Fetal porcine ventral mesencephalon graft. Determination of the optimal gestational age for implantation in parkinsonian patients.
Human fetal ventral mesencephalon tissue has been used as dopaminergic striatal implants in Parkinsonian patients, so far with variable effects. Fetuses from animals that breed in large litters, e.g., pigs, have been considered as alternative donors of dopaminergic tissue. The optimal gestational age of the porcine fetal donors has not been studied systematically. We collected ventral mesencephalic (VM) tissue from fetal pigs, embryonal ages E21, E28, E42, and E70, and examined the viability of the fetal VM cells after dissociation, the expression of tyrosine hydroxylase (TH) in culture, the presence of catecholamines, and the cellular survival and outgrowth up to 10 months after intrastriatal implantation in rats. The highest viability was found in suspensions prepared from E28 fetuses. The highest number of TH-positive cells was found in cell cultures prepared from E28 VM tissue. Explants with a gestational age of 28 and 42 days contained the largest amount of dopamine. Only E28-derived grafts showed TH-cell survival after implantation in rat striatum. Our results show that a gestational age of 28 days must be considered to be the optimal age for dopaminergic tissue derived from pig fetuses for therapeutic use as intrastriatal grafts in Parkinsonian patients.
HogenEsch
R I
RI
Department of Neurology, University Hospital Groningen, The Netherlands.
Koopmans
J
J
Copray
J C
JC
van Roon
W M
WM
Kema
I
I
Molenaar
G
G
Go
K G
KG
Staal
M J
MJ
D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods* / Q000592:standards; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004298:Dopamine / Q000032:analysis / Q000502:physiology; D005260:Female; D016332:Fetal Tissue Transplantation / Q000379:methods* / Q000592:standards; D005865:Gestational Age; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D008636:Mesencephalon / Q000166:cytology / Q000637:transplantation*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D010300:Parkinson Disease / Q000503:physiopathology / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013552:Swine; D014183:Transplantation, Heterologous; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine