Variable behavior and complications of autologous bone marrow mesenchymal stem cells transplanted in experimental autoimmune encephalomyelitis

Exp Neurol. 2011 Jul;230(1):78-89. doi: 10.1016/j.expneurol.2011.02.021. Epub 2011 Apr 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Area Under Curve
  • Brain / pathology
  • Cell Survival / drug effects
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / mortality
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / surgery*
  • Female
  • Gene Expression Regulation / drug effects
  • Green Fluorescent Proteins / genetics
  • Injections, Intraventricular / adverse effects
  • Interferon-gamma / metabolism
  • Mesenchymal Stem Cell Transplantation / adverse effects*
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Stem Cells / physiology
  • Neural Stem Cells / transplantation
  • Severity of Illness Index
  • Spinal Cord / pathology
  • Transforming Growth Factor beta / metabolism
  • Transplantation, Autologous / adverse effects
  • Tumor Necrosis Factor-alpha / metabolism


  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Green Fluorescent Proteins
  • Interferon-gamma