Transplantation of hNT neurons into the ischemic cortex: cell survival and effect on sensorimotor behavior.
Cell transplantation offers a potential new treatment for stroke. Animal studies using models that produce ischemic damage in both the striatum and the frontal cortex have shown beneficial effects when hNT cells (postmitotic immature neurons) were transplanted into the ischemic striatum. In this study, we investigated the effect of hNT cells in a model of stroke in which the striatum remains intact and damage is restricted to the cortex. hNT cells were transplanted into the ischemic cortex 1 week after stroke induced by distal middle cerebral artery occlusion (dMCAo). The cells exhibited robust survival at 4 weeks posttransplant even at the lesion border. hNT cells did not migrate, but they did extend long neurites into the surrounding parenchyma mainly through the white matter. Neurite extension was predominantly toward the lesion in ischemic animals but was bidirectional in uninjured animals. Extension of neurites through the cortex toward the lesion was also seen when there was some surviving cortical tissue between the graft and the infarct. Prolonged deficits were obtained in four tests of sensory-motor function. hNT-transplanted animals showed a significant improvement in functional recovery on one motor test, but there was no effect on the other three tests relative to control animals. Thus, despite clear evidence of graft survival and neurite extension, the functional benefit of hNT cells after ischemia is not guaranteed. Functional benefit could depend on other variables, such as infarct location, whether the cells mature, the behavioral tests employed, rehabilitation training, or as yet unidentified factors.
Department of Neurosurgery, Stanford University, Stanford, California, USA. tbliss1@stanford.edu
T M
TM
Bliss
S
S
Kelly
A K
AK
Shah
W C
WC
Foo
P
P
Kohli
C
C
Stokes
G H
GH
Sun
M
M
Ma
J
J
Masel
S R
SR
Kleppner
T
T
Schallert
T
T
Palmer
G K
GK
Steinberg
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery*; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D017690:Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D011187:Posture / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors