title: De Novo Arteriovenous Malformation Growth Secondary to Implantation of Genetically Modified Allogeneic Mesenchymal Stem Cells in the Brain.
abstract: BACKGROUND
  Local 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.
  
  
  METHODS
  A 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: *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.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamura
authors.forename: Amir
authors.initials: A
authors.lastname: Samii
authors.forename: Josef M
authors.initials: JM
authors.lastname: Lang
authors.forename: Friedrich
authors.initials: F
authors.lastname: Götz
authors.forename: Madjid
authors.initials: M
authors.lastname: Samii
authors.forename: Joachim K
authors.initials: JK
authors.lastname: Krauss
mesh_terms: D001037:Aphasia / Q000209:etiology; D001921:Brain / Q000473:pathology*; D002214:Capsules; D002543:Cerebral Hemorrhage / Q000209:etiology; D015316:Genetic Therapy / Q000009:adverse effects; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000209:etiology* / Q000473:pathology* / Q000601:surgery; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D009474:Neurons / Q000473:pathology; D012640:Seizures / Q000209:etiology; D020521:Stroke / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D002214:Capsules; D052216:Glucagon-Like Peptide 1