Pancreas-derived mesenchymal stromal cells share immune response-modulating and angiogenic potential with bone marrow mesenchymal stromal cells and can be grown to therapeutic scale under Good Manufacturing Practice conditions

Thirlwell, K. L. et al. (2020) Pancreas-derived mesenchymal stromal cells share immune response-modulating and angiogenic potential with bone marrow mesenchymal stromal cells and can be grown to therapeutic scale under Good Manufacturing Practice conditions. Cytotherapy, 22(12), pp. 762-771. (doi: 10.1016/j.jcyt.2020.07.010) (PMID:32828673)

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Abstract

Background aims: Mesenchymal stromal cells (MSCs) isolated from various tissues are under investigation as cellular therapeutics in a wide range of diseases. It is appreciated that the basic biological functions of MSCs vary depending on tissue source. However, in-depth comparative analyses between MSCs isolated from different tissue sources under Good Manufacturing Practice (GMP) conditions are lacking. Human clinical-grade low-purity islet (LPI) fractions are generated as a byproduct of islet isolation for transplantation. MSC isolates were derived from LPI fractions with the aim of performing a systematic, standardized comparative analysis of these cells with clinically relevant bone marrow-derived MSCs (BM MSCs). Methods: MSC isolates were derived from LPI fractions and expanded in platelet lysate-supplemented medium or in commercially available xenogeneic-free medium. Doubling rate, phenotype, differentiation potential, gene expression, protein production and immunomodulatory capacity of LPIs were compared with those of BM MSCs. Results: MSCs can be readily derived in vitro from non-transplanted fractions resulting from islet cell processing (i.e., LPI MSCs). LPI MSCs grow stably in serum-free or platelet lysate-supplemented media and demonstrate in vitro self-renewal, as measured by colony-forming unit assay. LPI MSCs express patterns of chemokines and pro-regenerative factors similar to those of BM MSCs and, importantly, are equally able to attract immune cells in vitro and in vivo and suppress T-cell proliferation in vitro. Additionally, LPI MSCs can be expanded to therapeutically relevant doses at low passage under GMP conditions. Conclusions: LPI MSCs represent an alternative source of GMP MSCs with functions comparable to BM MSCs.

Item Type:Articles
Additional Information:This study was supported in part by the Scottish Chief Scientist Office (grant nos. ETM/325 and TCS/17/31 to JC and SF, principal investigators). KLT was in receipt of a Scottish National Blood Transfusion Service-funded PhD studentship awarded to GJG and JDMC. Work in GJG's lab is supported by a Wellcome Investigator Award and an MRC Programme grant. The Edinburgh Islet Isolation Laboratory is supported by the NHS National Services Division.
Keywords:Good Manufacturing Practice, T-cell suppression, chemokines, mesenchymal stromal cells, pancreatic islet, xenogeneic-free.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mcgowan, Dr Neil and Kelly, Dr Christopher and Mountford, Dr Joanne and Campbell, Dr John and THIRLWELL, Kayleigh and Cuesta Gomez, Miss Nerea and Hewit, Dr Kay and Graham, Professor Gerard
Authors: Thirlwell, K. L., Colligan, D., Mountford, J. C., Samuel, K., Bailey, L., Cuesta-Gomez, N., Hewit, K. D., Kelly, C. J., West, C. C., McGowan, N. W.A., Casey, J. J., Graham, G. J., Turner, M. L., Forbes, S., and Campbell, J. D.M.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Cytotherapy
Publisher:Elsevier
ISSN:1465-3249
ISSN (Online):1477-2566
Published Online:20 August 2020
Copyright Holders:Copyright © 2020 International Society for Cell and Gene Therapy
First Published:First published in Cytotherapy 22(12): 762-771
Publisher Policy:Reproduced under a Creative Commons License

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