Transplantation of neuronal and glial precursors dramatically improves sensorimotor function but not cognitive function in the traumatically injured brain.
Embryonic stem (ES) cells have been investigated in various animal models of neurodegenerative disease; however, few studies have examined the ability of ES cells to improve functional outcome following traumatic brain injury (TBI). The purpose of the present study was to examine the ability of pre-differentiated murine ES cells (neuronal and glial precursors) to improve functional outcome. Rats were prepared with a unilateral controlled cortical impact injury or sham and then transplanted 7 days later with 100K ES cells (WW6G) (~30% neurons) or media. Two days following transplantation rats were tested on a battery of behavioral tests. It was found that transplantation of ES cells improved behavioral outcome by reducing the initial magnitude of the deficit on the bilateral tactile removal and locomotor placing tests. ES cells also induced almost complete recovery on the vibrissae --> forelimb placing test, whereas, media-transplanted rats failed to show recovery. Acquisition of a reference memory task in the Morris water maze was not improved by transplantation of ES cells. Histological analysis revealed a large number of surviving ES cells in the lesion cavity and showed migration of ES cells into subcortical structures. It was found that transplantation of ES cells prevented the occurrence of multiple small necrotic cavities that were seen in the cortex adjacent to the lesion cavity in media transplanted rats. Additionally, ES cells transplants also significantly reduced lesion size. Results of this study suggest that ES cells that have been pre-differentiated into neuronal precursors prior to transplantation have therapeutic potential.
Brain Injury Laboratory, Department of Psychology and Program in Neuroscience, The Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA. hoenem@mail.ecu.edu
Michael R
MR
Hoane
G Daniel
GD
Becerra
J Elizabeth
JE
Shank
Lisa
L
Tatko
Elena S
ES
Pak
Michael
M
Smith
Alexander K
AK
Murashov
D000818:Animals; D001835:Body Weight; D001930:Brain Injuries / Q000601:surgery*; D016380:Brain Tissue Transplantation; D002454:Cell Differentiation; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000601:surgery*; D003213:Conditioning, Psychological; D005552:Forelimb / Q000502:physiology; D008297:Male; D051379:Mice; D009043:Motor Activity; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology; D009068:Movement; D009457:Neuroglia / Q000166:cytology; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D014110:Touch; D014738:Vibrissae / Q000294:innervation