Long-term survival of human central nervous system progenitor cells transplanted into a rat model of Parkinson's disease.
Progenitor cells were isolated from the developing human central nervous system (CNS), induced to divide using a combination of epidermal growth factor and fibroblast growth factor-2, and then transplanted into the striatum of adult rats with unilateral dopaminergic lesions. Large grafts were found at 2 weeks survival which contained many undifferentiated cells, some of which were migrating into the host striatum. However, by 20 weeks survival, only a thin strip of cells remained at the graft core while a large number of migrating astrocytes labeled with a human-specific antibody could be seen throughout the striatum. Fully differentiated graft-derived neurons, also labeled with a human-specific antibody, were seen close to the transplant site in some animals. A number of these neurons expressed tyrosine hydroxylase and were sufficient to partially ameliorate lesion-induced behavioral deficits in two animals. These results show that expanded populations of human CNS progenitor cells maintained in a proliferative state in culture can migrate and differentiate into both neurons and astrocytes following intracerebral grafting. As such these cells may have potential for development as an alternative source of tissue for neural transplantation in degenerative diseases.
Svendsen
C N
CN
MRC Cambridge Centre for Brain Repair, Cambridge University Forvie Site, United Kingdom. cns1000@hermes.cam.ac.uk
Caldwell
M A
MA
Shen
J
J
ter Borg
M G
MG
Rosser
A E
AE
Tyers
P
P
Karmiol
S
S
Dunnett
S B
SB
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000166:cytology; D016380:Brain Tissue Transplantation; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000473:pathology*; D004298:Dopamine / Q000032:analysis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016332:Fetal Tissue Transplantation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006085:Graft Survival; D006801:Humans; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D009836:Oligodendroglia / Q000166:cytology; D016627:Oxidopamine / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000473:pathology / Q000601:surgery*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine