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 synthesiz e catecholamines including dopamine (DA). The present study was designed to explore the possibility of HAE cells to serve as a donor for transplantati on 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-immun ohistochemistry on cultured HAE cells demonstrated that around 10% of the t otal cells are immunopositive for this protein. The production of DA by HAE cells was increased with time in the presence of L-tyrosine and BH4, and w as abolished with a specific TH inhibitor, alpha-methyl-rho-tyrosine. Disso ciated HAE cells transduced with the Escherichia coil LacZ marker gene (bet a-gal) were implanted into the previously DA-depleted striatum of immunosup pressed rats. Two weeks postgrafting HAE grafts were demonstrated to surviv e without overgrowth, as evidenced by the presence of beta-gal-positive cel ls and TH-immunoreactive cells within the grafts. The grafts also provided partial amelioration of apomorphine-induced rotational asymmetry. The resul ts 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 s tudies are needed to develop strategies to enhance the ability of HAE cells to produce DA as well as the graft survival. (C) 2000 Academic Press.