To the editor—In the August issue of Nature Neuroscience, Studer and coworkers presented an interesting paper describing transplants of expanded mesencephalic precursors in Parkinsonian rats1. In keeping with earlier findings2, they demonstrate that neuronal precursors from embryonic mesencephalon can be expanded in the presence of basic fibroblast growth factor, and that a significant proportion (about 18%) of these neuroblasts differentiate into dopaminergic neurons after withdrawal of the growth factor. Studer et al. also uniquely demonstrate that these neurons can survive intracerebral transplantation and reverse a behavioral deficit in hemiparkinsonian rats. Although they suggest that the expansion of mesencephalic dopaminergic neurons can reduce the amount of donor tissue needed in grafting experiments, we feel there is need for caution. Earlier studies have shown that, without any neuroprotective treatment, typically 3000–5000 dopaminergic neurons survive grafting from the mesencephalon of one rat embryo (for example, Refs 3,4), which is equivalent to a survival rate of around 10%. Studer et al. obtain around 110,000 mesencephalic cells from each embryo, which then undergo a 10-fold proliferation, similar to that previously reported. Single spheres of differentiating neurons are cultured starting with 200,000 proliferated cells (less than 1/5 of one embryo starting material). Each transplant recipient then received a mean of 6–7 spheres, equivalent to about one embryo starting material, and exhibited a mean of 1221 surviving grafted dopaminergic neurons. Thus, even after the proliferation step, the survival per embryo is clearly less than when transplanting the tissue directly without an intervening proliferation step. Indeed, according to their own calculations they lose as many as 95–97% of the differentiated dopaminergic neurons in the grafting step. This does not in any way diminish the importance of the findings demonstrating expansion of dopaminergic neurons, but highlights that future studies must attempt to reduce the death of such cells during their differentiation and subsequent transplantation, possibly by the administration of growth factors or antioxidants3,4,5. Only when there is a actual gain in the numbers of surviving dopaminergic neurons from one embryo can such a technique be truly valuable in clinical trials.

See “Reply to 'Survival of expanded dopaminergic precursors is critical for clinical trials' ” by Studer et al.