Stem cell transplantation and/or adenoviral glial cell line-derived neurotrophic factor promote functional recovery in hemiparkinsonian rats

BACKGROUND Parkinson’s disease(PD)is a neurological disorder characterized by the progressive loss of midbrain dopamine(DA)neurons.Bone marrow mesenchymal stem cells(BMSCs)can differentiate into multiple cell types including neurons and glia.Transplantation of BMSCs is regarded as a potential approach for promoting neural regeneration.Glial cell line-derived neurotrophic factor(GDNF)can induce BMSC differentiation into neuron-like cells.This work evaluated the efficacy of nigral grafts of human BMSCs(hMSCs)and/or adenoviral(Ad)GDNF gene transfer in 6-hydroxydopamine(6-OHDA)-lesioned hemiparkinsonian rats.AIM To evaluate the efficacy of nigral grafts of hMSCs and/or Ad-GDNF gene transfer in 6-OHDA-lesioned hemiparkinsonian rats.METHODS We used immortalized hMSCs,which retain their potential for neuronal differentiation.hMSCs,preinduced hMSCs,or Ad-GDNF effectively enhanced neuronal connections in cultured neurons.In vivo,preinduced hMSCs and/or Ad-GDNF were injected into the substantia nigra(SN)after induction of a unilateral 6-OHDA lesion in the nigrostriatal pathway.RESULTS Hemiparkinsonian rats that received preinduced hMSC graft and/or Ad-GDNF showed significant recovery of apomorphine-induced rotational behavior and the number of nigral DA neurons.However,DA levels in the striatum were not restored by these therapeutic treatments.Grafted hMSCs might reconstitute a niche to support tissue repair rather than contribute to the generation of new neurons in the injured SN.CONCLUSION The results suggest that preinduced hMSC grafts exert a regenerative effect and may have the potential to improve clinical outcome.