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American Society for Experimental Neurotherapeutics Abstracts
February 2003

What Has Fetal Transplantation Taught Us About Cellular Transplantation Into the CNS?

Arch Neurol. 2003;60(2):295-296. doi:10.1001/archneur.60.2.295-a

The clinical trials with transplantation of brain tissue from aborted human fetuses in patients with Parkinson disease (PD), and to some extent in patients with Huntington disease, provide proof-of-principle for the cell replacement strategy in the human brain. In PD, for which clinical cell therapy research has reached the furthest, intrastriatal grafts of mesencephalic tissue can reinnervate the striatum, restore dopamine release and movement-related frontal cortical activation, and give rise to significant clinical improvement. However, it is unlikely that transplantation of human fetal tissue can be developed into therapies for large numbers of patients owing to the poor availability of tissue for grafting and problems with standardization, purity, and viability. Stem cells from different sources could be useful to generate almost unlimited numbers of specific neuron types (eg, dopamine neurons for PD). Most importantly, the clinical trials, as well as studies in animal models, have taught us which requirements have to be fulfilled for a graft to induce marked and clinically valuable improvement in patients with PD. (1) The grafted cells have to express the complete cellular machinery for dopamine synthesis and release and possess the properties of fully mature mesencephalic dopamine neurons, both morphologically and electrophysiologically; (2) at least 100 000 grafted dopamine neurons should survive long-term in each putamen; (3) the grafted dopamine neurons should reestablish a dense, functional, dopamine-releasing terminal network in large parts of the striatum; (4) the grafts have to become functionally integrated into host basal ganglia-thalamo-cortical circuitries; and (5) when tested preclinically in animal models of PD, the cells must be able to reverse functional deficits resembling the symptoms in patients. Thus, the biological problems that have to be solved to develop stem cell–based therapies for brain diseases are complex and should not be underestimated.

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