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Title: | The Influence of Lysosomal Stress on Dental Pulp Stem Cell-Derived Schwann Cells | Authors: | LIBBERECHT, Karen DIRKX, Nathalie VANGANSEWINKEL, Tim VANDENDRIES, Wendy LAMBRICHTS, Ivo WOLFS, Esther |
Issue Date: | 2024 | Publisher: | MDPI | Source: | Biomolecules, 14 (4) (Art N° 405) | Abstract: | Background: Dysregulation of the endo-lysosomal-autophagy pathway has been identified as a critical factor in the pathology of various demyelinating neurodegenerative diseases, including peripheral neuropathies. This pathway plays a crucial role in transporting newly synthesized myelin proteins to the plasma membrane in myelinating Schwann cells, making these cells susceptible to lysosome-related dysfunctions. Nevertheless, the specific impact of lysosomal dysfunction in Schwann cells and its contribution to neurodegeneration remain poorly understood. Methods: We aim to mimic lysosomal dysfunction in Schwann cells using chloroquine, a lysosomal dysfunction inducer, and to monitor lysosomal leakiness, Schwann cell viability, and apoptosis over time. Additionally, due to the ethical and experimental issues associated with cell isolation and the culturing of human Schwann cells, we use human dental pulp stem cell-derived Schwann cells (DPSC-SCs) as a model in our study. Results: Chloroquine incubation boosts lysosomal presence as demonstrated by an increased Lysotracker signal. Further in-depth lysosomal analysis demonstrated an increased lysosomal size and permeability as illustrated by a TEM analysis and GAL3-LAMP1 staining. Moreover, an Alamar blue assay and Caspase-3 staining demonstrates a reduced viability and increased apoptosis, respectively. Conclusions: Our data indicate that prolonged lysosomal dysfunction leads to lysosomal permeability, reduced viability, and eventually apoptosis in human DPSC-SCs. | Notes: | Wolfs, E (corresponding author), Hasselt Univ, Biomed Res Inst BIOMED, Fac Med & Life Sci, Lab Funct Imaging & Res Stem Cells, B-3590 Diepenbeek, Belgium. karen.libberecht@uhasselt.be; nathalie.dirkx@uhasselt.be; ivo.lambrichts@uhasselt.be; esther.wolfs@uhasselt.be |
Keywords: | Schwann cells;lysosomal stress;dental pulp stem cells;chloroquine | Document URI: | http://hdl.handle.net/1942/43065 | e-ISSN: | 2218-273X | DOI: | 10.3390/biom14040405 | ISI #: | 001220268300001 | Rights: | 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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