Intracarotid Infusion of Mesenchymal Stem Cells in an Animal Model of XXXX , Focusing on Cell Distribution and Neuroprotective and Behavioral Effects.

@entity2656 @entity146 @entity73 @entity16 @entity191 @entity51 @entity3826 @entity35 @entity2955 @entity528
Mesenchymal stem cells (MSCs) have been proposed as a potential therapeutic tool for @entity191 ( @entity191 ) 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, we evaluated homing of intraarterially infused @entity35 MSCs (rMSCs) in the brain of @entity35 bearing a @entity2955 ( @entity2955 )-induced lesion of the nigrostriatal tract, to establish whether the toxin-induced damage is sufficient to grant MSC passage across the blood-brain barrier (BBB) or if a transient BBB disruption is necessary. The rMSC distribution in peripheral organs and the effects of cell infusion on neurodegenerative process and @entity51 were also investigated. rMSCs were infused 14 days after @entity2955 injection. A hyperosmolar solution of @entity2656 was used to transiently permeabilize the BBB. @entity146 was assessed by adjusting step test and response to @entity3826 . Animals were sacrificed 7 and 28 days after cell infusion. Our work shows that appreciable delivery of rMSCs to the brain of @entity2955 -lesioned animals can be obtained only after @entity2656 pretreatment. A notable percentage of infused cells accumulated in peripheral organs. Infusion of rMSCs did not modify the progression of @entity2955 -induced @entity16 at the stepping test, but induced progressive normalization of the pathological response (contralateral turning) to @entity3826 administration. These findings suggest that many aspects should be further investigated before considering any translation of MSC systemic administration into the clinical setting for @entity191 treatment. SIGNIFICANCE: This study demonstrates that mesenchymal stem cells infused through the carotid artery do not efficiently cross the blood-brain barrier in @entity35 with a @entity528 , unless a permeabilizing agent (e.g., @entity2656 ) is used. The infusion did not reduce the @entity528 and associated @entity73 , but abolished the motor abnormalities these animals typically show when challenged with a dopaminergic agonist. Therefore, although arterially infused mesenchymal stem cells did not show neurorestorative effects in this study's @entity191 model, they appeared to normalize the pathological responsiveness of striatal neurons to dopaminergic stimulation. This capability should be further explored in future studies.
