Embryonic stem cells promote motor recovery and affect inflammatory cell infiltration in spinal cord injured mice.
The purpose of this study was to determine the fate and the effects of undifferentiated embryonic stem cells (ESCs) in mice after contusive lesion of the spinal cord (SCI). Reproducible traumatic lesion to the cord was performed at T8 level by means of the Infinite Horizon Device, and was followed by intravenous injection of one million of undifferentiated ESCs through the tail vein within 2 h from the lesion. The ESCs-treated animals showed a significant improvement of the recovery of motor function 28 days after lesion, with an average score of 4.61+/-0.13 points of the Basso Mouse Scale (n=14), when compared to the average score of vehicle treated mice, 3.58+/-0.23 (n=10). The number of identified ESCs found at the lesion site was 0.6% of the injected cells at 1 week after transplantation, and further reduced to 0.04% at 1 month. It is, thus, apparent that the promoted hind-limb recovery cannot be correlated to a substitution of the lost tissue performed by the exogenous ESC. The extensive evaluation of production of several neuroprotective and inflammatory cytokines did not reveal any effect by ESC-treatment, but unexpectedly the number of invading macrophages and neutrophils was greatly reduced. This may explain the improved preservation of lesion site ventral myelin, at both 1 week (29+/-11%) and 1 month (106+/-14%) after injury. No teratoma formation was observed, although an inappropriate colonization of the sacral cord by differentiated nestin- and beta-tubulin III-positive ESCs was detected.
Bottai
Daniele
D
Department of Medicine, Surgery and Dentistry, Faculty of Medicine, University of Milan Via A. di Rudinì 8, 20142 Milan, Italy.
Cigognini
Daniela
D
Madaschi
Laura
L
Adami
Raffaella
R
Nicora
Emanuela
E
Menarini
Mauro
M
Di Giulio
Anna Maria
AM
Gorio
Alfredo
A
D000818:Animals; D000941:Antigens / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D005347:Fibroblasts / Q000166:cytology; D006085:Graft Survival / Q000276:immunology; D006614:Hindlimb / Q000294:innervation / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology; D009186:Myelin Sheath / Q000502:physiology; D009187:Myelitis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009504:Neutrophils / Q000276:immunology; D011509:Proteoglycans / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D014404:Tubulin / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D011509:Proteoglycans; D014404:Tubulin; D000099216:Chondroitin Sulfate Proteoglycan 4; C577485:Nes protein, mouse