Microglia Impairs Proliferation and Induces Senescence In-Vitro in NGF Releasing Cells Used in Encapsulated Cell Biodelivery for Alzheimer's Disease Therapy.
Alzheimer’s disease (AD)
amyloid beta (Aβ)
drug delivery
encapsulated cell biodelivery (ECB)
inflammation
microglia
nerve growth factor (NGF)
senescence
therapy
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
12 Aug 2022
12 Aug 2022
Historique:
received:
11
07
2022
revised:
01
08
2022
accepted:
09
08
2022
entrez:
26
8
2022
pubmed:
27
8
2022
medline:
30
8
2022
Statut:
epublish
Résumé
There is no cure yet available for Alzheimer's disease (AD). We recently optimized encapsulated cell biodelivery (ECB) devices releasing human mature nerve growth factor (hmNGF), termed ECB-NGF, to the basal forebrain of AD patients. The ECB-NGF delivery resulted in increased CSF cholinergic markers, improved glucose metabolism, and positive effects on cognition in AD patients. However, some ECB-NGF implants showed altered hmNGF release post-explantation. To optimize the ECB-NGF platform for future therapeutic purposes, we initiated in-vitro optimization studies by exposing ECB-NGF devices to physiological factors present within the AD brain. We report here that microglia cells can impair hmNGF release from ECB-NGF devices in-vitro, which can be reversed by transferring the devices to fresh culture medium. Further, we exposed the hmNGF secreting human ARPE-19 cell line (NGC0211) to microglia (HMC3) conditioned medium (MCM; untreated or treated with IL-1β/IFNγ/Aβ
Identifiants
pubmed: 36012296
pii: ijms23169011
doi: 10.3390/ijms23169011
pmc: PMC9409429
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
Nerve Growth Factor
9061-61-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Swedish Research Council
ID : 2020-02014
Organisme : Hjärnfonden
ID : FO2020-0228
Organisme : Gun and Bertil Stohne's Foundation
ID : 20200917
Organisme : Gamla Tjänarinnor stiftelse
ID : 2019-00846
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