Autologous bone marrow stromal cells (BMSCs) offer significant practical 
advantages for potential clinical applications in multiple sclerosis (MS). Based 
on recent experimental data, a number of clinical trials have been designed for 
the intravenous (IV) and/or intrathecal (ITH) administration of BMSCs in MS 
patients. Delivery of BMSCs in the cerebrospinal fluid via 
intracerebroventricular (ICV) transplantation is a useful tool to identify 
mechanisms underlying the migration and function of these cells. In the current 
study, BMSCs were ICV administered in severe and mild EAE, as well as naive 
animals; neural precursor cells (NPCs) served as cellular controls. Our data 
indicated that ICV-transplanted BMSCs significantly ameliorated mild though not 
severe EAE. Moreover, BMSCs exerted significant anti-inflammatory effect on 
spinal cord with concomitant reduced axonopathy only in the mild EAE model. 
BMSCs migrated into the brain parenchyma and, depending on their cellular 
density, within brain parenchyma formed cellular masses characterized by focal 
inflammation, demyelination, axonal loss and increased collagen-fibronectin 
deposition. These masses were present in 64% of ICV BMASC-transplanted severe 
EAE animals whereas neither BMSCs transplanted in mild EAE cases nor the NPCs 
exhibited similar behavior. BMSCs possibly exerted their fibrogenic effect via 
both paracrine and autocrine manner, at least partly due to up-regulation of 
connective tissue growth factor (CTGF) under the trigger of TGFb1. Our findings 
are of substantial relevance for clinical trials in MS, particularly regarding 
the possibility that ICV transplanted BMSCs entering the inflamed central 
nervous system may exhibit - under conditions - a local pathology of yet unknown 
consequences.