Clinical-grade mesenchymal stromal cells produced under various good manufacturing practice processes differ in their immunomodulatory properties: standardization of immune quality controls

Stem Cells Dev. 2013 Jun 15;22(12):1789-801. doi: 10.1089/scd.2012.0594. Epub 2013 Feb 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Adipose Tissue / drug effects
  • Adipose Tissue / immunology
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • Blood Platelets / chemistry
  • Blood Platelets / immunology
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology
  • Cattle
  • Cell Extracts / chemistry
  • Cell Extracts / pharmacology
  • Cell Proliferation
  • Coculture Techniques
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Humans
  • Immunomodulation
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / immunology
  • Organ Specificity
  • Quality Control
  • Serum / chemistry
  • Serum / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology


  • Cell Extracts
  • Cytokines
  • Indoleamine-Pyrrole 2,3,-Dioxygenase