PubMed · 5897130
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H W Boschann, W Tittler. 1965. [Labor induction by amniotomy under amnioscopic control].. https://doi.org/10.1007/bf00672186
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We recently found that human amniotic epithelial (HAE) cells secrete biologically active neurotrophins such as brain-derived neurotrophic factor and neurotrophin-3, both of which exhibit trophic activities on dopamine (DA) neurons. The present study explored whether implantation of HAE cells can be a possible means to deliver trophic factors into the brain to prevent the death of DA neurons in a rat model of Parkinson's disease. We first investigated the ability of HAE cells to produce factors capable of promoting DA cell survival in vitro, and then tested whether HAE cell grafts survive and prevent the death of nigral DA neurons in rats with 6-hydroxydopamine lesions. A treatment with conditioned medium derived from HAE cell cultures enhanced the survival of tyrosine hydroxylase (TH)-immunopositive DA cells in serum-free cultures. The conditioned medium also protected the morphological integrity of TH-positive neurons against toxic insult with 6-hydroxydopamine. HAE cells were grafted into the midbrain of immunosuppressed rats. The rats were then subjected to a unilateral nigrostriatal lesion induced by intrastriatal infusions of 6-hydroxydopamine. HAE cell transplants were found to survive without evidence for overgrowth 2 weeks postgrafting. The number of nigral DA cells, detected with either TH-immunohistochemistry or retrograde labelling with fluorogold, was significantly increased in rats given the grafts as compared to that in control animals without the grafts. The results indicate that HAE cells produce diffusible molecules that can enhance the survival of DA neurons. Although the factors that contribute to the currently observed effects remain to be fully determined, implantation of HAE cells could be a viable strategy to counteract the loss of DA neurons in Parkinson's disease.
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In this study, we employed RT-PCR and radioligand binding studies to evaluate the gene expression and binding characteristics, respectively, of dopamine D(1) receptors in human amniotic epithelial cells (HAEC). The results showed that HAEC natively expressed D(1) receptor mRNA, as measured by RT-PCR, which was identical to that of human brain. Saturation binding studies using [(3)H]SCH 23390 demonstrated the presence of a high affinity D(1) site in HAEC with K(D) and B(max) values of 2.01+/-0.25 nM and 32.5+/-3.7 fmol/mg protein, respectively. Competition studies showed that selective D(1) antagonists were potent displacers of [(3)H]SCH 23390 binding with a potency order consistent with D(1) receptor characteristics. The current results present compelling evidence that HAEC natively express D(1) receptor mRNA and binding sites. The results also establish a primate cell model that can possibly be used for studying D(1) receptor signal transduction and molecular mechanisms and exploring newly developed drugs acting at these receptors.