ArticleExperimental neurology2007
Lentiviral RNAi-induced downregulation of adenosine kinase in human mesenchymal stem cell grafts: a novel perspective for seizure control.
Article in Experimental neurology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 98 citations in OpenAlex.
- Stem cell-based therapeutics in epilepsy: current advances and future prospects.Stem cells translational medicine · 2026Review
- Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release.Cellular and molecular life sciences : CMLS · 2025Article
- Review
- ATP and adenosine-Two players in the control of seizures and epilepsy development.Progress in neurobiology · 2021Review
- An Analysis of Mechanisms for Cellular Uptake of miRNAs to Enhance Drug Delivery and Efficacy in Cancer Chemoresistance.Non-coding RNA · 2021Review
- Role of Adenosine in Epilepsy and Seizures.Journal of caffeine and adenosine research · 2020Review
- The role of adenosine in epilepsy.Brain research bulletin · 2019Review
- Research progress on adenosine in central nervous system diseases.CNS neuroscience & therapeutics · 2019Review
- Astrocyte adenosine deaminase loss increases motor neuron toxicity in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2019Article
- Genome Editing in Neuroepithelial Stem Cells to Generate Human Neurons with High Adenosine-Releasing Capacity.Stem cells translational medicine · 2018Article
- Stable Knockdown of Adenosine Kinase by Lentiviral Anti-ADK miR-shRNAs in Wharton's Jelly Stem Cells.Cell journal · 2018Article
- Synthetic bioreducible lipid-based nanoparticles for miRNA delivery to mesenchymal stem cells to induce neuronal differentiation.Bioengineering & translational medicine · 2016Article
- Adenosinergic signaling in epilepsy.Neuropharmacology · 2016Review
- Comorbidities in Neurology: Is adenosine the common link?Neuropharmacology · 2015Review
- Defective Self-Renewal and Differentiation of GBA-Deficient Neural Stem Cells Can Be Restored By Macrophage Colony-Stimulating Factor.Molecules and cells · 2015Article
- Mesenchymal stem/stromal cells as a delivery platform in cell and gene therapies.BMC medicine · 2015Review
- A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts.Molecular neurobiology · 2015Review
- Adenosine-associated delivery systems.Journal of drug targeting · 2015Review
- Adenosine kinase, glutamine synthetase and EAAT2 as gene therapy targets for temporal lobe epilepsy.Gene therapy · 2014Article
- The imbalanced expression of adenosine receptors in an epilepsy model corrected using targeted mesenchymal stem cell transplantation.Molecular neurobiology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Cell therapies based on focal delivery of the inhibitory neuromodulator adenosine were previously shown to provide potent seizure suppression in animal models of epilepsy. However, hitherto used therapeutic cells were derived from rodents and thus not suitable for clinical applications. Autologous patient-derived adenosine-releasing cell implants would constitute a major therapeutic advance to avoid both xenotransplantation and immunosuppression. Here we describe a novel approach based on lentiviral RNAi mediated downregulation of adenosine kinase (ADK), the major adenosine-removing enzyme, in human mesenchymal stem cells (hMSCs), which would be compatible with autologous cell grafting in patients. Following lentiviral transduction of hMSCs with anti-ADK miRNA expression cassettes we demonstrate up to 80% downregulation of ADK and a concentration of 8.5 ng adenosine per ml of medium after incubating 10(5) cells for 8 h. hMSCs with a knockdown of ADK or cells expressing a scrambled control sequence were transplanted into hippocampi of mice 1 week prior to the intraamygdaloid injection of kainic acid (KA). While mice with control implants expressing a scrambled miRNA sequence or sham treated control animals were characterized by KA-induced status epilepticus and subsequent CA3 neuronal cell loss, animals with therapeutic ADK knockdown implants displayed a 35% reduction in seizure duration and 65% reduction in CA3 neuronal cell loss, when analyzed 24 h after KA-injection. We conclude that lentiviral expression of anti-ADK miRNA constitutes a versatile tool to generate therapeutically effective adenosine releasing hMSCs, thus representing a model system to generate patient identical autologous adult stem cell grafts.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.