Mesenchymal stemcells (MSCs) have been proposed as a potential therapeutic tool for Parkinson’s disease (PD) and systemic administration of these cells has been tested in preclinical and clinical studies. However, no information on survival and actual capacity of MSCs to reach the brain has been provided. In this study,weevaluatedhoming of intraarterially infused ratMSCs (rMSCs) in thebrain of rats bearing a 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal tract, to establishwhether the toxininduced damage is sufficient to grant MSC passage across the blood-brain barrier (BBB) or if a transient BBBdisruptionisnecessary.The rMSCdistributioninperipheralorgans and theeffects of cell infusionon neurodegenerative process andmotor deficitswere also investigated. rMSCswere infused 14 days after 6-OHDA injection. A hyperosmolar solution of mannitol was used to transiently permeabilize the BBB. Behavioralimpairmentwas assessedbyadjusting steptestandresponsetoapomorphine.Animalswere sacrificed 7 and 28 days after cell infusion. Our work shows that appreciable delivery of rMSCs to the brainof6-OHDA-lesionedanimalscanbeobtainedonlyaftermannitol pretreatment.Anotablepercentage of infused cells accumulated in peripheral organs. Infusion of rMSCs did notmodify the progression of 6-OHDA-induced damage or themotor impairment at the stepping test, but induced progressive normalization of the pathological response (contralateral turning) to apomorphine administration. These findings suggest thatmany aspects should be further investigated before considering any translation of MSC systemic administration into the clinical setting for PD treatment.
Intracarotid infusion of mesenchymal stem cells in an animal model of Parkinson’s disease, focusing on cell distribution and neuroprotective and behavioral effects
Cerri S.;Levandis G.;Ghezzi C.;Mangione A. S.;Blandini F.
2015-01-01
Abstract
Mesenchymal stemcells (MSCs) have been proposed as a potential therapeutic tool for Parkinson’s disease (PD) and systemic administration of these cells has been tested in preclinical and clinical studies. However, no information on survival and actual capacity of MSCs to reach the brain has been provided. In this study,weevaluatedhoming of intraarterially infused ratMSCs (rMSCs) in thebrain of rats bearing a 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal tract, to establishwhether the toxininduced damage is sufficient to grant MSC passage across the blood-brain barrier (BBB) or if a transient BBBdisruptionisnecessary.The rMSCdistributioninperipheralorgans and theeffects of cell infusionon neurodegenerative process andmotor deficitswere also investigated. rMSCswere infused 14 days after 6-OHDA injection. A hyperosmolar solution of mannitol was used to transiently permeabilize the BBB. Behavioralimpairmentwas assessedbyadjusting steptestandresponsetoapomorphine.Animalswere sacrificed 7 and 28 days after cell infusion. Our work shows that appreciable delivery of rMSCs to the brainof6-OHDA-lesionedanimalscanbeobtainedonlyaftermannitol pretreatment.Anotablepercentage of infused cells accumulated in peripheral organs. Infusion of rMSCs did notmodify the progression of 6-OHDA-induced damage or themotor impairment at the stepping test, but induced progressive normalization of the pathological response (contralateral turning) to apomorphine administration. These findings suggest thatmany aspects should be further investigated before considering any translation of MSC systemic administration into the clinical setting for PD treatment.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
