Mesenchymal Stem-Cell-Derived Exosomes and MicroRNAs: Advancing Cell-Free Therapy in Systemic Sclerosis

Mesenchymal stem cell (MSC) transplantation has emerged as a potential therapeutic strategy for systemic sclerosis (SSc), a rare autoimmune disease characterized by inflammation, fibrosis, and vasculopathy. Recent evidence suggests that the therapeutic benefits of MSCs do not depend directly on thei...

Full description

Saved in:
Bibliographic Details
Main Authors: Cristiano Barbetta, Francesco Bonomi, Gemma Lepri, Daniel E. Furst, Silvia Bellando Randone, Serena Guiducci
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/14/13/1018
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849429140411777024
author Cristiano Barbetta
Francesco Bonomi
Gemma Lepri
Daniel E. Furst
Silvia Bellando Randone
Serena Guiducci
author_facet Cristiano Barbetta
Francesco Bonomi
Gemma Lepri
Daniel E. Furst
Silvia Bellando Randone
Serena Guiducci
author_sort Cristiano Barbetta
collection DOAJ
description Mesenchymal stem cell (MSC) transplantation has emerged as a potential therapeutic strategy for systemic sclerosis (SSc), a rare autoimmune disease characterized by inflammation, fibrosis, and vasculopathy. Recent evidence suggests that the therapeutic benefits of MSCs do not depend directly on their ability to proliferate but rather on their capacity to release extracellular nanovesicles known as exosomes (MSC-Exos). MSC-Exos are rich in bioactive molecules such as microRNAs, which can modulate gene expression and trigger significant biological responses, playing a central role in modulating immune responses, inhibiting fibrotic pathways and promoting tissue repair and angiogenesis. Preclinical studies have demonstrated that MSC-Exos can attenuate fibrosis, modulate macrophage polarization, suppress autoreactive lymphocyte activity, and even reverse pulmonary arterial hypertension in animal models of SSc. Compared to cell-based therapies, MSC-Exos offer several advantages, including lower immunogenicity and better safety profile. This review provides an overview of the immunomodulatory, antifibrotic, and angiogenic properties of MSC-Exos and explores their potential as novel cell-free therapy for SSc.
format Article
id doaj-art-2f2448dfb69d412280c30ff24a69a8b8
institution Kabale University
issn 2073-4409
language English
publishDate 2025-07-01
publisher MDPI AG
record_format Article
series Cells
spelling doaj-art-2f2448dfb69d412280c30ff24a69a8b82025-08-20T03:28:28ZengMDPI AGCells2073-44092025-07-011413101810.3390/cells14131018Mesenchymal Stem-Cell-Derived Exosomes and MicroRNAs: Advancing Cell-Free Therapy in Systemic SclerosisCristiano Barbetta0Francesco Bonomi1Gemma Lepri2Daniel E. Furst3Silvia Bellando Randone4Serena Guiducci5Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, AOU Careggi, 50121 Florence, ItalyDepartment of Internal Medicine, University Hospital Careggi, 50134 Florence, ItalyDivision of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, AOU Careggi, 50121 Florence, ItalySouthern California Scleroderma and Rheumatology Centre, Los Angeles, CA 90095, USADivision of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, AOU Careggi, 50121 Florence, ItalyDivision of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, AOU Careggi, 50121 Florence, ItalyMesenchymal stem cell (MSC) transplantation has emerged as a potential therapeutic strategy for systemic sclerosis (SSc), a rare autoimmune disease characterized by inflammation, fibrosis, and vasculopathy. Recent evidence suggests that the therapeutic benefits of MSCs do not depend directly on their ability to proliferate but rather on their capacity to release extracellular nanovesicles known as exosomes (MSC-Exos). MSC-Exos are rich in bioactive molecules such as microRNAs, which can modulate gene expression and trigger significant biological responses, playing a central role in modulating immune responses, inhibiting fibrotic pathways and promoting tissue repair and angiogenesis. Preclinical studies have demonstrated that MSC-Exos can attenuate fibrosis, modulate macrophage polarization, suppress autoreactive lymphocyte activity, and even reverse pulmonary arterial hypertension in animal models of SSc. Compared to cell-based therapies, MSC-Exos offer several advantages, including lower immunogenicity and better safety profile. This review provides an overview of the immunomodulatory, antifibrotic, and angiogenic properties of MSC-Exos and explores their potential as novel cell-free therapy for SSc.https://www.mdpi.com/2073-4409/14/13/1018mesenchymal stem cellsexosomesmicroRNAssystemic sclerosis
spellingShingle Cristiano Barbetta
Francesco Bonomi
Gemma Lepri
Daniel E. Furst
Silvia Bellando Randone
Serena Guiducci
Mesenchymal Stem-Cell-Derived Exosomes and MicroRNAs: Advancing Cell-Free Therapy in Systemic Sclerosis
Cells
mesenchymal stem cells
exosomes
microRNAs
systemic sclerosis
title Mesenchymal Stem-Cell-Derived Exosomes and MicroRNAs: Advancing Cell-Free Therapy in Systemic Sclerosis
title_full Mesenchymal Stem-Cell-Derived Exosomes and MicroRNAs: Advancing Cell-Free Therapy in Systemic Sclerosis
title_fullStr Mesenchymal Stem-Cell-Derived Exosomes and MicroRNAs: Advancing Cell-Free Therapy in Systemic Sclerosis
title_full_unstemmed Mesenchymal Stem-Cell-Derived Exosomes and MicroRNAs: Advancing Cell-Free Therapy in Systemic Sclerosis
title_short Mesenchymal Stem-Cell-Derived Exosomes and MicroRNAs: Advancing Cell-Free Therapy in Systemic Sclerosis
title_sort mesenchymal stem cell derived exosomes and micrornas advancing cell free therapy in systemic sclerosis
topic mesenchymal stem cells
exosomes
microRNAs
systemic sclerosis
url https://www.mdpi.com/2073-4409/14/13/1018
work_keys_str_mv AT cristianobarbetta mesenchymalstemcellderivedexosomesandmicrornasadvancingcellfreetherapyinsystemicsclerosis
AT francescobonomi mesenchymalstemcellderivedexosomesandmicrornasadvancingcellfreetherapyinsystemicsclerosis
AT gemmalepri mesenchymalstemcellderivedexosomesandmicrornasadvancingcellfreetherapyinsystemicsclerosis
AT danielefurst mesenchymalstemcellderivedexosomesandmicrornasadvancingcellfreetherapyinsystemicsclerosis
AT silviabellandorandone mesenchymalstemcellderivedexosomesandmicrornasadvancingcellfreetherapyinsystemicsclerosis
AT serenaguiducci mesenchymalstemcellderivedexosomesandmicrornasadvancingcellfreetherapyinsystemicsclerosis