Direct neuronal and macroglial versus indirect macrophagic labeling in transplants of fetal neural tissue incubated with gold particles

Abstract

In a recent light microscopic study based on the transplantation of fetal cells previously incubated with gold-loaded Sendai viruses, S. C. Ardizzoni, A. Michaels, and G. W. Arendash (1988, Science 239: 635-637) proposed that fetal neurons could migrate out into an adult host brain. This result was puzzling in view of several previous contradictory studies, and the light microscopic identification of labeled cells as neurons could be questioned. The present study was therefore undertaken to replicate this study but using electron microscopy to definitely identify migrating gold-labeled elements. Analysis was performed in a model of thalamic transplantation in which previous labeling studies, using thymidine or horseradish peroxidase, had failed to demonstrate any neuronal migration. Gold particles combined with wheat germ agglutinin peroxidase were used to label the fetal tissue prior to transplantation. Fetal cells did incorporate the protein gold complex, and the gold particles were visualized in transplants up to at least 2.5 months after grafting. Electron microscopy analysis reveals that the gold particles are internalized and retained in the lysosomes of grafted neurons and glial cells. In no transplant could labeled grafted neurons be observed intermingled with host neurons, outside the limits of the transplant. In contrast, heavily labeled macrophages were observed surrounding the transplants and sometimes migrating away from the transplant-host interface into the host tissue. These macrophages, presumably of host origin, can be recognized at the light microscopic level by their yellowish staining, a cellular characteristic already noted by Ardizzoni et al. for gold-labeled migrating elements.