Clinical Reviews in Allergy & Immunology

, Volume 52, Issue 2, pp 234–259 | Cite as

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

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

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.

Keywords

Autoimmune disorders Systemic sclerosis Mesenchymal stem cells (MSC) Adipose-derived mesenchymal stem cells (ASC) Cell therapy Fibrosis Autoimmunity 

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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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Alexandre T. J. Maria
    • 1
    • 2
    • 3
  • Marie Maumus
    • 1
    • 2
  • Alain Le Quellec
    • 2
    • 3
  • Christian Jorgensen
    • 1
    • 2
    • 4
  • Danièle Noël
    • 1
    • 2
    • 4
  • Philippe Guilpain
    • 1
    • 2
    • 3
  1. 1.Inserm, U 1183Hôpital Saint-EloiMontpellierFrance
  2. 2.Medical SchoolMontpellier UniversityMontpellierFrance
  3. 3.Department of Internal Medicine, Multiorganic DiseasesSaint-Eloi HospitalMontpellierFrance
  4. 4.Clinical Immunology and Osteoarticular Diseases Therapeutic UnitLapeyronie HospitalMontpellierFrance

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