title: Therapeutic concentrations of glucagon-like peptide-1 in cerebrospinal fluid following cell-based delivery into the cerebral ventricles of cats.
abstract: BACKGROUND
  Neuropeptides may have considerable potential in the treatment of acute and chronic neurological diseases. Encapsulated genetically engineered cells have been suggested as a means for sustained local delivery of such peptides to the brain. In our experiments, we studied human mesenchymal stem cells which were transfected to produce glucagon-like peptide-1 (GLP-1).
  
  
  METHODS
  Cells were packed in a water-permeable mesh bag containing 400 polymeric microcapsules, each containing 3000 cells. The mesh bags were either transplanted into the subdural space, into the brain parenchyma or into the cerebral ventricles of the cat brain. Mesh bags were explanted after two weeks, and cell viability, as well as GLP-1 concentration in the cerebrospinal fluid (CSF), was measured.
  
  
  RESULTS
  Viability of cells did not significantly differ between the three implantation sites. However, CSF concentration of GLP-1 was significantly elevated only after ventricular transplantation with a maximum concentration of 73 pM (binding constant = 70 pM).
  
  
  CONCLUSIONS
  This study showed that ventricular cell-based delivery of soluble factors has the capability to achieve concentrations in the CSF which may become pharmacologically active. Despite the controversy about the pharmacokinetic limitations of ventricular drug delivery, there might be a niche in this for encapsulated cell biodelivery of soluble, highly biologically-effective neuropeptides of low molecular weight like GLP-1.
authors.affiliation: Neurosurgery Foundation, 55 Claverick Str,, Providence, RI 02903, USA. thbrinker@gmail.com.
authors.forename: Silke
authors.initials: S
authors.lastname: Glage
authors.forename: Petra M
authors.initials: PM
authors.lastname: Klinge
authors.forename: Miles C
authors.initials: MC
authors.lastname: Miller
authors.forename: Christine
authors.initials: C
authors.lastname: Wallrapp
authors.forename: Peter
authors.initials: P
authors.lastname: Geigle
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Hedrich
authors.forename: Thomas
authors.initials: T
authors.lastname: Brinker