The positive effect of adult undifferentiated mesenchymal stem cells (MSCs) on neuronal survival has already been reported, although the mechanisms by which MSCs exert their effect are still a matter of debate. Here we have demonstrated that MSCs are able to prolong the survival of dorsal root ganglion (DRG) neurons mainly by inhibiting some proteolytic enzymes, and in particular the pathway of metalloproteinases (MMPs), a family of proteins that are involved in many neuronal processes, including survival. The inhibition of MMPs was both direct, by acting on MT-MMP1, and indirect, by acting on those proteins that regulate MMPs' activation, such as Timp-1 and Sparc. The importance of the MMPs' down-regulation for neuronal survival was also demonstrated by using N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycyl hydroxamic acid (NNGH), a wide range inhibitor of metalloproteinases, which was able to increase the survival of DRG neurons in a significant manner. The down-regulation of MMPs, obtained both by MSC contact and by chemical inhibition, led to the inactivation of caspase 3, the executor of apoptotic death in DRG neurons cultured alone, while caspase 7 was found to be irrelevant for the apoptotic process. The capacity of MSCs to prevent apoptosis mainly by inactivating the metalloproteinase pathway is an important finding that sheds light on MSCs' mechanism of action, making undifferentiated MSCs a promising tool for the treatment of many different neurodegenerative pathologies.

Scuteri, A., Ravasi, M., Pasini, S., Bossi, M., Tredici, G. (2011). Mesenchymal stem cells support dorsal root ganglion neurons survival by inhibiting the metalloproteinase pathway. NEUROSCIENCE, 172, 12-19 [10.1016/j.neuroscience.2010.10.065].

Mesenchymal stem cells support dorsal root ganglion neurons survival by inhibiting the metalloproteinase pathway

SCUTERI, ARIANNA;RAVASI, MADDALENA;PASINI, SILVIA;BOSSI, MARIO;TREDICI, GIOVANNI
2011

Abstract

The positive effect of adult undifferentiated mesenchymal stem cells (MSCs) on neuronal survival has already been reported, although the mechanisms by which MSCs exert their effect are still a matter of debate. Here we have demonstrated that MSCs are able to prolong the survival of dorsal root ganglion (DRG) neurons mainly by inhibiting some proteolytic enzymes, and in particular the pathway of metalloproteinases (MMPs), a family of proteins that are involved in many neuronal processes, including survival. The inhibition of MMPs was both direct, by acting on MT-MMP1, and indirect, by acting on those proteins that regulate MMPs' activation, such as Timp-1 and Sparc. The importance of the MMPs' down-regulation for neuronal survival was also demonstrated by using N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycyl hydroxamic acid (NNGH), a wide range inhibitor of metalloproteinases, which was able to increase the survival of DRG neurons in a significant manner. The down-regulation of MMPs, obtained both by MSC contact and by chemical inhibition, led to the inactivation of caspase 3, the executor of apoptotic death in DRG neurons cultured alone, while caspase 7 was found to be irrelevant for the apoptotic process. The capacity of MSCs to prevent apoptosis mainly by inactivating the metalloproteinase pathway is an important finding that sheds light on MSCs' mechanism of action, making undifferentiated MSCs a promising tool for the treatment of many different neurodegenerative pathologies.
Articolo in rivista - Articolo scientifico
Coculture Techniques; Hydroxamic Acids; Metalloproteases; Cells, Cultured; Female; Rats; Sulfonamides; Animals; Mesenchymal Stem Cells; Apoptosis Regulatory Proteins; Rats, Sprague-Dawley; Cell Communication; Cell Survival; Signal Transduction; Ganglia, Spinal; Sensory Receptor Cells; Neural Pathways; Protease Inhibitors
English
2011
172
12
19
none
Scuteri, A., Ravasi, M., Pasini, S., Bossi, M., Tredici, G. (2011). Mesenchymal stem cells support dorsal root ganglion neurons survival by inhibiting the metalloproteinase pathway. NEUROSCIENCE, 172, 12-19 [10.1016/j.neuroscience.2010.10.065].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/38229
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