Ciervo, Y., Gatto, N., Allen, C. et al. (4 more authors) (2021) Adipose-derived stem cells protect motor neurons and reduce glial activation in both in vitro and in vivo models of ALS. Molecular Therapy — Methods & Clinical Development, 21. pp. 413-433. ISSN 2329-0501
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative condition for which new therapeutic options are urgently needed. We injected GFP+ adipose-derived stem cells (EGFP-ADSCs) directly into the cerebrospinal fluid (CSF) of transgenic SOD1G93A mice, a well-characterized model of familial ALS. Despite short-term survival of the injected cells and limited engraftment efficiency, EGFP-ADSCs improved motor function and delayed disease onset by promoting motor neuron (MN) survival and reducing glial activation. We then tested the in vitro neuroprotective potential of mouse ADSCs in astrocyte/MN co-cultures where ALS astrocytes show neurotoxicity. ADSCs were able to rescue MN death caused by ALS astrocytes derived from symptomatic SOD1G93A mice. Further, ADSCs were found to reduce the inflammatory signature of ALS astrocytes by inhibiting the release of pro-inflammatory mediators and inducing the secretion of neuroprotective factors. Finally, mouse ADSCs were able to protect MNs from the neurotoxicity mediated by human induced astrocytes (iAstrocytes) derived from patients with either sporadic or familial ALS, thus for the first time showing the potential therapeutic translation of ADSCs across the spectrum of human ALS. These data in two translational models of ALS show that, through paracrine mechanisms, ADSCs support MN survival and modulate the toxic microenvironment that contributes to neurodegeneration in ALS.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
Keywords: | amyotrophic lateral sclerosis; neurodegeneration; adipose-derived stem cells; cell therapy |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 16 Apr 2021 08:28 |
Last Modified: | 16 Apr 2021 08:28 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.omtm.2021.03.017 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:173126 |