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Adipose-Derived Mesenchymal Stem Cells in Autoimmune Disorders: State of the Art and Perspectives for Systemic Sclerosis

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Abstract

Mesenchymal stromal/stem cells (MSC) are non-hematopoietic multipotent progenitor cells, first described in bone marrow in the middle of last century. Since then, MSC have been the objects of a myriad of publications, progressively increasing our knowledge on their potentialities and bringing high expectancies for their regenerative properties. During the same period, numerous tissues, such as adipose tissue, placenta, or umbilical cord, have been used as alternative sources of MSC in comparison with bone marrow. In particular, considering the accessibility and ease to harvest fat tissue, adipose-derived MSC have gained interest above bone marrow-derived MSC. More recently, the discovery of MSC immunomodulatory properties made MSC-based therapy progressively slip from the field of regenerative medicine to the one of autoimmunity. Indeed, in this group of disorders caused by aberrant activation of the immune system resulting in loss of self-tolerance and auto-reactivity, conventional immunosuppressant may be harmful. One advantage of MSC-based therapy would lie in their immune plasticity, resulting in space and time-limited immunosuppression. More specifically, among autoimmune disorders, systemic sclerosis appears as a peculiar multifaceted disease, in which autoimmune phenomena coexist with vascular abnormalities and multi-visceral fibrosis. Considering the pleiotropic effects of MSC, displaying immunomodulatory, angiogenic and antifibrotic capabilities, MSC-based therapy could counteract the three main pathogenic axes of systemic sclerosis and might thus represent a complete breakthrough in this intractable disease with unmet medical need. In this article, while reviewing most recent literature on MSC biology, we itemize their current applications in the field of autoimmunity and shed light onto the potential use of adipose-derived MSC as an innovative strategy to cure systemic sclerosis.

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Abbreviations

α-SMA:

Alpha-smooth actin muscle

AID:

Autoimmune disorders

AOPP:

Advanced oxidation protein products

ANCA:

Antineutrophil cytoplasm antibodies

ASC:

Adipose-derived mesenchymal stem cells

AT:

Adipose tissue

ATMP:

Advanced-therapy medicinal product

bFGF:

Basic fibroblast growth factor

BILAG:

British Isles Lupus Assessment Group

CD:

Crohn’s disease

CFU-F:

Colony-forming unit fibroblasts

CGH:

Comparative genomic hybridization

CIA:

Collagen-induced arthritis

CNS:

Central nervous system

CXCR4:

Chemokine C-X-C motif receptor 4

DC:

Dendritic cells (mDC: mature, iDC: immature)

EAE:

Experimental acute encephalomyelitis

EC:

Endothelial cells

FDA:

Food and Drug Administration

FISH:

Fluorescence in situ hybridization

GFP:

Green fluorescent protein

GILZ:

Glucocorticoid-induced leucin zipper

GM-CSF:

Granulocyte macrophage stimulating growth factor

GMP:

Good manufacturing practices

GvHD:

Graft vs host disease

HO-1:

Heme oxygenase 1

HOCl:

Hypochlorite

HSCT:

Hematopoietic stem cell transplantation

IA:

Intra-articular

IBD:

Inflammatory bowel diseases

IDO:

Indoleamine 2,3 dioxygenase

IFN:

Interferon

Ig:

Immunoglobulin

IL:

Interleukin

IL1-RA:

Interleukin 1 receptor antagonist

iNOS:

Inducible NO synthase

IP:

Intra-peritoneal

iPSC:

Induced pluripotent stem cells

ISCT:

International Society for Stem Cell Therapy

IT:

Intra-tracheal

IV:

Intravenous

LIF:

Leukemia inhibitory factor

LPS:

Lipopolysaccharide

MHC:

Major histocompatibility complex

MMP:

Metalloprotease

MOG:

Myelin oligodendrocyte glycoprotein

MPC:

Multipotent progenitor cells

mRSS:

Modified Rodnan skin score

MS:

Multiple sclerosis

MSC:

Mesenchymal stromal/stem cells

mMSC:

Murine MSC

hMSC:

Human MSC

BM-MSC:

Bone-marrow derived mesenchymal stem cells

UC-MSC:

Umbilical cord MSC

NK:

Natural killer

OPG:

Osteoprotegerin

PAH:

Pulmonary arterial hypertension

PBMC:

Peripheral blood mononuclear cell

PD-1/PD-L1:

Programmed death-1/ programmed death ligand-1

PGE2:

Prostaglandin E2

PHA:

Phytohemagglutinin

PLP:

Proteolipid proteins

RA:

Rheumatoid arthritis

RANK/RANKL:

Receptor activator of nuclear factor kappa-B/RANK ligand

ROS:

Reactive oxygen species

SCID:

Severe combined immunodeficiency

SCF:

Stem cell factor

SDF-1:

Stromal cell derived factor-1

SLE:

Systemic Lupus Erythematosus

SLEDAI:

SLE disease activity score

SRY:

Sex region of Y chromosome

SSc:

Systemic sclerosis

SVF:

Stromal vascular fraction

TIMP:

Tissue inhibitor of metalloprotease

TNF:

Tumor necrosis factor

TSG-6:

Tumor necrosis factor inducible gene 6

VCAM:

Vascular cell adhesion molecule

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    Authors and Affiliations

    1. Inserm, U 1183, Hôpital Saint-Eloi, F-34295, Montpellier, France

      Alexandre T. J. Maria, Marie Maumus, Christian Jorgensen, Danièle Noël & Philippe Guilpain

    2. Medical School, Montpellier University, F-34967, Montpellier, France

      Alexandre T. J. Maria, Marie Maumus, Alain Le Quellec, Christian Jorgensen, Danièle Noël & Philippe Guilpain

    3. Department of Internal Medicine, Multiorganic Diseases, Saint-Eloi Hospital, F-34295, Montpellier, France

      Alexandre T. J. Maria, Alain Le Quellec & Philippe Guilpain

    4. Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie Hospital, F-34295, Montpellier, France

      Christian Jorgensen & Danièle Noël

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    1. Alexandre T. J. Maria
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    Maria, A.T.J., Maumus, M., Le Quellec, A. et al. Adipose-Derived Mesenchymal Stem Cells in Autoimmune Disorders: State of the Art and Perspectives for Systemic Sclerosis. Clinic Rev Allerg Immunol 52, 234–259 (2017). https://doi.org/10.1007/s12016-016-8552-9

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