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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)

Abstract

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.

Keywords

Immunosuppression Inflammatory diseases Mesenchymal stem cells Soluble factors Therapy 

Abbreviations

(EMT)

Epithelial-to-mesenchymal transition

AF-MSCs

Amniotic fluid-derived MSCs

AT-MSCs

Adipose tissue-derived MSCs

ATP

Adenosine triphosphate

BDNF

Brain-derived neurotrophic factor

BM-MSCs

Bone marrow-derived MSCs

BMP

Bone morphogenetic protein

BPD

Bronchopulmonary dysplasia

C/EBPα

CCAAT/enhancer-binding protein alpha

CCL

CC chemokine ligand

c-MYC

Avian myelocytomatosis virus oncogene cellular homolog

CTLs

Cytotoxic T lymphocytes

DCs

Dendritic cells

ERK

Extracellular signal-regulated kinases

ESCs

Embryonic stem cells

FABP4

Fatty acid-binding protein 4

FAS

Fatty acid synthase

FasL

First apoptosis signal ligand

GLUT4

Glucose transporter type 4

GM-CSF

Granulocyte-macrophage colony-stimulating factor

hMSCs

Human MSCs

HO-1

Heme oxygenase-1

IDO

Indoleamine 2,3-dioxygenase

IFN-β

Interferon beta

IFN-γ

Interferon gamma

Ig

Immunoglobulin

IGF-1

Insulin-like growth factor 1

IL

Interleukin

IL-1Ra

Interleukin 1 receptor antagonist

iNOS

Inducible nitric oxide synthase

JAK

Janus kinase

JNK

c-Jun N-terminal kinase

KGF

Keratinocyte growth factor

LPL

Lipoprotein lipase

LPS

Lipopolysaccharides

MAPK

Mitogen-activated protein kinase

M-CSF

Monocyte colony-stimulating factor

MHC

Major histocompatibility complex

MIF

Macrophage migration inhibitory factor

MSC-CM

MSC-conditioned medium

MSCs

Mesenchymal stem cells

mMSCs

Murine MSCs

MZ

Marginal zone

NECs

Neuroepithelial cells

NK

Natural killer

NKT

Natural killer T cells

NKTregs

Regulatory NKT cells

PAX

Paired box

PGE2

Prostaglandin E2

PL-MSCs

Placenta-derived MSCs

PPAR-γ

Peroxisome proliferator-activated receptor-gamma

RUNX2

Runt-related transcription factor 2

SCF

Stem cell factor

Sox9

Sex-determining region Y-box 9

SSEA

Stage-specific embryonic antigen

STAT

Signal transducer and activator of transcription

TGF-β

Transforming growth factor-beta

TIMP-1

Tissue inhibitor of metalloproteinase-1

TLR

Toll-like receptor

TNF-α

Tumor necrosis factor alpha

TRA-1–60

Tumor resistance antigen 1–60

TRAIL

TNF-related apoptosis-inducing ligand

Tregs

T regulatory cells

TSG-6

TNF-α-stimulated gene/protein 6

UC-MSCs

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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