Molecular Mechanisms Responsible for Anti-inflammatory and Immunosuppressive Effects of Mesenchymal Stem Cell-Derived Factors

  • C. Randall Harrell
  • Marina Gazdic Jankovic
  • Crissy Fellabaum
  • Ana Volarevic
  • Valentin Djonov
  • Aleksandar Arsenijevic
  • Vladislav VolarevicEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1084)


Mesenchymal stem cells (MSCs) are self-renewable cells capable for multilineage differentiation and immunomodulation. MSCs are able to differentiate into all cell types of mesodermal origin and, due to their plasticity, may generate cells of neuroectodermal or endodermal origin in vitro. In addition to the enormous differentiation potential, MSCs efficiently modulate innate and adaptive immune response and, accordingly, were used in large number of experimental and clinical trials as new therapeutic agents in regenerative medicine. Although MSC-based therapy was efficient in the treatment of many inflammatory and degenerative diseases, unwanted differentiation of engrafted MSCs represents important safety concern. MSC-based beneficial effects are mostly relied on the effects of MSC-derived immunomodulatory, pro-angiogenic, and trophic factors which attenuate detrimental immune response and inflammation, reduce ischemic injuries, and promote tissue repair and regeneration. Accordingly, MSC-conditioned medium (MSC-CM), which contains MSC-derived factors, has the potential to serve as a cell-free, safe therapeutic agent for the treatment of inflammatory diseases. Herein, we summarized current knowledge regarding identification, isolation, ontogeny, and functional characteristics of MSCs and described molecular mechanisms responsible for MSC-CM-mediated anti-inflammatory and immunosuppressive effects in the therapy of inflammatory lung, liver, and kidney diseases and ischemic brain injury.


Immunosuppression Inflammatory diseases Mesenchymal stem cells Soluble factors Therapy 



Epithelial-to-mesenchymal transition


Amniotic fluid-derived MSCs


Adipose tissue-derived MSCs


Adenosine triphosphate


Brain-derived neurotrophic factor


Bone marrow-derived MSCs


Bone morphogenetic protein


Bronchopulmonary dysplasia


CCAAT/enhancer-binding protein alpha


CC chemokine ligand


Avian myelocytomatosis virus oncogene cellular homolog


Cytotoxic T lymphocytes


Dendritic cells


Extracellular signal-regulated kinases


Embryonic stem cells


Fatty acid-binding protein 4


Fatty acid synthase


First apoptosis signal ligand


Glucose transporter type 4


Granulocyte-macrophage colony-stimulating factor


Human MSCs


Heme oxygenase-1


Indoleamine 2,3-dioxygenase


Interferon beta


Interferon gamma




Insulin-like growth factor 1




Interleukin 1 receptor antagonist


Inducible nitric oxide synthase


Janus kinase


c-Jun N-terminal kinase


Keratinocyte growth factor


Lipoprotein lipase




Mitogen-activated protein kinase


Monocyte colony-stimulating factor


Major histocompatibility complex


Macrophage migration inhibitory factor


MSC-conditioned medium


Mesenchymal stem cells


Murine MSCs


Marginal zone


Neuroepithelial cells


Natural killer


Natural killer T cells


Regulatory NKT cells


Paired box


Prostaglandin E2


Placenta-derived MSCs


Peroxisome proliferator-activated receptor-gamma


Runt-related transcription factor 2


Stem cell factor


Sex-determining region Y-box 9


Stage-specific embryonic antigen


Signal transducer and activator of transcription


Transforming growth factor-beta


Tissue inhibitor of metalloproteinase-1


Toll-like receptor


Tumor necrosis factor alpha


Tumor resistance antigen 1–60


TNF-related apoptosis-inducing ligand


T regulatory cells


TNF-α-stimulated gene/protein 6


Umbilical cord-derived MSCs


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • C. Randall Harrell
    • 1
  • Marina Gazdic Jankovic
    • 2
  • Crissy Fellabaum
    • 1
  • Ana Volarevic
    • 3
  • Valentin Djonov
    • 4
  • Aleksandar Arsenijevic
    • 5
  • Vladislav Volarevic
    • 5
    Email author
  1. 1.Regenerative Processing Plant-RPP, LLCPalm HarborUSA
  2. 2.Department of GeneticsFaculty of Medical Sciences University of KragujevacKragujevacSerbia
  3. 3.Department of PsychologyFaculty of Medical Sciences University of KragujevacKragujevacSerbia
  4. 4.Institute of Anatomy University of BernBernSwitzerland
  5. 5.Department of Microbiology and Immunology, Center for Molecular Medicine and Stem Cell ResearchFaculty of Medical Sciences University of KragujevacKragujevacSerbia

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