Transplantation of human fetal tissue from spontaneous abortions to a rodent model of Parkinson's disease.
The use of human fetal tissue from elective abortions for cell transplantation therapies has been the subject of considerable controversy. Because of concerns regarding the use of tissue from elective abortions, tissue from spontaneous abortions has been suggested as an alternate donor source. In the present study we have evaluated human fetal tissue from spontaneous abortions to assess its viability, growth potential, and functional expression. Viable cells (Grade I) from a donor (7 wk postconception) were transplanted as a suspension into the striatum of rats with unilateral 6-OHDA lesions of the nigrostriatal pathway. A second group of animals received solid grafts of tissue from a Grade I donor 14 wk postconception. Tissue from Grade II and III specimens were not sufficiently viable for transplantation. Locomotor responses were monitored over a period of 15 wk and revealed an amelioration of rotational asymmetry by animals that received tissue from the 7 wk donor. Animals receiving tissue from the 14 wk donor showed no functional improvement. We found numerous graft-derived tyrosine hydroxylase (TH) immunopositive neurons contained within the transplantation site, and a rich plexus of TH-immunopositive fibers extending into the striatum of animals receiving tissue from the 7 wk donor. Animals receiving tissue from the 14 wk donor exhibited tissue necrosis at the transplant site and were devoid of TH-immunopositive neurons. These results suggest that human fetal ventral mesencephalic cells from spontaneous abortions can survive and develop after transplantation, and rectify locomotor deficits associated with experimental parkinsonism if the donor tissue is of the appropriate gestational age at the time of implantation. Our study further suggests, however, that the availability of tissue from spontaneous abortions of sufficient viability is quite limited and may thus restrict its potential use in cell transplantation therapies for Parkinson's disease.
Kondoh
T
T
Department of Neurosurgery, University of Minnesota Medical School, Minneapolis 55455, USA.
Pundt
L L
LL
Blount
J P
JP
Conrad
J A
JA
Low
W C
WC
D000818:Animals; D016380:Brain Tissue Transplantation / Q000502:physiology*; D005260:Female; D016332:Fetal Tissue Transplantation; D006085:Graft Survival; D006801:Humans; D008297:Male; D008636:Mesencephalon; D009043:Motor Activity; D009412:Nerve Fibers / Q000201:enzymology; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000503:physiopathology / Q000628:therapy*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase