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Fusion between human mesenchymal stem cells and rodent cerebellar Purkinje cells.

Kemp K, Gordon D, Wraith DC, Mallam E, Hartfield E, Uney J, Wilkins A, Scolding N - Neuropathol. Appl. Neurobiol. (2011)

Bottom Line: 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. 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.

View Article: PubMed Central - PubMed

Affiliation: Multiple Sclerosis and Stem Cell Group, Institute of Clinical Neurosciences, UK. kevin.kemp@bristol.ac.uk

ABSTRACT

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.

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Related in: MedlinePlus

An increase in mouse Purkinje cells expressing human Golgi Zone in experimental autoimmune encephalomyelitis (EAE) vs. naïve mice treated with intra-venous human MSCs. (A) Quantification of Purkinje cells co-expressing human Golgi Zone in naïve mice (n = 5) and EAE mice (n = 5) 22 days post MSC infusion (**P < 0.01). (B) Quantification of the mean number of Purkinje cells per random field within the cerebellum of EAE and naïve mice (n = 5) 22 days post MSC infusion.
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fig04: An increase in mouse Purkinje cells expressing human Golgi Zone in experimental autoimmune encephalomyelitis (EAE) vs. naïve mice treated with intra-venous human MSCs. (A) Quantification of Purkinje cells co-expressing human Golgi Zone in naïve mice (n = 5) and EAE mice (n = 5) 22 days post MSC infusion (**P < 0.01). (B) Quantification of the mean number of Purkinje cells per random field within the cerebellum of EAE and naïve mice (n = 5) 22 days post MSC infusion.

Mentions: To investigate whether the induction of EAE increases the levels of cellular fusion and heterokaryon formation within the mouse cerebellum, the numbers of human Golgi Zone/Calbindin-D28K positive mouse Purkinje cells from naïve and EAE mice were determined. Immunolabelled sagittal sections of the cerebellum were examined and numbers of human Golgi/Calbindin-D28K double positive cells and total numbers of Calbindin-D28K positive cells were determined [10 complete sagittal sections of the cerebellum (Figure 3D) from five animals/treatment were investigated]. Within naïve animals a frequency of 0.147 ± 0.046% of Purkinje cells were positive for human Golgi Zone, compared with the significantly higher level of 1.454 ± 0.629% evident within the EAE group (P < 0.01) (Figure 4A). There were no differences in the number of Purkinje cells per random field counted within the cerebellum of EAE versus naïve animals 22 days post infusion with MSC (Figure 4B).


Fusion between human mesenchymal stem cells and rodent cerebellar Purkinje cells.

Kemp K, Gordon D, Wraith DC, Mallam E, Hartfield E, Uney J, Wilkins A, Scolding N - Neuropathol. Appl. Neurobiol. (2011)

An increase in mouse Purkinje cells expressing human Golgi Zone in experimental autoimmune encephalomyelitis (EAE) vs. naïve mice treated with intra-venous human MSCs. (A) Quantification of Purkinje cells co-expressing human Golgi Zone in naïve mice (n = 5) and EAE mice (n = 5) 22 days post MSC infusion (**P < 0.01). (B) Quantification of the mean number of Purkinje cells per random field within the cerebellum of EAE and naïve mice (n = 5) 22 days post MSC infusion.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150530&req=5

fig04: An increase in mouse Purkinje cells expressing human Golgi Zone in experimental autoimmune encephalomyelitis (EAE) vs. naïve mice treated with intra-venous human MSCs. (A) Quantification of Purkinje cells co-expressing human Golgi Zone in naïve mice (n = 5) and EAE mice (n = 5) 22 days post MSC infusion (**P < 0.01). (B) Quantification of the mean number of Purkinje cells per random field within the cerebellum of EAE and naïve mice (n = 5) 22 days post MSC infusion.
Mentions: To investigate whether the induction of EAE increases the levels of cellular fusion and heterokaryon formation within the mouse cerebellum, the numbers of human Golgi Zone/Calbindin-D28K positive mouse Purkinje cells from naïve and EAE mice were determined. Immunolabelled sagittal sections of the cerebellum were examined and numbers of human Golgi/Calbindin-D28K double positive cells and total numbers of Calbindin-D28K positive cells were determined [10 complete sagittal sections of the cerebellum (Figure 3D) from five animals/treatment were investigated]. Within naïve animals a frequency of 0.147 ± 0.046% of Purkinje cells were positive for human Golgi Zone, compared with the significantly higher level of 1.454 ± 0.629% evident within the EAE group (P < 0.01) (Figure 4A). There were no differences in the number of Purkinje cells per random field counted within the cerebellum of EAE versus naïve animals 22 days post infusion with MSC (Figure 4B).

Bottom Line: 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. 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.

View Article: PubMed Central - PubMed

Affiliation: Multiple Sclerosis and Stem Cell Group, Institute of Clinical Neurosciences, UK. kevin.kemp@bristol.ac.uk

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus