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- Title
Development of Good Manufacturing Practice-Compatible Isolation and Culture Methods for Human Olfactory Mucosa-Derived Mesenchymal Stromal Cells.
- Authors
Kelly, Christopher J.; Lindsay, Susan L.; Smith, Rebecca Sherrard; Keh, Siew; Cunningham, Kyle T.; Thümmler, Katja; Maizels, Rick M.; Campbell, John D. M.; Barnett, Susan C.
- 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.
- Subjects
STROMAL cells; CELL culture; CENTRAL nervous system; CURRENT good manufacturing practices; ENDOMETRIUM; OLFACTORY receptors; DEMYELINATION; OLIGODENDROGLIA; MYELINATION
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 2, p743
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25020743