway

“…More and more studies have demonstrated the association of chronic inflammation and cancer. Recent discoveries of a much broader role of cell fusion in tissue homeostasis and regeneration2124252627, particularly during inflammatory conditions112829, have aroused our great interest to investigate the inflammation as one of the possible driving forces of cancer/host cells fusion. In the present study, we found that the distance between nuclei was varied in different hybrid cells, which may be related to the time point that fusion occurs; We also noticed that the spontaneous fusion between oral SCC-9 and HUVEC was as low as 0.7%~0.8%.…”