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

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Tissue Engineering and Regenerative Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((ICRRM,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.

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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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Authors and Affiliations

  1. Regenerative Processing Plant-RPP, LLC, Palm Harbor, FL, USA

    C. Randall Harrell & Crissy Fellabaum

  2. Department of Genetics, Faculty of Medical Sciences University of Kragujevac, Kragujevac, Serbia

    Marina Gazdic Jankovic

  3. Department of Psychology, Faculty of Medical Sciences University of Kragujevac, Kragujevac, Serbia

    Ana Volarevic

  4. Institute of Anatomy University of Bern, Bern, Switzerland

    Valentin Djonov

  5. Department of Microbiology and Immunology, Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences University of Kragujevac, Kragujevac, Serbia

    Aleksandar Arsenijevic & Vladislav Volarevic

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    Phuc Van Pham

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Harrell, C.R. et al. (2018). Molecular Mechanisms Responsible for Anti-inflammatory and Immunosuppressive Effects of Mesenchymal Stem Cell-Derived Factors. In: Pham, P. (eds) Tissue Engineering and Regenerative Medicine. Advances in Experimental Medicine and Biology(), vol 1084. Springer, Cham. https://doi.org/10.1007/5584_2018_306

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