Grafts of extra-adrenal chromaffin cells as aggregates show better survival rate and regenerative effects on parkinsonian rats than dispersed cell grafts.

The objective was to discern the neuroregenerative effect of grafts of extra-adrenal cells of the Zuckerkandl's paraganglion (ZP) in the nigrostriatal circuit, by using the retrograde model of parkinsonism in rats. The antiparkinsonian efficacy of two types of grafting procedures was studied (cell aggregates vs. dispersed cells), and GDNF and TGFbeta(1) (dopaminotrophic factors) as well as dopamine presence in extra-adrenal tissue was analyzed. Extra-adrenal chromaffin cells are noradrenergics, tissue dopamine is low, and they express both GDNF and TGFbeta(1). Grafts of cell aggregates, not of dispersed cells, exerted a trophic regeneration of the host striatum, leading to amelioration of motor deficits. Sprouting of spared dopaminergic fibers within the striatum, reduction of dopamine axon degeneration, and/or enhanced phenotypic expression of TH would explain striatal regeneration. Grafted cells as aggregates showed a better survival rate than dispersed cells, and they express higher levels of GDNF. Higher survivability and GDNF content together with the neurorestorative and dopaminotrophic action of both GDNF and TGFbeta(1) could account for striatal recovery and functional amelioration after grafting ZP cell aggregates. Finally, nigral degeneration and partial degeneration of ventral tegmental area were not precluded after transplantation, indicating that the trophic effect of grafts was local within the host striatum.

Adrenal chromaffin cells as transplants in animal models of Parkinson's disease.

The field of neural transplantation has moved rapidly forward in the last decade. Initially, fetal cells were used as implants to investigate their potential to ameliorate deficits in animal models of Parkinson's disease. However, because of the moral and legal problems associated with the use of fetal tissues in humans, alternative sources of donor tissue were sought which possessed the structural and functional characteristics needed to improve motor function in Parkinsonian patients. To date, one of the most promising tissues being investigated is the adrenal medulla, whose chromaffin cells possess an inherent plasticity of form and function. Transplanted chromaffin cells currently are being studied by a variety of approaches, including electron microscopy, in mouse, rat, and primate models of Parkinson's disease. An overview of the role of the chromaffin cell in this exciting and clinically important arena is briefly reviewed, with an emphasis on the fine structure of implanted chromaffin cells.