Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury.
Studies demonstrating the versatility of neural progenitor cells (NPCs) have recently rekindled interest in neurotransplantation methods aimed at treating traumatic brain injury (TBI). However, few studies have evaluated the safety and functional efficacy of transplanted NPCs beyond a few months. The purpose of this study was to assess the long-term survival, migration, differentiation and functional significance of NPCs transplanted into a mouse model of TBI out to 1 year post-transplant. NPCs were derived from E14.5 mouse brains containing a transgene-expressing green fluorescent protein (GFP) and cultured as neurospheres in FGF2-containing medium. Neurospheres were injected into the ipsilateral striatum of adult C57BL/6 mice 1 week following unilateral cortical impact injury. Behavioral testing revealed significant improvements in motor abilities in NPC-treated mice as early as 1 week, and the recovery was sustained out to 1 year post-transplant. In addition, mice receiving NPC transplants showed significant improvement in spatial learning abilities at 3 months and 1 year, whereas an intermediate treatment effect on this behavioral parameter was detected at 1 month. At 14 months post-transplant, GFP(+) NPCs were observed throughout the injured hippocampus and adjacent cortical regions of transplanted brains. Immunohistochemical analysis revealed that the majority of transplanted cells co-labeled for NG2, an oligodendrocyte progenitor cell marker, but not for neuronal, astrocytic or microglial markers. In conclusion, transplanted NPCs survive in the host brain up to 14 months, migrate to the site of injury, enhance motor and cognitive recovery, and may play a role in trophic support following TBI.
Department of Psychology, Emory University, Atlanta, GA 30322, USA.
Deborah A
DA
Shear
Matthew C
MC
Tate
David R
DR
Archer
Stuart W
SW
Hoffman
Verne D
VD
Hulce
Michelle C
MC
Laplaca
Donald G
DG
Stein
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000941:Antigens / Q000378:metabolism; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D007839:Functional Laterality / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000637:transplantation*; D009687:Nuclear Proteins / Q000378:metabolism; D011247:Pregnancy; D011509:Proteoglycans / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000502:physiology*; D013995:Time; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D000941:Antigens; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D016900:Neurofilament Proteins; D009687:Nuclear Proteins; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4