Microtransplantation of whole ganglionic eminence cells ameliorates motor deficit, enlarges the volume of grafts, and prolongs survival in a rat model of Huntington's disease

Abstract

Studies have demonstrated that embryonic cell therapy is a potential approach for the treatment of Huntington's disease (HD). However, because of the limited resource of embryos, greater attention is needed in developing more efficient surgical techniques that not only enhance the therapy outcome but also avoid inefficient therapeutics of transplantation. In this study, we explored the curative effects of two different transplantation methods using a rat model of HD. Whole ganglionic eminence (WGE) cells or phosphate-buffered saline were transplanted into unilateral striatum of quinolinic acid (QA)-lesioned rats using microtransplantation instruments (with an outer diameter of 50 μm) or traditional transplantation instruments (with an outer diameter of 470 μm). Apomorphine-induced rotation test and adjusting step test were assessed after QA-induced lesion and 2, 4, 6, 8, 10, and 12 weeks after transplantation. The expression of neuronal nuclei (NeuN), dopamine, cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32), and glial fibrillary acidic protein (GFAP) was analyzed at 12 weeks after transplantation. We observed that microtransplanted rats performed better in the stepping test and had higher numbers of DARPP-32-positive cells compared with traditionally transplanted rats. Moreover, microtransplantation group showed lower GFAP expression surrounding the grafts in unilateral striatum and a higher survival rate posttransplantation compared with the traditional transplantation group. We conclude that microtransplantation is capable of enhancing therapeutic efficacy in the rat model of HD. This finding establishes the basis of an alternative transplantation strategy for treatment of HD.