• Neurosurgery · Sep 2015

    De Novo AVM Growth Secondary to Implantation of Genetically Modified Allogeneic Mesenchymal Stem Cells in the Brain.

    • Makoto Nakamura, Amir Samii, Josef M Lang, Friedrich Götz, Madjid Samii, and Joachim K Krauss.
    • *Department of Neurosurgery, Hannover Medical University, Hannover, Germany; ‡Department of Neurosurgery, International Neuroscience Institute, Hannover, Germany; §Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical University, Hannover, Germany.
    • Neurosurgery. 2015 Sep 16.

    Background And ImportanceLocal biological drug delivery in the brain is an innovative field of medicine that developed rapidly in recent years. Our report illustrates a unique case of de novo development of a cerebral arteriovenous malformation (AVM) after implantation of genetically modified allogeneic mesenchymal stem cells in the brain.Clinical PresentationA 50-year-old man was included in a prospective clinical study (study ID number CM GLP-1/01, 2007-004516-31) investigating a novel neuroprotective approach in stroke patients to prevent perihematomal neuronal damage. In this study, alginate microcapsules containing genetically modified allogeneic mesenchymal stem cells producing the neuroprotective glucagon-like peptide-1 (GLP-1) were implanted. Three years later, the patient presented with aphasia and a focal seizure due to a new left frontal intracerebral hemorrhage. Angiography revealed a de novo left frontal AVM.ConclusionThe development of an AVM within a period of 3 years after implantation of the glucagon-like peptide-1-secreting mesenchymal stem cells suggests a possible relationship. This case exemplifies that further investigations are necessary to assess the safety of genetically modified cell lines for local biological drug delivery in the brain.AbbreviationsALK1, activin-like kinase 1AVM, arteriovenous malformationENG, endoglin; GLP-1, glucagon-like peptide-1GLP-1R, glucagon-like peptide-1 receptorMSC, mesenchymal stem cell.

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