Development of Good Manufacturing Practice-Compatible Isolation and Culture Methods for Human Olfactory Mucosa-Derived Mesenchymal Stromal Cells
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Published:2024-01-06
Issue:2
Volume:25
Page:743
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Kelly Christopher J.1, Lindsay Susan L.1ORCID, Smith Rebecca Sherrard1, Keh Siew2, Cunningham Kyle T.1, Thümmler Katja1, Maizels Rick M.1, Campbell John D. M.13ORCID, Barnett Susan C.1ORCID
Affiliation:
1. School of Infection and Immunity, 120 University Place, Glasgow G12 8TA, UK 2. New Victoria Hospital, 55 Grange Road, Glasgow G42 9LF, UK 3. Tissues Cells and Advanced Therapeutics, SNBTS, Jack Copland Centre, Edinburgh EH14 4BE, UK
Abstract
Demyelination in the central nervous system (CNS) resulting from injury or disease can cause loss of nerve function and paralysis. Cell therapies intended to promote remyelination of axons are a promising avenue of treatment, with mesenchymal stromal cells (MSCs) a prominent candidate. We have previously demonstrated that MSCs derived from human olfactory mucosa (hOM-MSCs) promote myelination to a greater extent than bone marrow-derived MSCs (hBM-MSCs). However, hOM-MSCs were developed using methods and materials that were not good manufacturing practice (GMP)-compliant. Before considering these cells for clinical use, it is necessary to develop a method for their isolation and expansion that is readily adaptable to a GMP-compliant environment. We demonstrate here that hOM-MSCs can be derived without enzymatic tissue digestion or cell sorting and without culture antibiotics. They grow readily in GMP-compliant media and express typical MSC surface markers. They robustly produce CXCL12 (a key secretory factor in promoting myelination) and are pro-myelinating in in vitro rodent CNS cultures. GMP-compliant hOM-MSCs are comparable in this respect to those grown in non-GMP conditions. However, when assessed in an in vivo model of demyelinating disease (experimental autoimmune encephalitis, EAE), they do not significantly improve disease scores compared with controls, indicating further pre-clinical evaluation is necessary before their advancement to clinical trials.
Funder
Chief Scientist Office Medical Research Council Medical Research Scotland
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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