Effects of implantation site of stem cell grafts on behavioral recovery from stroke damage.
OBJECTIVE
Findings that MHP36 stem cells grafted into intact parenchyma contralateral to the lesion induced by middle cerebral artery occlusion promoted recovery from stroke deficits led us to investigate whether implantation site of stem cells affects the functional efficacy of MHP36 grafts.


METHODS
MHP36 cells (200 000/8 microL) were implanted in the left (n=8) or right (n=9) parenchyma or infused into the right ventricle (intraventricular; n=7) 2 to 3 weeks after stroke induced by 60 minutes of intraluminal right middle cerebral artery occlusion. Additionally, intact (n=11) and stroke (n=7) control groups were tested for 14 weeks in bilateral asymmetry, rotation bias, and spatial learning tasks before histological investigation of cell distribution and differentiation.


RESULTS
Rats with left and right parenchymal grafts showed reduced bilateral asymmetry but no improvement in spatial learning. Conversely, spatial learning improved in rats with intraventricular grafts, but marked asymmetry persisted. No grafted group showed reduced amphetamine-induced rotation bias or reduced lesion volume relative to stroke controls. In all grafted groups, cells occupied both sides of the brain. A third of cells grafted in the striatum crossed the midline to occupy homologous regions in intact and lesioned hemispheres and differentiated into site-appropriate phenotypes.


CONCLUSIONS
After stroke, both the intact and lesioned hemispheres attract grafted stem cells, suggesting repair processes that utilize cells both for local repair and to augment plastic changes in contralateral motor pathways. However, differential effects of parenchymal and intraventricular grafts suggest that different mechanisms are implicated in recovery from cognitive and sensorimotor deficits induced by stroke.
Modo
Michel
M
Psychology Department, Institute of Psychiatry, London, England. m.modo@iop.kcl.ac.uk
Stroemer
R Paul
RP
Tang
Ellen
E
Patel
Sara
S
Hodges
Helen
H
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001522:Behavior, Animal; D002452:Cell Count; D002454:Cell Differentiation; D002460:Cell Line; D002552:Cerebral Ventricles; D004195:Disease Models, Animal; D006085:Graft Survival; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology / Q000628:therapy; D018782:Maze Learning; D009043:Motor Activity; D009474:Neurons / Q000166:cytology; D009928:Organ Specificity; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012399:Rotation; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D020521:Stroke / Q000150:complications / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
D000943:Antigens, Differentiation