Effects of direct transplantation of multipotent mesenchymal stromal/stem cells into the demyelinated spinal cord.
The adult bone marrow contains a population of multipotent mesenchymal stromal cells (MSCs), defined by plastic adherence, expression of stromal cell surface markers, and differentiation into mesenchymal lineages. There has been much interest in the possible therapeutic use of MSCs in the treatment of demyelinating diseases of the central nervous system. One therapeutic possibility is that these cells may be able to remyelinate when directly injected into the demyelinated spinal cord. Here we examine the effects of direct transplantation of green fluorescent protein (GFP)-labeled MSCs into a model of focal spinal cord demyelination induced by ethidium bromide. We demonstrate that direct intralesional injection of undifferentiated MSCs does not lead to remyelination. Furthermore, we report that transplanted MSCs migrate into areas of normal tissue, deposit collagen, and are associated with axonal damage. These findings support the need for further experimental evaluation of the safety and efficacy of direct parenchymal injection of MSCs into demyelinated lesions and highlight an important issue regarding potential clinical consequences of culture heterogeneity of MSCs between centers.
Hunt
D P J
DP
Cambridge Centre for Brain Repair, Department of Clinical Neuroscience, Forvie Site, Addenbrookes Hospital, University of Cambridge, Cambridge, UK. dpjh2@cam.ac.uk
Irvine
K A
KA
Webber
D J
DJ
Compston
D A S
DA
Blakemore
W F
WF
Chandran
S
S
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003711:Demyelinating Diseases / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000473:pathology
D015415:Biomarkers; D049452:Green Fluorescent Proteins