title: IGF-I and bFGF improve dopamine neuron survival and behavioral outcome in parkinsonian rats receiving cultured human fetal tissue strands.
abstract: To promote dopamine cell survival in human fetal tissue strands transplanted into immunosuppressed 6-OHDA-lesioned rats, we have preincubated tissue in insulin-like growth factor-I (IGF-I, 150 ng/ml) and basic fibroblast growth factor (bFGF, 15 ng/ml) in vitro for 2 weeks. Growth factor treatment did not affect the rate of homovanillic acid production in vitro but increased overall dopamine neuron survival in animals after transplant from 1240 +/- 250 to 2380 +/- 440 neurons (P < 0.05). Animals in the growth factor-treated group had a significantly greater reduction in methamphetamine-induced rotation (66%) compared to control transplants (30%, P < 0.05). We conclude that in vitro preincubation of human fetal tissue strands with IGF-I and bFGF improves dopamine cell survival and the behavioral outcome of transplants.
authors.affiliation: US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, MCMR-UV-DB, Aberdeen Proving Grounds, Maryland 21010-5400, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Clarkson
authors.forename: W M
authors.initials: WM
authors.lastname: Zawada
authors.forename: K P
authors.initials: KP
authors.lastname: Bell
authors.forename: J E
authors.initials: JE
authors.lastname: Esplen
authors.forename: P K
authors.initials: PK
authors.lastname: Choi
authors.forename: K A
authors.initials: KA
authors.lastname: Heidenreich
authors.forename: C R
authors.initials: CR
authors.lastname: Freed
mesh_terms: D000028:Abortion, Induced; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D016380:Brain Tissue Transplantation / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000628:therapy*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D014183:Transplantation, Heterologous / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D016222:Fibroblast Growth Factor 2; D008694:Methamphetamine; D007334:Insulin-Like Growth Factor I; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine; D006719:Homovanillic Acid