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.
Biomarkers
/ metabolism
Bone Marrow Cells
/ cytology
Cell Culture Techniques
/ methods
Cell Differentiation
Cell Proliferation
Cell Shape
Cells, Cultured
Colony-Forming Units Assay
Humans
Immunity
Immunomodulation
Interferon-gamma
/ metabolism
Mesenchymal Stem Cells
/ cytology
Neovascularization, Physiologic
Pancreas
/ cytology
Regenerative Medicine
T-Lymphocytes
/ cytology
Good Manufacturing Practice
T-cell suppression
chemokines
mesenchymal stromal cells
pancreatic islet
xenogeneic-free
Journal
Cytotherapy
ISSN: 1477-2566
Titre abrégé: Cytotherapy
Pays: England
ID NLM: 100895309
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
09
09
2019
revised:
16
07
2020
accepted:
17
07
2020
pubmed:
24
8
2020
medline:
11
2
2021
entrez:
24
8
2020
Statut:
ppublish
Résumé
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). 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. 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. LPI MSCs represent an alternative source of GMP MSCs with functions comparable to BM MSCs.
Sections du résumé
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.
Identifiants
pubmed: 32828673
pii: S1465-3249(20)30797-0
doi: 10.1016/j.jcyt.2020.07.010
pii:
doi:
Substances chimiques
Biomarkers
0
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
762-771Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : ETM/325
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : TCS/17/31
Pays : United Kingdom
Informations de copyright
Copyright © 2020 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.