Limits...
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.

Show MeSH

Related in: MedlinePlus

Anti-human Golgi Zone binds specifically to human mesenchymal stem cell (MSC) and not rodent cells. Images are of rat E18 cerebellar neuronal (A/B) and human MSC (C/D) cultures co-labelled with human Golgi Zone (red), βIII tubulin (green) and Hoescht nuclear stain (blue) (A&C are images of respective negative controls using no primary antibodies).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4150530&req=5

fig02: Anti-human Golgi Zone binds specifically to human mesenchymal stem cell (MSC) and not rodent cells. Images are of rat E18 cerebellar neuronal (A/B) and human MSC (C/D) cultures co-labelled with human Golgi Zone (red), βIII tubulin (green) and Hoescht nuclear stain (blue) (A&C are images of respective negative controls using no primary antibodies).

Mentions: A human specific anti-human Golgi Zone monoclonal antibody was used to detect human-derived cells post intra-venous MSC infusion in mice. The human Golgi Zone antibody specificity to cells of human origin was tested on both human derived MSC and rodent cerebellar neuronal cultures (Figure 2). Using this antibody, Golgi staining was completely absent within cerebellar cells of rodent origin. However, 100% of MSCs were positive for the Golgi Zone marker (Figure 2). Human Golgi Zone staining was also absent when tested on cerebellar tissue sections derived from control mice that had not received an infusion of MSC (data not shown).


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)

Anti-human Golgi Zone binds specifically to human mesenchymal stem cell (MSC) and not rodent cells. Images are of rat E18 cerebellar neuronal (A/B) and human MSC (C/D) cultures co-labelled with human Golgi Zone (red), βIII tubulin (green) and Hoescht nuclear stain (blue) (A&C are images of respective negative controls using no primary antibodies).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Anti-human Golgi Zone binds specifically to human mesenchymal stem cell (MSC) and not rodent cells. Images are of rat E18 cerebellar neuronal (A/B) and human MSC (C/D) cultures co-labelled with human Golgi Zone (red), βIII tubulin (green) and Hoescht nuclear stain (blue) (A&C are images of respective negative controls using no primary antibodies).
Mentions: A human specific anti-human Golgi Zone monoclonal antibody was used to detect human-derived cells post intra-venous MSC infusion in mice. The human Golgi Zone antibody specificity to cells of human origin was tested on both human derived MSC and rodent cerebellar neuronal cultures (Figure 2). Using this antibody, Golgi staining was completely absent within cerebellar cells of rodent origin. However, 100% of MSCs were positive for the Golgi Zone marker (Figure 2). Human Golgi Zone staining was also absent when tested on cerebellar tissue sections derived from control mice that had not received an infusion of MSC (data not shown).

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