VEGF-expressing human umbilical cord mesenchymal stem cells, an improved therapy strategy for Parkinson’s disease

Abstract

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.

Transplantation of umbilical cord–derived mesenchymal stem cells as a novel strategy to protect the central nervous system: technical aspects, preclinical studies, and clinical perspectives

“…Several reports have demonstrated neuroprotection after experimental hUC-MSC xenotransplantation with or without immunosuppressive treatment, and there is no consensus as to the need for immunosuppression for optimal neuroprotection. Some studies have shown the survival of numerous transplanted cells for periods as long as 4 mo, even though no immunosuppression was used (6,59,97). Contrarily, in similar animal models, few transplanted cells could be identified a few weeks after transplantation in immunosuppressed animals (98).…”

“…Xiong et al engineered hUC-MSCs to make them express GFP and vascular endothelial growth factor. They injected these cells into the rotenone-lesioned striatum of hemiparkinsonian rats, and observed an improvement in apomorphine-induced rotational behavior (97). It should be noted that despite the absence of immunosuppression, no immunological rejection was observed and many transplanted cells survived up to 12 wk after transplantation.…”

Wharton's Jelly Stem Cells as Agents for Cancer Therapy

“…Both human and rat UCMSC also possess a strong tropism to various tumor tissues [32,33] and other inflammatory lesions [17,34,35]. Both human and rat UCMSC were specifically localized in the periphery of the tumor tissues when they were transplanted ( Fig.…”

“…For example, Yang et al have shown that transplantation of human UCMSC into the lesion site of a spinal cord injury is beneficial to wound healing in rats [16]. Parkinson`s disease is a potential target for the UCMSC therapy since transplanted UCMSC can be differentiated into dopaminergic neuron-like cells [17]. In addition, Chao et al, have reported that human UCMSC can be differentiated into mature islet-like cell clusters, and they possess an insulin-producing ability and significantly alleviated diabetic conditions in rats [18].…”

Controlled Release Strategy Based on Biodegradable Microspheres for Neurodegenerative Disease Therapy

“…Based on the structure and function, neurotrophic factors (NTFs) are divided into several families: (1) nerve growth factor (NGF)-superfamily, including nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin -4/5 (NT-4/5) and neurotrophin-6 (NT-6); (2) glial cell line-derived neurotrophic factor (GDNF) family, including glial cell line derived neurotrophic factor (GDNF), neurturin (NTN) and persephin (PSP); (3) neurokine superfamily, including ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), interleukin (IL) and cardiotrophin (CT); (4) non-neuronal growth factor-superfamily, including some members of fibroblast growth factor superfamily, epidermal growth factor (EGF) [10], insulin-like growth factor (IGF) [11,14], bone morphogenetic protein (BMP) [2,8,12]. Furthermore, other growth factors also have neurotrophic function, such as vascular endothelial growth factor (VEGF) and erythropoietin (EPO) [34,35]. Most of these neurotrophic factors are protein or glycoprotein and are suitable to prepare sustained release microspheres [22,31,[36][37][38][39].…”