Adult mesenchymal stem cells support cisplatin-treated dorsal root ganglion survival.
Mesenchymal stem cells (MSCs) have been found to be useful in the management of different models of neurological diseases. In the present study, we tested the possible protective effect of MSCs on sensory dorsal root ganglia (DRG) explants exposed to the toxic effect of CDDP, a widely used anticancer drug. DRG explants cultured on a collagen layer and exposed to NGF for 2h (differentiating neurons) or for 5 days (fully differentiated neurons) were treated with CDDP and subsequently co-cultured with MSCs. MSCs were able to support the survival of both differentiating and fully differentiated DRG neurons up to 2 months after the drug treatment, reducing the CDDP-induced death of DRG neurons. MSCs were, however, unable to restore the correct length of DRG neurites compromised by CDDP treatment. The positive effect on neuronal survival was exerted through the contact between DRG and MSCs, and not mediated by neurotrophic factors released by the MSCs. Our observations could represent a starting point for designing a neuroprotective strategy to limit CDDP induced neuropathy without interfering with its anticancer properties.
Scuteri
Arianna
A
Dipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-Bicocca, Via Cadore 48, 20052 Monza, Italy. arianna.scuteri@unimib.it
Donzelli
Elisabetta
E
Ravasi
Maddalena
M
Tredici
Giovanni
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D018920:Coculture Techniques; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D009924:Organ Culture Techniques; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D000970:Antineoplastic Agents; D005904:Glial Fibrillary Acidic Protein; D010751:Phosphopyruvate Hydratase; D002945:Cisplatin