title: Transplantation of novel human GDF5-expressing CHO cells is neuroprotective in models of Parkinson's disease.
abstract: Growth/differentiation factor 5 (GDF5) is a neurotrophic factor that promotes the survival of midbrain dopaminergic neurons in vitro and in vivo and as such is potentially useful in the treatment of Parkinson's disease (PD). This study shows that a continuous supply of GDF5, produced by transplanted GDF5-overexpressing CHO cells in vivo, has neuroprotective and neurorestorative effects on midbrain dopaminergic neurons following 6-hydroxydopamine (6-OHDA)-induced lesions of the adult rat nigrostriatal pathway. It also increases the survival and improves the function of transplanted embryonic dopaminergic neurons in the 6-OHDA-lesioned rat model of PD. This study provides the first proof-of-principle that sustained delivery of GDF5 in vivo may be useful in the treatment of PD.
authors.affiliation: Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Costello
authors.forename: Gerard W
authors.initials: GW
authors.lastname: O'Keeffe
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Hurley
authors.forename: Aideen M
authors.initials: AM
authors.lastname: Sullivan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002470:Cell Survival; D006224:Cricetinae; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000166:cytology / Q000637:transplantation; D005260:Female; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D055428:Growth Differentiation Factor 5 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology / Q000637:transplantation*; D015999:Multivariate Analysis; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D016627:Oxidopamine / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D016627:Oxidopamine