Intravenous administration of human neural stem cells induces functional recovery in Huntington's disease rat model.
An animal model induced by striatal quinolinic acid (QA) injection shows ongoing striatal degeneration mimicking Huntington's disease. To study the migratory ability and the neuroprotective effect of human neural stem cells (NSCs) in this model, we transplanted NSCs (5 x 10(6)) or saline intravenously at 7 days after unilateral QA injection. NSCs-group exhibited the reduced apomorphine-induced rotation and the reduced striatal atrophy compared to the control. PCR analysis for the human-specific ERV-3 gene supported an evidence of the engraftment of human NSCs in the rat brain. X-gal+ cells were found in and around the damaged striatum and migrated NSCs differentiated into neurons and glias. This result indicates that intravenously injected human NSCs can migrate into the striatal lesion, decrease the following striatal atrophy, and induce long-term functional improvement in a glutamate toxicity-induced striatal degeneration model.
Lee
Soon-Tae
ST
Department of Neurology, Clinical Research Institute, Seoul National University Hospital, 28, Yongon-Dong, Chongro-Gu, Seoul 110-744, South Korea.
Chu
Kon
K
Park
Jung-Eun
JE
Lee
Kyungmi
K
Kang
Lami
L
Kim
Seung U
SU
Kim
Manho
M
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D029721:Drosophila Proteins / Q000378:metabolism; D020077:Endogenous Retroviruses / Q000235:genetics; D007839:Functional Laterality; D005697:Galactosides; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000139:chemically induced / Q000628:therapy*; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D007262:Infusions, Intravenous / Q000379:methods*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D017378:Quinolinic Acid; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D045442:Rotarod Performance Test / Q000379:methods; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C109219:Brd protein, Drosophila; D004268:DNA-Binding Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D029721:Drosophila Proteins; D005697:Galactosides; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D010750:Phosphoproteins; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D010751:Phosphopyruvate Hydratase; D017378:Quinolinic Acid; D001058:Apomorphine; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside