Journal
STEM CELLS AND DEVELOPMENT
Volume 22, Issue 12, Pages 1789-1801Publisher
MARY ANN LIEBERT INC
DOI: 10.1089/scd.2012.0594
Keywords
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Funding
- 7th Framework Program of the European Commission: CASCADE [FP7-HEALTH-233236]
- 7th Framework Program of the European Commission: REBORNE [FP7-HEALTH-241879]
- European Center for Transplantation Sciences and Immunotherapy (IHU CESTI) [ANR-10-IBHU-0005]
- Agence Nationale de la Recherche (ANR) [ANR-10-IBHU-0005] Funding Source: Agence Nationale de la Recherche (ANR)
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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-gamma-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.
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