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Article

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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Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, 141 52 Stockholm, Sweden
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Division of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, 171 64 Stockholm, Sweden
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GIGA-Stem Cells and GIGA-Neurosciences, Interdisciplinary Cluster for Applied Geno-Proteomics (GIGA-R), University of Liège, 4000 Liège, Belgium
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Wiskunde en Natuurwetenschappen, LIC/Chemical Biology, Leiden Institute of Chemistry, 2300 RA Leiden, The Netherlands
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Gloriana Therapeutics, Inc., Warren, Rhode Island, RI 02885, USA
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Department of Clinical Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden
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Karolinska University Laboratories, Karolinska University Hospital, 184 50 Stockholm, Sweden
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Theme Aging, Karolinska University Hospital, 141 86 Huddinge, Sweden
*
Authors to whom correspondence should be addressed.
Academic Editors: Simona Capsoni and Arpad Dobolyi
Cells 2021, 10(11), 2834; https://doi.org/10.3390/cells10112834
Received: 17 August 2021 / Revised: 29 September 2021 / Accepted: 14 October 2021 / Published: 21 October 2021
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 (Aβ40/42) or activated astrocyte-conditioned medium (Aβ40/42/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. Aβ40/42, 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. View Full-Text
Keywords: Alzheimer’s disease (AD); astrocytes; amyloid beta (Aβ); encapsulated cell biodelivery (ECB); nerve growth factor (NGF); drug delivery strategy optimization; inflammation Alzheimer’s disease (AD); astrocytes; amyloid beta (Aβ); encapsulated cell biodelivery (ECB); nerve growth factor (NGF); drug delivery strategy optimization; inflammation
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MDPI and ACS Style

Mitra, S.; Turchetto, S.; Van Os, W.; Wahlberg, L.U.; Linderoth, B.; Behbahani, H.; Eriksdotter, M. Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy. Cells 2021, 10, 2834. https://doi.org/10.3390/cells10112834

AMA Style

Mitra S, Turchetto S, Van Os W, Wahlberg LU, Linderoth B, Behbahani H, Eriksdotter M. Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy. Cells. 2021; 10(11):2834. https://doi.org/10.3390/cells10112834

Chicago/Turabian Style

Mitra, Sumonto, Silvia Turchetto, Winant Van Os, Lars U. Wahlberg, Bengt Linderoth, Homira Behbahani, and Maria Eriksdotter. 2021. "Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy" Cells 10, no. 11: 2834. https://doi.org/10.3390/cells10112834

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