Kelly, C. J., Lindsay, S. L. , Smith, R. S., Keh, S., Cunningham, K. T. , Thümmler, K. , Maizels, R. M. , Campbell, J. D.M. and Barnett, S. C. (2024) Development of good manufacturing practice-compatible isolation and culture methods for human olfactory mucosa-derived mesenchymal stromal cells. International Journal of Molecular Sciences, 25(2), 743. (doi: 10.3390/ijms25020743) (PMID:38255817)
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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.
| Item Type: | Articles |
|---|---|
| Additional Information: | This research was funded by the Chief Scientist Office (CSO) grant number TCS/19/22; MRC (MR/V00381x/1; and Medical Research Scotland; SPRINT-MND PhD. |
| Keywords: | Mesenchymal stromal cells, myelination, good manufacturing practice, cellular therapy, olfactory mucosa-derived. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Muecklisch, Dr Katja and Kelly, Dr Christopher and Barnett, Professor Susan and Campbell, Dr John and Lindsay, Dr Susan and Keh, Miss Siew and Cunningham, Dr Kyle and Maizels, Professor Rick and Smith, Miss Rebecca |
| Creator Roles: | Kelly, C.Methodology, Formal analysis, Writing – original draft Lindsay, S.Methodology, Formal analysis, Writing – review and editing Smith, R.Methodology, Formal analysis, Writing – review and editing Cunningham, K.Methodology Muecklisch, K.Resources Maizels, R.Methodology Campbell, J.Conceptualization, Writing – review and editing, Funding acquisition Barnett, S.Conceptualization, Writing – review and editing, Funding acquisition |
| Authors: | Kelly, C. J., Lindsay, S. L., Smith, R. S., Keh, S., Cunningham, K. T., Thümmler, K., Maizels, R. M., Campbell, J. D.M., and Barnett, S. C. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| Journal Name: | International Journal of Molecular Sciences |
| Publisher: | MDPI |
| ISSN: | 1661-6596 |
| ISSN (Online): | 1422-0067 |
| Published Online: | 06 January 2024 |
| Copyright Holders: | Copyright © 2024 The Authors |
| First Published: | First published in International Journal of Molecular Sciences 25(2):743 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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