Mesencephalic human neural progenitor cells transplanted into the adult hemiparkinsonian rat striatum lack dopaminergic differentiation but improve motor behavior.

Abstract:  The clinical outcome of cell replacement therapies depends upon the successful survival and differentiation of transplanted cells. Here, we transplanted human neural progenitor cells derived from the ventral mesencephalon of an 8-week-old embryo into the ipsilateral (right) striatum of unilateral 6-hydroxydopamine-le sioned adult rats. To assess the therapeutic potency of grafted cells, 2 independent behavioral tests were conducted 12 weeks after transplantation: in the rotation test, a mild behavioral improvement was detected, and in the cylinder test, transplanted animals overcame the lesion-induced right forepaw preference. To address this behavioral improvement to a dopaminergic differentiation capacity of transplanted cells in vivo, immunohistochemistry for tyrosine hydroxylase was performed, showing a total lack of immunoreactivity. However, we found a considerable number of transplanted human nuclei-positive cells preferentially differentiated into neurons. In addition, glial fibrillary acidic protein-expressing cells were also detected. Our results show that behavioral improvement does not necessarily correlate with a differentiation of transplanted precursors into dopaminergic neurons, indicating other factors to be involved in a partial functional recovery. Nevertheless, for the development of a clinically useful cell therapy, it is important to overcome obstacles, namely the poor dopaminergic differentiation of human neural progenitor cells after grafting.