Human neural stem cell transplants improve motor function in a rat model of Huntington's disease.
The present study investigated the neuroanatomical and behavioral effects of human stem cell transplants into the striatum of quinolinic acid (QA)-lesioned rats. Twenty-four rats received unilateral QA (200 nM/microl) injections into the striatum. One week later, rats were transplanted with stem cells derived from human fetal cortex (12 weeks postconception) that were either 1) pretreated in culture media with the differentiating cytokine ciliary neurotrophic factor (CNTF; n = 9) or 2) allowed to grow in culture media alone (n=7). Each rat was injected with a total of 200,000 cells. A third group of rats (n=8) was given a sham injection of vehicle. Rats transplanted with human stem cells performed significantly better over the 8 weeks of testing on the cylinder test compared with those treated with vehicle (P < or = 0.001). Stereological striatal volume analyses performed on Nissl-stained sections revealed that rats transplanted with CNTF-treated neurospheres had a 22% greater striatal volume on the lesioned side compared with those receiving transplants of untreated neurospheres (P = 0.0003) and a 26% greater striatal volume compared with rats injected with vehicle (P < or = 0.0001). Numerous human nuclei-positive cells were visualized in the striatum in both transplantation groups. Grafted cells were also observed in the globus pallidus, entopeduncular nucleus, and substantia nigra pars reticulata, areas of the basal ganglia receiving striatal projections. Some of the human nuclei-positive cells coexpressed glial fibrillary acidic protein and NeuN, suggesting that they had differentiated into neurons and astrocytes. Taken together, these data demonstrate that striatal transplants of human fetal stem cells elicit behavioral and anatomical recovery in a rodent model of Huntington's disease.
McBride
Jodi L
JL
Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA.
Behrstock
Soshana P
SP
Chen
Er-Yun
EY
Jakel
Rebekah J
RJ
Siegel
Irwin
I
Svendsen
Clive N
CN
Kordower
Jeffrey H
JH
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000637:transplantation; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology; D003342:Corpus Striatum / Q000254:growth & development / Q000473:pathology / Q000601:surgery; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009068:Movement / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D017378:Quinolinic Acid; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D014183:Transplantation, Heterologous / Q000379:methods*; D016896:Treatment Outcome
D020934:Ciliary Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D017378:Quinolinic Acid