Abstract
BackgroundNeuropeptides 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).MethodsCells 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.ResultsViability 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).ConclusionsThis 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.
Highlights
Neuropeptides may have considerable potential in the treatment of acute and chronic neurological diseases
Local administration into the central nervous system (CNS) has been proposed [1,2]. This drug delivery route, bypassing the blood brain barrier, has been challenged, because substances are rapidly removed from the brain through physiological cerebrospinal fluid (CSF) outflow pathways [3,4,5]
Increased glucagon-like peptide-1 (GLP-1) concentrations were only found in the CSF, but not in the blood plasma, and only after intra-ventricular implantation both at 7 and 14 days following implantation
Summary
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. Neurotrophic peptides may have considerable potential in the treatment of acute and chronic neurological diseases. Local administration into the central nervous system (CNS) has been proposed [1,2]. This drug delivery route, bypassing the blood brain barrier, has been challenged, because substances are rapidly removed from the brain through physiological cerebrospinal fluid (CSF) outflow pathways [3,4,5]. Ex vivo gene therapy using encapsulated cell biodelivery has been suggested as a way to achieve a more sustained local delivery of proteins into the CNS.
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