Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy

Alzheimer’s disease (AD) treatment is constrained due to the inability of peripherally administered therapeutic molecules to cross the blood–brain barrier. Encapsulated cell biodelivery (ECB) devices, a tissue-targeted approach for local drug release, was previously optimized for human mature nerve...

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Autores principales:	Sumonto Mitra, Silvia Turchetto, Winant Van Os, Lars U. Wahlberg, Bengt Linderoth, Homira Behbahani, Maria Eriksdotter
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Alzheimer’s disease (AD) astrocytes amyloid beta (Aβ) encapsulated cell biodelivery (ECB) nerve growth factor (NGF) drug delivery strategy optimization Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e39d600451674b41b865b11435764563
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spelling	oai:doaj.org-article:e39d600451674b41b865b114357645632021-11-25T17:07:43ZAmyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy10.3390/cells101128342073-4409https://doaj.org/article/e39d600451674b41b865b114357645632021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2834https://doaj.org/toc/2073-4409Alzheimer’s disease (AD) treatment is constrained due to the inability of peripherally administered therapeutic molecules to cross the blood–brain barrier. Encapsulated cell biodelivery (ECB) devices, a tissue-targeted approach for local drug release, was previously optimized for human mature nerve growth factor (hmNGF) delivery in AD patients but was found to have reduced hmNGF release over time. To understand the reason behind reduced ECB efficacy, we exposed hmNGF-releasing cells (NGC0211) in vitro to human cerebrospinal fluid (CSF) obtained from Subjective Cognitive Impairment (SCI), Lewy Body Dementia (LBD), and AD patients. Subsequently, we exposed NGC0211 cells directly to AD-related factors like amyloid-β peptides (Aβ<sub>40/42</sub>) or activated astrocyte-conditioned medium (Aβ<sub>40/42</sub>/IL-1β/TNFα-treated) and evaluated biochemical stress markers, cell death indicators, cell proliferation marker (Ki67), and hmNGF release. We found that all patients’ CSF significantly reduced hmNGF release from NGC0211 cells in vitro. Aβ<sub>40/42</sub>, inflammatory molecules, and activated astrocytes significantly affected NGC0211 cell proliferation without altering hmNGF release or other parameters important for essential functions of the NGC0211 cells. Long-term constant cell proliferation within the ECB device is critically important to maintain a steady cell population needed for stable mNGF release. These data show hampered proliferation of NGC0211 cells, which may lead to a decline of the NGC0211 cell population in ECBs, thereby reducing hmNGF release. Our study highlights the need for future studies to strengthen ECB-mediated long-term drug delivery approaches.Sumonto MitraSilvia TurchettoWinant Van OsLars U. WahlbergBengt LinderothHomira BehbahaniMaria EriksdotterMDPI AGarticleAlzheimer’s disease (AD)astrocytesamyloid beta (Aβ)encapsulated cell biodelivery (ECB)nerve growth factor (NGF)drug delivery strategy optimizationBiology (General)QH301-705.5ENCells, Vol 10, Iss 2834, p 2834 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease (AD) astrocytes amyloid beta (Aβ) encapsulated cell biodelivery (ECB) nerve growth factor (NGF) drug delivery strategy optimization Biology (General) QH301-705.5
spellingShingle	Alzheimer’s disease (AD) astrocytes amyloid beta (Aβ) encapsulated cell biodelivery (ECB) nerve growth factor (NGF) drug delivery strategy optimization Biology (General) QH301-705.5 Sumonto Mitra Silvia Turchetto Winant Van Os Lars U. Wahlberg Bengt Linderoth Homira Behbahani Maria Eriksdotter Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy
description	Alzheimer’s disease (AD) treatment is constrained due to the inability of peripherally administered therapeutic molecules to cross the blood–brain barrier. Encapsulated cell biodelivery (ECB) devices, a tissue-targeted approach for local drug release, was previously optimized for human mature nerve growth factor (hmNGF) delivery in AD patients but was found to have reduced hmNGF release over time. To understand the reason behind reduced ECB efficacy, we exposed hmNGF-releasing cells (NGC0211) in vitro to human cerebrospinal fluid (CSF) obtained from Subjective Cognitive Impairment (SCI), Lewy Body Dementia (LBD), and AD patients. Subsequently, we exposed NGC0211 cells directly to AD-related factors like amyloid-β peptides (Aβ<sub>40/42</sub>) or activated astrocyte-conditioned medium (Aβ<sub>40/42</sub>/IL-1β/TNFα-treated) and evaluated biochemical stress markers, cell death indicators, cell proliferation marker (Ki67), and hmNGF release. We found that all patients’ CSF significantly reduced hmNGF release from NGC0211 cells in vitro. Aβ<sub>40/42</sub>, inflammatory molecules, and activated astrocytes significantly affected NGC0211 cell proliferation without altering hmNGF release or other parameters important for essential functions of the NGC0211 cells. Long-term constant cell proliferation within the ECB device is critically important to maintain a steady cell population needed for stable mNGF release. These data show hampered proliferation of NGC0211 cells, which may lead to a decline of the NGC0211 cell population in ECBs, thereby reducing hmNGF release. Our study highlights the need for future studies to strengthen ECB-mediated long-term drug delivery approaches.
format	article
author	Sumonto Mitra Silvia Turchetto Winant Van Os Lars U. Wahlberg Bengt Linderoth Homira Behbahani Maria Eriksdotter
author_facet	Sumonto Mitra Silvia Turchetto Winant Van Os Lars U. Wahlberg Bengt Linderoth Homira Behbahani Maria Eriksdotter
author_sort	Sumonto Mitra
title	Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy
title_short	Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy
title_full	Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy
title_fullStr	Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy
title_full_unstemmed	Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy
title_sort	amyloid-beta peptides and activated astroglia impairs proliferation of nerve growth factor releasing cells in vitro: implication for encapsulated cell biodelivery-mediated ad therapy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e39d600451674b41b865b11435764563
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Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy

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