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
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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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