Grafts of adult subependymal zone neuronal progenitor cells rescue hemiparkinsonian behavioral decline.
Neuronal progenitor cells (NPCs) residing in the adult subependymal zone (SEZ) are a potential source of expandable cells for autologous transplantation to treat Parkinson's Disease and other types of brain injury. We have previously demonstrated the capacity of transplanted adult SEZ NPCs for heterotypic differentiation in the hippocampus. To further characterize the therapeutic potential of these cells, NPCs expanded from the adult rat SEZ were grafted to the striatum of normal and 6-OHDA lesioned adult rats. Grafted cells were assessed for neuronal differentiation, and lesioned animals were tested for amphetamine-induced rotational asymmetry. In addition, the effect of inducing differentiation in vitro prior to transplantation was assessed. Although grafted cells survived after 2 weeks in all animals, neither striatal deafferentation nor in vitro induction of differentiation resulted in significant neuronal differentiation of transplanted cells. Grafts, however, did produce a behavioral effect. While sham animals exhibited increased rotational behavior (+67%) from 2 to 4 weeks post-lesioning, grafted animals did not (-21%). Grafted cells continued to express nestin at the survival time point, and dopamine transporter (DAT) immunoreactivity was restored in the graft body. These results suggest that although neither the normal nor the deafferented striatum alone support the neuronal differentiation of transplanted adult SEZ NPCs, grafts maintaining a progenitor phenotype may produce a therapeutic benefit.
Richardson
R Mark
RM
Department of Neurosurgery, Medical College of Virginia Hospitals, Virginia Commonwealth University Health System, P.O. Box 980631, Richmond, VA 23298, USA.
Broaddus
William C
WC
Holloway
Kathryn L
KL
Fillmore
Helen L
HL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000378:metabolism / Q000601:surgery; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins; D004805:Ependyma / Q000166:cytology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007211:Indoles; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000166:cytology / Q000637:transplantation*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D010641:Phenotype; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D045442:Rotarod Performance Test / Q000379:methods; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; C493216:Slc6a3 protein, rat; D014404:Tubulin; D049452:Green Fluorescent Proteins; C007293:DAPI; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine