Grafted neural progenitors migrate and form neurons after experimental traumatic brain injury.
OBJECTIVE
Neural stem and progenitor cells (NSPC) generate neurons and glia, a feature that makes them attractive for cell replacement therapies. However, efforts to transplant neural progenitors in animal models of brain injury typically result in high cell mortality and poor neuronal differentiation.


METHODS
In an attempt to improve the outcome for grafted NSPC after controlled cortical impact we transplanted Enhanced Green Fluorescent Protein (EGFP)-positive NSPC into the contra lateral ventricle of mice one week after injury.


RESULTS
Grafted EGFP-NSPC readily migrated to the injured hemisphere where we analyzed the proportion of progenitors and differentiated progeny at different time points. Transplantation directly into the injured parenchyma, resulted in few brains with detectable EGFP-NSPC. On the contrary, in more than 90% of the mice that received a transplant into the lateral ventricle detectable EGFP-positive cells were found. The cells were integrated into the lateral ventricle wall of the un-injured hemisphere, throughout the corpus callosum, and in the cortical perilesional area. At one-week post transplantation, grafted cells that had migrated to the perilesion area mainly expressed markers of neural progenitors and neurons, while in the corpus callosum and the ventricular lining, grafted cells with a glial fate were more abundant. After 3 months, grafted cells in the perilesion area were less abundant whereas cells that had migrated to the walls of the third- and lateral- ventricle of the injured hemisphere were still detectable, suggesting that the injury site remained a hostile environment.


CONCLUSIONS
Transplantation to the lateral ventricle, presumably for being a neurogenic region, provides a favorable environment improving the outcome for grafted NSPC both in term of their appearance at the cortical site of injury, and their acquisition of neural markers.
Wallenquist
U
U
Department of Medical Biochemistry and Microbiology, Uppsala University, Biomedical Center, Uppsala, Sweden.
Brännvall
K
K
Clausen
F
F
Lewén
A
A
Hillered
L
L
Forsberg-Nilsson
Karin
K
D000199:Actins / Q000235:genetics; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002452:Cell Count / Q000379:methods; D002465:Cell Movement / Q000502:physiology*; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000637:transplantation*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D007211:Indoles; D007381:Intermediate Filament Proteins / Q000378:metabolism; D020547:Lateral Ventricles / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism; D013997:Time Factors
D000199:Actins; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C007293:DAPI; D010751:Phosphopyruvate Hydratase