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Updated: Jun 9, 2026
Purification of Prominin-1+ Stem Cells from Postnatal Mouse Cerebellum
Published on: April 12, 2020
Fusion between human mesenchymal stem cells and rodent cerebellar Purkinje cells
1Multiple Sclerosis and Stem Cell Group, Institute of Clinical Neurosciences, UK. kevin.kemp@bristol.ac.uk
Aims:
we explored whether cellular fusion and heterokaryon formation between human and rodent cells in the cerebellum of mice occurs after intravenous injection of human bone marrow-derived mesenchymal stem cells (MSCs). The influence of central nervous system inflammation on this process was also assessed. In addition, we examined whether tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, factors associated with inflammation, increase cellular fusion between human MSCs and rodent cerebellar neurons in vitro.
Methods And Results:
human MSCs were intravenously injected into mice with experimental autoimmune encephalomyelitis (EAE) and control mice. After 22 days, mouse Purkinje cells expressing human Golgi Zone were found within the Purkinje cell layer of the cerebellum, indicating that fusion and heterokaryon formation had occurred. The numbers of heterokaryons in the cerebellum were markedly increased in mice with EAE compared with control mice. Rodent cerebellar neuronal cells labelled with enhanced green fluorescent proteinin vitro were co-cultured with human bone marrow-derived MSCs in the presence of TNF-alpha and/or IFN-gamma to determine their influence on fusion events. We found that fusion between MSCs and cerebellar neurons did occur in vitro and that the frequency of cellular fusion increased in the presence of TNF-alpha and/or IFN-gamma.
Conclusions:
we believe that this is the first paper to define fusion and heterokaryon formation between human MSCs and rodent cerebellar neurons in vivo. We have also demonstrated that fusion between these cell populations occurs in vitro. These findings indicate that MSCs may be potential therapeutic agents for cerebellar diseases, and other neuroinflammatory and neurodegenerative disorders.
Insights
Human mesenchymal stem cells (MSCs) fused with rodent cerebellar neurons in mice, especially during inflammation. This fusion also occurred in vitro, increasing with inflammatory factors, suggesting MSCs
Area of Science:
- Neuroscience
- Stem Cell Biology
- Immunology
Background:
- Mesenchymal stem cells (MSCs) are investigated for therapeutic potential in neurological disorders.
- Cellular fusion and heterokaryon formation are complex biological processes with implications for cell therapy.
- Neuroinflammation can significantly impact the behavior and integration of transplanted cells.
Purpose of the Study:
- To determine if human bone marrow-derived MSCs can fuse with rodent cerebellar cells in vivo.
- To assess the role of central nervous system inflammation in MSC-neuron fusion.
- To investigate the in vitro effect of inflammatory factors (TNF-alpha and IFN-gamma) on MSC-neuron fusion.
Main Methods:
- Intravenous injection of human MSCs into mice with experimental autoimmune encephalomyelitis (EAE) and control mice.
- Analysis of mouse cerebellum for human cell markers and heterokaryon formation.
- In vitro co-culture of rodent cerebellar neurons with human MSCs in the presence of TNF-alpha and/or IFN-gamma.
Main Results:
- Human Golgi Zone positive cells were identified within the mouse Purkinje cell layer, confirming in vivo fusion and heterokaryon formation.
- Heterokaryon numbers were significantly higher in EAE mice compared to controls, indicating inflammation enhances fusion.
- In vitro, human MSCs fused with rodent cerebellar neurons, with fusion frequency increasing in the presence of TNF-alpha and/or IFN-gamma.
Conclusions:
- This study provides the first evidence of in vivo fusion and heterokaryon formation between human MSCs and rodent cerebellar neurons.
- Cellular fusion between these cell types was also demonstrated in vitro, influenced by inflammatory mediators.
- These findings highlight the potential of MSCs as therapeutic agents for cerebellar diseases and other neuroinflammatory/neurodegenerative conditions.
