Functional recovery after simultaneous transplantation with neuro-epithelial stem cells and adjacent mesenchymal tissues into infarcted rat brain.
BACKGROUND
Cerebral infarction results in impairment of motor and cognitive functions. We performed intracranial transplantation of multipotential neuro-epithelial stem cells with mesenchyme into experimentally large ischemic lesions to study their potential to relieve deficits.


METHODS
Wistar albino rats were subjected to transient middle cerebral artery occlusion for 60 minutes, producing an extensive ischemic lesion in the ipsilateral striatum and adjacent cerebral cortex. The rat mesencephalic neural plate at the early somite stage (embryonic day 10.5) together with adjacent ventral mesenchyme was used as donor material. We performed histological and immunohistochemical studies, with antibodies against tyrosine hydroxylase, and dopamine- and adenosine 3': 5'-monophosphate-regulated phosphoprotein 32 (DARPP-32; a striatal marker). Micro-angiograms were made by using Microfil silicone rubber. Morris Water-maze learning and treadmill task were employed to evaluate motor and cognitive functions.


RESULTS
A viable non-tumoral mass was recognized in the rat striatum, up to as long as 156 days after transplantation. There were many cells positive for tyrosine hydroxylase or DARPP-32 in the graft. Some of the DARPP-32 positive cells within the graft had extended their dendrites into host tissues. In the micro-angiograms, many fine vessels were observed within the graft and dilated vessels meandered around the graft. Transplanted animals recovered significantly better in motor and cognitive functions than animals injected with only culture medium.


CONCLUSIONS
Neuro-epithelial stem cells may follow several lines of differentiation; along the naturally genetically programmed line of differentiation, or along other cell lines depending on different environments. Grafting of neuro-epithelial stem cells with mesenchyme may merit a further study as a treatment for cerebral infarction.
Fukunaga
A
A
Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan. fukunaga@sc.itc.keio.ac.jp
Kawase
T
T
Uchida
K
K
D000818:Animals; D002545:Brain Ischemia; D002544:Cerebral Infarction / Q000628:therapy*; D003072:Cognition Disorders / Q000209:etiology / Q000628:therapy; D004847:Epithelial Cells / Q000637:transplantation; D007150:Immunohistochemistry; D018782:Maze Learning; D009420:Nervous System / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation / Q000379:methods* / Q000662:veterinary; D016896:Treatment Outcome