Therapeutic concentrations of glucagon-like peptide-1 in cerebrospinal fluid following cell-based delivery into the cerebral ventricles of cats 英文参考文献.docVIP

Therapeutic concentrations of glucagon-like peptide-1 in cerebrospinal fluid following cell-based delivery into the cerebral ventricles of cats 英文参考文献.doc

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Therapeutic concentrations of glucagon-like peptide-1 in cerebrospinal fluid following cell-based delivery into the cerebral ventricles of cats 英文参考文献

Glageetal.FluidsandBarriersoftheCNS2011,8:18 /content/8/1/18 FLUIDS AND BARRIERS OF THE CNS RESEARCH OpenAccess Therapeuticconcentrationsofglucagon-like peptide-1incerebrospinalfluidfollowingcell- baseddeliveryintothecerebralventriclesofcats SilkeGlage1,PetraMKlinge2,MilesCMiller2,ChristineWallrapp4,PeterGeigle4,HansJHedrich1and ThomasBrinker2,3* Abstract Background:Neuropeptidesmayhaveconsiderablepotentialinthetreatmentofacuteandchronicneurological diseases.Encapsulatedgeneticallyengineeredcellshavebeensuggestedasameansforsustainedlocaldeliveryof suchpeptidestothebrain.Inourexperiments,westudiedhumanmesenchymalstemcellswhichwere transfectedtoproduceglucagon-likepeptide-1(GLP-1). Methods:Cellswerepackedinawater-permeablemeshbagcontaining400polymericmicrocapsules,each containing3000cells.Themeshbagswereeithertransplantedintothesubduralspace,intothebrainparenchyma orintothecerebralventriclesofthecatbrain.Meshbagswereexplantedaftertwoweeks,andcellviability,aswell asGLP-1concentrationinthecerebrospinalfluid(CSF),wasmeasured. Results:Viabilityofcellsdidnotsignificantlydifferbetweenthethreeimplantationsites.However,CSF concentrationofGLP-1wassignificantlyelevatedonlyafterventriculartransplantationwithamaximum concentrationof73pM(bindingconstant=70pM). Conclusions:Thisstudyshowedthatventricularcell-baseddeliveryofsolublefactorshasthecapabilitytoachieve concentrationsintheCSFwhichmaybecomepharmacologicallyactive.Despitethecontroversyaboutthe pharmacokineticlimitationsofventriculardrugdelivery,theremightbeanicheinthisforencapsulatedcell biodeliveryofsoluble,highlybiologically-effectiveneuropeptidesoflowmolecularweightlikeGLP-1. Background autologous cell lines cells can beused, that have been Neurotrophicpeptidesmayhaveconsiderablepotentialin geneticallyengineeredtoproducetheprotein.Toprevent thetreatmentofacuteandchronicneurologicaldiseases. host versus graft reaction, encapsulation ofthose cells However,systemicdeliveryislimitedbysignificant sys- withpermse

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