Abstract
1309
Objectives: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a severe loss of dopaminergic neurons in substantia nigra pars compacta. Clinically available pharmacological modalities for PD fail to alleviate the neurodegeneration in dopaminergic system. Cell transplantation is considered as a potential therapy for PD. The transplantation of ventral mesencephalic (VM) tissue and induced pluripotent stem cell (iPSC)-derived dopaminergic neuron might restore the dopaminergic system of PD. However, the immune response induced by iPSC is poor understood. In this study, we evaluated the therapeutic effects of co-grafting iPSCs and VM tissue in Parkinsonian rats.
Methods: Parkinsonian rats were divided into four groups which respectively received following surgeries: sham, VM graft , iPSC graft, and co-graft of VM+iPSC. All rats were examined with apomorphine-induced rotation test and [18F]FE-PE2I/ animal-PET one week before graft surgery, as well as four and eight weeks after the transplantation, respectively. The specific uptake ratio (SUR) of [18F]FE-PE2I was calculated as mean counts per voxel of striatum minus mean counts per voxel of cerebellum then divided by mean counts per voxel of cerebellum, such as (striatum-cerebellum)/cerebellum. All rats were scarified and brains were harvested for the immunohistochemistry (IHC) analysis for tyrosine hydroxylase (TH) and dopamine transporter (DAT).
Results: The drug-induced rotation behaviors in VM graft and co-graft group were significantly improved after the transplantation, whereas no change was observed in sham and iPSC graft groups. The SUR of PET images revealed that the [18F]FE-PE2I uptakes in the grafted striatum of VM graft group and co-graft group were increased in four weeks after transplantation. Eight weeks after the transplantation, the [18F]FE-PE2I uptakes of VM group showed increased but the those of co-graft group were decreased. The results of IHC studies showed abundant TH and DAT positive cells found in the grafted striatum of VM graft group, whereas co-graft group had less TH and no DAT positive cells.
Conclusions: Our results suggest that the undifferentiated iPSC might induce an immune response against the survival of co-grafted dopaminergic neuron in the striatum of PD rat.