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

Neurosurgery. 2016 Apr;78(4):E596-600. doi: 10.1227/NEU.0000000000001025.

Abstract

Background and importance: 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.

Clinical presentation: 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.

Conclusion: 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.

Publication types

  • Case Reports

MeSH terms

  • Aphasia / etiology
  • Brain / pathology*
  • Capsules
  • Cerebral Hemorrhage / etiology
  • Genetic Therapy / adverse effects
  • Glucagon-Like Peptide 1 / biosynthesis
  • Glucagon-Like Peptide 1 / genetics
  • Humans
  • Intracranial Arteriovenous Malformations / etiology*
  • Intracranial Arteriovenous Malformations / pathology*
  • Intracranial Arteriovenous Malformations / surgery
  • Male
  • Mesenchymal Stem Cell Transplantation / adverse effects*
  • Middle Aged
  • Neurons / pathology
  • Seizures / etiology
  • Stroke / surgery
  • Treatment Outcome

Substances

  • Capsules
  • Glucagon-Like Peptide 1