Adjunctive use of the non-ionic surfactant Poloxamer 188 improves fetal dopaminergic cell survival and reinnervation in a neural transplantation strategy for Parkinson's disease.
Although neural transplantation of fetal dopaminergic cells is a promising therapy for Parkinson's disease, poor transplanted cell survival limits its efficacy. In the present study it was hypothesized that the use of Poloxamer 188 (P188), a non-ionic surfactant, during cell preparation and transplantation may protect cells from associated mechanical injury and thus improve transplanted cell survival in a rat model of Parkinson's disease. Fetal rat dopaminergic tissue was dissociated in media with or without P188 and then cultured for 1 week or transplanted into the striatum of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal dopaminergic pathway. Fetal dopaminergic cell survival and reinnervation of the host brain were examined using tyrosine hydroxylase immunohistochemistry and stereological quantification. The number of surviving tyrosine hydroxylase-immunoreactive cells in vitro and in vivo was significantly increased by 2.2-fold by incubating fetal dopaminergic cells with P188 during tissue dissociation. Furthermore, the striatal reinnervation in parkinsonian rats that received intrastriatal transplants of P188-exposed dopaminergic cells was significantly enhanced (1.8-fold increase) compared with rats that received non-P188-treated cells. In conclusion, P188 protects fetal dopaminergic cells from mechanical injury by increasing cell survival and enhances dopaminergic fibre outgrowth into the transplanted striatum. Use of P188 may thus be an important adjunct to improve the clinical efficacy of neural transplantation for Parkinson's disease.
Quinn
M
M
Cell Restoration Laboratory, Departments of Anatomy & Neurobiology and Surgery (Neurosurgery), Dalhousie University, Halifax, Nova Scotia, Canada.
Mukhida
K
K
Sadi
D
D
Hong
M
M
Mendez
I
I
D000661:Amphetamine; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D017690:Cell Transplantation / Q000379:methods*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors; D004622:Embryo, Mammalian; D005260:Female; D066298:In Vitro Techniques; D008636:Mesencephalon / Q000166:cytology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000503:physiopathology / Q000601:surgery*; D020442:Poloxamer / Q000494:pharmacology*; D051381:Rats; D013501:Surface-Active Agents / Q000494:pharmacology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; D013501:Surface-Active Agents; D020442:Poloxamer; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine