IGF-I and bFGF improve dopamine neuron survival and behavioral outcome in parkinsonian rats receiving cultured human fetal tissue strands.
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.
Clarkson
E D
ED
US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, MCMR-UV-DB, Aberdeen Proving Grounds, Maryland 21010-5400, USA.
Zawada
W M
WM
Bell
K P
KP
Esplen
J E
JE
Choi
P K
PK
Heidenreich
K A
KA
Freed
C R
CR
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
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