title: Clinical-grade mesenchymal stromal cells produced under various good manufacturing practice processes differ in their immunomodulatory properties: standardization of immune quality controls.
abstract: 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: SITI Laboratory, Etablissement Français du Sang Bretagne, CHU Rennes, France.
authors: Cedric
authors: C
authors: Menard
authors: Luciano
authors: L
authors: Pacelli
authors: Giulio
authors: G
authors: Bassi
authors: Joelle
authors: J
authors: Dulong
authors: Francesco
authors: F
authors: Bifari
authors: Isabelle
authors: I
authors: Bezier
authors: Jasmina
authors: J
authors: Zanoncello
authors: Mario
authors: M
authors: Ricciardi
authors: Maelle
authors: M
authors: Latour
authors: Philippe
authors: P
authors: Bourin
authors: Hubert
authors: H
authors: Schrezenmeier
authors: Luc
authors: L
authors: Sensebé
authors: Karin
authors: K
authors: Tarte
authors: Mauro
authors: M
authors: Krampera
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001792:Blood Platelets / Q000737:chemistry / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D002417:Cattle; D002457:Cell Extracts / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D009928:Organ Specificity; D011786:Quality Control; D044967:Serum / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D002457:Cell Extracts; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase