Document Detail


Clinical-grade mesenchymal stromal cells produced under various good manufacturing practice processes differ in their immunomodulatory properties: standardization of immune quality controls.
MedLine Citation:
PMID:  23339531     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Clinical-grade mesenchymal stromal cells (MSCs) are usually expanded from bone marrow (BMMSCs) or adipose tissue (ADSCs) using processes mainly differing in the use of fetal calf serum (FCS) or human platelet lysate (PL). We aimed to compare immune modulatory properties of clinical-grade MSCs using a combination of fully standardized in vitro assays. BMMSCs expanded with FCS (BMMSC-FCS) or PL (BMMSC-PL), and ADSC-PL were analyzed in quantitative phenotypic and functional experiments, including their capacity to inhibit the proliferation of T, B, and NK cells. The molecular mechanisms supporting T-cell inhibition were investigated. These parameters were also evaluated after pre-stimulation of MSCs with inflammatory cytokines. BMMSC-FCS, BMMSC-PL, and ADSC-PL displayed significant differences in expression of immunosuppressive and adhesion molecules. Standardized functional assays revealed that resting MSCs inhibited proliferation of T and NK cells, but not B cells. ADSC-PL were the most potent in inhibiting T-cell growth, a property ascribed to interferon-γ-dependent indoleamine 2,3-dioxygenase activity. MSCs did not stimulate allogeneic T cell proliferation but were efficiently lysed by activated NK cells. The systematic use of quantitative and reproducible validation techniques highlights differences in immunological properties of MSCs produced using various clinical-grade processes. ADSC-PL emerge as a promising candidate for future clinical trials.
Authors:
Cedric Menard; Luciano Pacelli; Giulio Bassi; Joelle Dulong; Francesco Bifari; Isabelle Bezier; Jasmina Zanoncello; Mario Ricciardi; Maelle Latour; Philippe Bourin; Hubert Schrezenmeier; Luc Sensebé; Karin Tarte; Mauro Krampera
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-02-25
Journal Detail:
Title:  Stem cells and development     Volume:  22     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-30     Completed Date:  2013-12-17     Revised Date:  2014-04-10    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1789-801     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / cytology*,  drug effects,  immunology
Animals
B-Lymphocytes / cytology,  immunology
Blood Platelets / chemistry,  immunology
Bone Marrow Cells / cytology*,  drug effects,  immunology
Cattle
Cell Extracts / chemistry,  pharmacology
Cell Proliferation
Coculture Techniques
Cytokines / biosynthesis,  immunology
Humans
Immunomodulation
Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology,  metabolism
Killer Cells, Natural / cytology,  immunology
Mesenchymal Stromal Cells / cytology*,  drug effects,  immunology
Organ Specificity
Quality Control
Serum / chemistry,  immunology
T-Lymphocytes / cytology,  immunology
Chemical
Reg. No./Substance:
0/Cell Extracts; 0/Cytokines; 0/Indoleamine-Pyrrole 2,3,-Dioxygenase
Comments/Corrections

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