Published online Jan 26, 2021. doi: 10.4252/wjsc.v13.i1.78
Peer-review started: July 20, 2020
First decision: October 21, 2020
Revised: November 4, 2020
Accepted: November 12, 2020
Article in press: November 12, 2020
Published online: January 26, 2021
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.
To evaluate the efficacy of nigral grafts of hMSCs and/or Ad-GDNF gene transfer in 6-OHDA-lesioned hemiparkinsonian rats.
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.
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.
The results suggest that preinduced hMSC grafts exert a regenerative effect and may have the potential to improve clinical outcome.
Core Tip: Strategies to stop neurodegeneration in Parkinson’s disease are currently unavailable. In the present study, transplantation of neurally induced mesenchymal stem cells or overexpressing glial cell line-derived neurotrophic factor to the substantia nigra of hemiparkinsonian rats not only exerted a regenerative effect, but promoted functional restoration. This treatment may have the potential to improve clinical outcome.