The induction of a peripheral neuropathy is a very common side effect of many chemotherapeutic agents, including platinum compounds, and it often represents the dose limiting factor for drug clinical use. Several strategies have been suggested to reduce drug neurotoxicity without affecting the antineoplastic potential, but up to now results were not encouraging. Recently, it has been demonstrated that Mesenchymal Stem Cells (MSCs) are able to promote the survival and the maturation of untreated sensory neurons of dorsal root ganglia (DRG), which represent also the target of drug neurotoxicity. Aim of this work is to verify the neuroprotective potential of MSCs on rat DRG exposed to cisplatin (CDDP), a chemotherapeutic and neurotoxic agent. DRG post-mitotic explants from E15 rat embryos were exposed for 24 hours to different cisplatin concentrations. After 24 hours, medium was changed and DRG were directly co-cultured with human MSCs (hMSCs) or with hMSCs conditioned medium (hMSC-CM). DRG explants were photographed every day up to 1 month, and the longest neurite of each DRG was measured to evaluate neurotoxicity. DRG survival was estimated by measuring the death area percentage. The survival of CDDP-treated DRG was increased after the co-cultures with hMSCs, and both hMSCs and hMSC-CM were able to improve the neurite outgrowth of untreated and CDDP-treated DRG after 48 hours. This MSC-dependent increase of neurite length was however no longer evident at later times (1 month). This effect on neurite elongation was probably mediated by CSPG, MAG and Nogo, some proteins involved in the modulation of neurite elongation, which resulted expressed and released in the culture medium of hMSCS. Our results demonstrated a neuroprotective effect of hMSCs on CDDP toxicity and evidenced the ability of these cells to modulate neurite elongation. In this way MSCs could represent a possible mean to limit the neurotoxicity on DRG which arises after cisplatin therapy.
Ravasi, M., Maggioni, D., Milano, A., Monfrini, M., Donzelli, E., Foudah, D., et al. (2012). Human Mesenchymal Stem Cells protection on Cisplatin treated Dorsal Root Ganglia. In 11th International Symposium on Platinum Coordination Compounds in Cancer Chemotherapy Abstract Book.
|Citazione:||Ravasi, M., Maggioni, D., Milano, A., Monfrini, M., Donzelli, E., Foudah, D., et al. (2012). Human Mesenchymal Stem Cells protection on Cisplatin treated Dorsal Root Ganglia. In 11th International Symposium on Platinum Coordination Compounds in Cancer Chemotherapy Abstract Book.|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||No|
|Titolo:||Human Mesenchymal Stem Cells protection on Cisplatin treated Dorsal Root Ganglia|
|Autori:||Ravasi, M; Maggioni, D; Milano, A; Monfrini, M; Donzelli, E; Foudah, D; D’Amico, G; Miloso, M; Scuteri, A; Tredici, G|
RAVASI, MADDALENA (Primo)
MAGGIONI, DANIELE (Secondo)
SCUTERI, ARIANNA (Penultimo)
TREDICI, GIOVANNI (Corresponding)
|Data di pubblicazione:||2012|
|Nome del convegno:||11th International Symposium on Platinum Coordination Compounds in Cancer Chemotherapy|
|Appare nelle tipologie:||02 - Intervento a convegno|