The umbilical cord provides a rich source of primitive mesenchymal stem cells (human umbilical cord mesenchymal stem cells (HUMSCs)), which have the potential for
transplantation-based treatments of
Parkinson's Disease (PD). Our pervious study indicated that adenovirus-associated virus-mediated intrastriatal delivery of human
vascular endothelial growth factor 165 (
VEGF 165) conferred molecular protection to the dopaminergic system. As both
VEGF and HUMSCs displayed limited neuroprotection, in this study we investigated whether HUMSCs combined with
VEGF expression could offer enhanced neuroprotection. HUMSCs were modified by adenovirus-mediated
VEGF gene transfer, and subsequently transplanted into
rotenone-lesioned striatum of hemiparkinsonian rats. As a result, HUMSCs differentiated into dopaminergic neuron-like cells on the basis of
neuron-specific enolase (NSE) (neuronal marker),
glial fibrillary acidic protein (GFAP) (astrocyte marker),
nestin (neural stem cell marker) and
tyrosine hydroxylase (TH) (dopaminergic marker) expression. Further,
VEGF expression significantly enhanced the dopaminergic differentiation of HUMSCs in vivo. HUMSC
transplantation ameliorated
apomorphine-evoked rotations and reduced the loss of dopaminergic neurons in the lesioned substantia nigra (SNc), which was enhanced significantly by
VEGF expression in HUMSCs. These findings present the suitability of HUMSC as a vector for gene therapy and suggest that stem cell engineering with
VEGF may improve the
transplantation strategy for the treatment of PD.