Human amniotic epithelial cells produce dopamine and survive after implantation into the striatum of a rat model of Parkinson's disease: a potential source of donor for transplantation therapy.
We have recently found that human amniotic epithelial (HAE) cells synthesize catecholamines including dopamine (DA). The present study was designed to explore the possibility of HAE cells to serve as a donor for transplantation therapy of Parkinson's disease (PD). Thus, we investigated their ability to produce DA in vitro and the survival and function of HAE cells grafted into a rat model of PD. RT-PCR and Western blotting revealed that HAE cells express tyrosine hydroxylase (TH) mRNA and protein, respectively. TH-immunohistochemistry on cultured HAE cells demonstrated that around 10% of the total cells are immunopositive for this protein. The production of DA by HAE cells was increased with time in the presence of L-tyrosine and BH(4), and was abolished with a specific TH inhibitor, alpha-methyl-rho-tyrosine. Dissociated HAE cells transduced with the Escherichia coli LacZ marker gene (beta-gal) were implanted into the previously DA-depleted striatum of immunosuppressed rats. Two weeks postgrafting HAE grafts were demonstrated to survive without overgrowth, as evidenced by the presence of beta-gal-positive cells and TH-immunoreactive cells within the grafts. The grafts also provided partial amelioration of apomorphine-induced rotational asymmetry. The results clearly indicate that HAE cells capable of producing DA can survive and function in the brain of a rat model of PD. Although DA replacement therapy of PD could possibly be achieved with implantation of HAE cells, further studies are needed to develop strategies to enhance the ability of HAE cells to produce DA as well as the graft survival.
Kakishita
K
K
Department of Neurological Surgery, Wakayama Medical College, Wakayama, Japan.
Elwan
M A
MA
Nakao
N
N
Itakura
T
T
Sakuragawa
N
N
D000653:Amniotic Fluid / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D002470:Cell Survival; D017690:Cell Transplantation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D005260:Female; D006801:Humans; D010300:Parkinson Disease / Q000523:psychology / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior; D014019:Tissue Donors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine