Clinical-Grade Mesenchymal Stromal Cells Produced Under Various Good Manufacturing Practice Processes Differ in Their Immunomodulatory Properties: Standardization of Immune Quality Controls
- 15 June 2013
- journal article
- research article
- Published by Mary Ann Liebert Inc in Stem Cells and Development
- Vol. 22 (12), 1789-1801
- https://doi.org/10.1089/scd.2012.0594
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.Keywords
This publication has 62 references indexed in Scilit:
- Human multipotent mesenchymal stromal cells use galectin-1 to inhibit immune effector cellsBlood, 2010
- Anti-inflammatory protein TSG-6 reduces inflammatory damage to the cornea following chemical and mechanical injuryProceedings of the National Academy of Sciences of the United States of America, 2010
- Enhanced Indoleamine 2,3‐Dioxygenase Activity in Patients with Severe Sepsis and Septic ShockThe Journal of Infectious Diseases, 2010
- Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformationBlood, 2010
- CD40L induces inflammation and adipogenesis in adipose cells – a potential link between metabolic and cardiovascular diseaseThrombosis and Haemostasis, 2010
- Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell propertiesBlood, 2009
- Adipose tissue-derived mesenchymal stem cells are more potent suppressors of dendritic cells differentiation compared to bone marrow-derived mesenchymal stem cellsImmunology Letters, 2009
- Adipose-Derived Mesenchymal Stem Cells Ameliorate Chronic Experimental Autoimmune EncephalomyelitisThe International Journal of Cell Cloning, 2009
- Intravenous hMSCs Improve Myocardial Infarction in Mice because Cells Embolized in Lung Are Activated to Secrete the Anti-inflammatory Protein TSG-6Cell Stem Cell, 2009
- Species Variation in the Mechanisms of Mesenchymal Stem Cell-Mediated ImmunosuppressionThe International Journal of Cell Cloning, 2009