Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jan 26, 2021; 13(1): 30-48
Published online Jan 26, 2021. doi: 10.4252/wjsc.v13.i1.30
Adipose-derived stem cells: Pathophysiologic implications vs therapeutic potential in systemic sclerosis
Irene Rosa, Eloisa Romano, Bianca Saveria Fioretto, Marco Matucci-Cerinic, Mirko Manetti
Irene Rosa, Mirko Manetti, Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence 50134, Italy
Eloisa Romano, Bianca Saveria Fioretto, Marco Matucci-Cerinic, Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence 50134, Italy
Author contributions: Rosa I and Romano E contributed equally to this work; Rosa I and Romano E wrote the paper; Fioretto BS prepared the figures and tables; Matucci-Cerinic M edited the paper; Manetti M coordinated the writing of the paper and edited the paper; all authors have read and approve the final manuscript.
Conflict-of-interest statement: Authors of this manuscript have no conflicts of interest to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Mirko Manetti, PhD, Assistant Professor, Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Largo Brambilla 3, Florence 50134, Italy.
Received: July 8, 2020
Peer-review started: July 8, 2020
First decision: December 1, 2020
Revised: December 4, 2020
Accepted: December 11, 2020
Article in press: December 11, 2020
Published online: January 26, 2021

Adipose-derived stem cells (ADSCs) residing in the stromal vascular fraction (SVF) of white adipose tissue are recently emerging as an alternative tool for stem cell-based therapy in systemic sclerosis (SSc), a complex connective tissue disorder affecting the skin and internal organs with fibrotic and vascular lesions. Several preclinical and clinical studies have reported promising therapeutic effects of fat grafting and autologous SVF/ADSC-based local treatment for facial and hand cutaneous manifestations of SSc patients. However, currently available data indicate that ADSCs may represent a double-edged sword in SSc, as they may exhibit a pro-fibrotic and anti-adipogenic phenotype, possibly behaving as an additional pathogenic source of pro-fibrotic myofibroblasts through the adipocyte-to-myofibroblast transition process. Thus, in the perspective of a larger employ of SSc-ADSCs for further therapeutic applications, it is important to definitely unravel whether these cells present a comparable phenotype and similar immunosuppressive, anti-inflammatory, anti-fibrotic and pro-angiogenic properties in respect to healthy ADSCs. In light of the dual role that ADSCs seem to play in SSc, this review will provide a summary of the most recent insights into the preclinical and clinical studies employing SVF and ADSCs for the treatment of the disease and, at the same time, will focus on the main findings highlighting the possible involvement of these stem cells in SSc-related fibrosis pathogenesis.

Keywords: Systemic sclerosis, Adipose-derived stromal vascular fraction, Adipose-derived stem cells, Therapeutic approaches, Pathogenesis, Adipocyte-to-myofibroblast transition

Core Tip: Adipose-derived stem cells (ADSCs) represent a promising cell source for cell-based therapy in the treatment of systemic sclerosis (SSc), but at the same time, they may be involved in the disease pathogenesis. In this review, the current status of fat grafting and autologous stromal vascular fraction/ADSC-based therapeutic applications as well as SSc-ADSC functional characterization and possible implication in disease-related fibrosis are discussed.