Survival, neuronal differentiation, and fiber outgrowth of propagated human neural precursor grafts in an animal model of Huntington's disease.
Expanded neural precursor cells provide an attractive alternative to primary fetal tissue for cell replacement therapies in neurodegenerative diseases. In this study we transplanted epigenetically propagated human neural precursor cells into a rat model of Huntington's disease. Neural precursors survived transplantation and large numbers differentiated to express neuronal antigens, including some that expressed DARPP-32, indicating a mature striatal phenotype had been adopted. Neuronal fibers from the grafts projected diffusely throughout the host brain, although there was no evidence that outgrowth was specifically target directed. This study supports the contention that propagated human neural precursors may ultimately be of use in therapeutic neural transplantation paradigms for diseases such as Huntington's disease.
Armstrong
R J
RJ
MRC Cambridge Centre for Brain Repair, University of Cambridge, UK. rjea100@cam.ac.uk
Watts
C
C
Svendsen
C N
CN
Dunnett
S B
SB
Rosser
A E
AE
D000110:Acetylcholinesterase / Q000032:analysis / Q000276:immunology; D000818:Animals; D000906:Antibodies; D016380:Brain Tissue Transplantation; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D016332:Fetal Tissue Transplantation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006085:Graft Survival; D006801:Humans; D006816:Huntington Disease / Q000601:surgery*; D009412:Nerve Fibers / Q000737:chemistry / Q000201:enzymology / Q000502:physiology*; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000637:transplantation* / Q000648:ultrastructure*; D010641:Phenotype; D010750:Phosphoproteins / Q000032:analysis / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D033581:Stem Cell Transplantation
D000906:Antibodies; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D000110:Acetylcholinesterase