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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

Mouse Purkinje cells stain for human Golgi Zone within the cerebellum of Naïve/experimental autoimmune encephalomyelitis (EAE)-mice treated with intravenous human mesenchymal stem cells (MSCs). Immunofluorescence photographs (a), (b) and (c) refer to dashed areas a, b, c in image (C). A cerebellum section from an EAE-mouse treated with intra-venous human MSCs immunologically labelled with human Golgi Zone (A) (red) and Calbindin-D28K (B) (green) and, merged images (C). (D) A diagram of a typical and complete area of a sagittally sectioned mouse cerebellum in which the presence of human MSCs was investigated and numerated.
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fig03: Mouse Purkinje cells stain for human Golgi Zone within the cerebellum of Naïve/experimental autoimmune encephalomyelitis (EAE)-mice treated with intravenous human mesenchymal stem cells (MSCs). Immunofluorescence photographs (a), (b) and (c) refer to dashed areas a, b, c in image (C). A cerebellum section from an EAE-mouse treated with intra-venous human MSCs immunologically labelled with human Golgi Zone (A) (red) and Calbindin-D28K (B) (green) and, merged images (C). (D) A diagram of a typical and complete area of a sagittally sectioned mouse cerebellum in which the presence of human MSCs was investigated and numerated.

Mentions: Analysis of cerebellar sections from both naïve and EAE mice infusion revealed the presence of mouse Purkinje cells, expressing Calbindin-D28K, co-expressing human Golgi Zone within the Purkinje cell layer of the cerebellum of animals 22 days post intra-venous injection of MSC (Figure 3).


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)

Mouse Purkinje cells stain for human Golgi Zone within the cerebellum of Naïve/experimental autoimmune encephalomyelitis (EAE)-mice treated with intravenous human mesenchymal stem cells (MSCs). Immunofluorescence photographs (a), (b) and (c) refer to dashed areas a, b, c in image (C). A cerebellum section from an EAE-mouse treated with intra-venous human MSCs immunologically labelled with human Golgi Zone (A) (red) and Calbindin-D28K (B) (green) and, merged images (C). (D) A diagram of a typical and complete area of a sagittally sectioned mouse cerebellum in which the presence of human MSCs was investigated and numerated.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig03: Mouse Purkinje cells stain for human Golgi Zone within the cerebellum of Naïve/experimental autoimmune encephalomyelitis (EAE)-mice treated with intravenous human mesenchymal stem cells (MSCs). Immunofluorescence photographs (a), (b) and (c) refer to dashed areas a, b, c in image (C). A cerebellum section from an EAE-mouse treated with intra-venous human MSCs immunologically labelled with human Golgi Zone (A) (red) and Calbindin-D28K (B) (green) and, merged images (C). (D) A diagram of a typical and complete area of a sagittally sectioned mouse cerebellum in which the presence of human MSCs was investigated and numerated.
Mentions: Analysis of cerebellar sections from both naïve and EAE mice infusion revealed the presence of mouse Purkinje cells, expressing Calbindin-D28K, co-expressing human Golgi Zone within the Purkinje cell layer of the cerebellum of animals 22 days post intra-venous injection of MSC (Figure 3).

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