ArticlePloS one2013
Regulated expression of lentivirus-mediated GDNF in human bone marrow-derived mesenchymal stem cells and its neuroprotection on dopaminergic cells in vitro.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 29 citations in OpenAlex.
- Genetically Modified MSCs for Targeted Regeneration: Balancing Efficacy, Biosafety, and GMP Standardization.Cells · 2026Review
- The Use of Neurotrophic Factors as a Promising Strategy for the Treatment of Neurodegenerative Diseases (Review).Bulletin of experimental biology and medicine · 2024Review
- Article
- The Antitumor Effect of Gene-Engineered Exosomes in the Treatment of Brain Metastasis of Breast Cancer.Frontiers in oncology · 2020Article
- Glial cell induced neural differentiation of bone marrow stromal cells.Open medicine (Warsaw, Poland) · 2020Article
- Bone marrow mesenchymal stem cells combined with Sox2 increase the functional recovery in rat with traumatic brain injury.Chinese neurosurgical journal · 2019Article
- Prostaglandin EP2 Receptors Mediate Mesenchymal Stromal Cell-Neuroprotective Effects on Dopaminergic Neurons.Molecular neurobiology · 2018Article
- Dual modulation on glial cells by tetrahydroxystilbene glucoside protects against dopamine neuronal loss.Journal of neuroinflammation · 2018Article
- Lent-On-Plus Lentiviral vectors for conditional expression in human stem cells.Scientific reports · 2016Article
- Tightly regulated 'all-in-one' lentiviral vectors for protection of human hematopoietic cells from anticancer chemotherapy.Gene therapy · 2015Article
- Structural characterization of heparin-induced glyceraldehyde-3-phosphate dehydrogenase protofibrils preventing α-synuclein oligomeric species toxicity.The Journal of biological chemistry · 2014Article
- Transport of glial cell line-derived neurotrophic factor into liposomes across the blood-brain barrier: in vitro and in vivo studies.International journal of molecular sciences · 2014Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene regulation remains one of the major challenges for gene therapy in clinical trials. In the present study, we first generated a binary tetracycline-on (Tet-On) system based on two lentivirus vectors, one expressing both human glial cell line-derived neurotrophic factor (hGDNF) and humanized recombinant green fluorescent protein (hrGFP) genes under second-generation tetracycline response element (TRE), and the other expressing the advanced reverse tetracycline-controlled transactivator--rtTA2S-M2 under a human minimal cytomegalovirus immediate early (CMV-IE) promoter. This system allows simultaneous expression of hGDNF and hrGFP genes in the presence of doxycycline (Dox). Human bone marrow-derived mesenchymal stem cells (hMSCs) were transduced with the binary Tet-On lentivirus vectors and characterized in vitro in the presence (On) or absence (Off) of Dox. The expression of hGDNF and hrGFP transgenes in transduced hMSCs was tightly regulated as determined by flow cytometry (FCM), GDNF enzyme-linked immunosorbent assay (ELISA) and quantitative real time-polymerase chain reaction (qRT-PCR). There was a dose-dependent regulation for hrGFP transgene expression. The levels of hGDNF protein in culture medium were correlated with the mean fluorescence intensity (MFI) units of hrGFP. The levels of transgene background expression were very low in the absence of Dox. The treatment of the conditioned medium from cultures of transduced hMSCs in the presence of Dox protected SH-SY5Y cells against 6-hydroxydopamine (6-OHDA) toxicity as determined by cell viability using 3, [4,5-dimethylthiazol-2-yl]-diphenyltetrazolium bromide (MTT) assay. The treatment of the conditioned medium was also found to improve the survival of dopaminergic (DA) neurons of ventral mesencephalic (VM) tissue in serum-free culture conditions as assessed by cell body area, the number of neurites and dendrite branching points, and proportion of tyrosine hydroxylase (TH)-immunoreactive (IR) cells. Our inducible lentivirus-mediated hGDNF gene delivery system may provide useful tools for basic research on gene therapy for chronic neurological disorders such as Parkinson's disease (PD).
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