Xenografting of fetal pig ventral mesencephalon corrects motor asymmetry in the rat model of Parkinson's disease.
A suspension of cells from embryonic day 21 fetal pig ventral mesencephalon was transplanted into the striatum of 20 immunosuppressed rats with 6-hydroxydopamine-induced lesions of the nigrostriatal dopamine pathway. Of these rats, 15 showed reduction of amphetamine-induced ipsilateral rotation by 9 weeks and complete reversal of rotation by 14-17 weeks. Animals maintained stable reversal of rotations (contralateral direction) until cessation of Cyclosporin A (CyA) treatment at 15-20 weeks. Within 4-9 weeks after CyA removal, these rats showed exclusively ipsilateral rotations during behavioral testing which were comparable to pre-transplant levels, suggesting that the grafts were rejected upon cessation of CyA treatment. Rats were sacrificed and tyrosine hydroxylase (TH) immunohistochemistry was performed at several time points, both on and off CyA, to examine a possible correlation between the degree of rotational behavior and the number of TH-positive surviving grafted cells. Staining showed large numbers (230-12,329) of TH-positive surviving cells in animals displaying a high degree of rotational correction (1.6 to -9.6 net ipsilateral rotations/min) after cessation of CyA treatment. Two control groups, those transplanted with non-neuronal cells from the pig ventral mesencephalon (n = 5) and those receiving only daily CyA injections (n = 4) showed no significant reduction of net ipsilateral rotations throughout the experiment. No TH-positive surviving cells were seen in the one non-neuronal transplant analyzed. This data demonstrates long-term retention of xenografted tissue with immunosuppression and its concomitant restoration of normal motor behavior in the rat model of Parkinson's disease.
Huffaker
T K
TK
Hana Biologics, Inc., Alameda, CA 94501.
Boss
B D
BD
Morgan
A S
AS
Neff
N T
NT
Strecker
R E
RE
Spence
M S
MS
Miao
R
R
D000818:Animals; D002452:Cell Count; D003524:Cyclosporins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection / Q000187:drug effects; D006892:Hydroxydopamines; D007150:Immunohistochemistry; D008636:Mesencephalon / Q000196:embryology / Q000637:transplantation*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000601:surgery*; D051381:Rats; D011919:Rats, Inbred Strains; D012399:Rotation; D013552:Swine; D014183:Transplantation, Heterologous; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D003524:Cyclosporins; D006892:Hydroxydopamines; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase