The Exposure to Osteoarthritic Synovial Fluid Enhances the Immunomodulatory Profile of Adipose Mesenchymal Stem Cell Secretome

Objective. Several clinical studies have proposed the infusion of adipose mesenchymal stem cells (AMSCs) as an alternative therapy for joint diseases with inflammatory components, such as osteoarthritis. Indeed, AMSCs are able to stimulate tissue repair through a paracrine activity and the interacti...

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Main Authors: Adriana Cifù, Rossana Domenis, Massimo Pozzi-Mucelli, Paolo Di Benedetto, Araldo Causero, Massimo Moretti, Marta Stevanato, Cinzia Pistis, Pier Camillo Parodi, Martina Fabris, Francesco Curcio
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2020/4058760
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author Adriana Cifù
Rossana Domenis
Massimo Pozzi-Mucelli
Paolo Di Benedetto
Araldo Causero
Massimo Moretti
Marta Stevanato
Cinzia Pistis
Pier Camillo Parodi
Martina Fabris
Francesco Curcio
author_facet Adriana Cifù
Rossana Domenis
Massimo Pozzi-Mucelli
Paolo Di Benedetto
Araldo Causero
Massimo Moretti
Marta Stevanato
Cinzia Pistis
Pier Camillo Parodi
Martina Fabris
Francesco Curcio
author_sort Adriana Cifù
collection DOAJ
description Objective. Several clinical studies have proposed the infusion of adipose mesenchymal stem cells (AMSCs) as an alternative therapy for joint diseases with inflammatory components, such as osteoarthritis. Indeed, AMSCs are able to stimulate tissue repair through a paracrine activity and the interaction with the inflammatory microenvironment seems to have a critical role. Design. To reproduce the inflammatory microenvironment, AMSCs were exposed to osteoarthritic synovial fluid (SF) for 48 h and the effect of their secretome on differentiation of monocytes (M0) into macrophages M1-like and mature dendritic cells (mDCs) was evaluated. Furthermore, the effect of the secretome of AMSCs exposed to SF was evaluated on the T cell population in terms of T cell proliferation and expansion of T regulatory cells (T reg). Results. Our data show that the exposure of AMSCs to SF activates cells and promotes the release of immunosuppressive factors, which induce macrophage polarization of M0 into the M2-like phenotype and inhibit differentiation of monocytes into mature dendritic cells (mDCs). Only the secretome of exposed AMSCs was able to inhibit T cell proliferation and promote T reg expansion. Conclusions. Our results suggest that the microenvironment plays a fundamental role for the development of anti-inflammatory and immunomodulatory properties of AMSCs.
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spelling doaj-art-bbf71e4abaa74d7096dd7d77e0826b852025-02-03T06:05:18ZengWileyStem Cells International1687-966X1687-96782020-01-01202010.1155/2020/40587604058760The Exposure to Osteoarthritic Synovial Fluid Enhances the Immunomodulatory Profile of Adipose Mesenchymal Stem Cell SecretomeAdriana Cifù0Rossana Domenis1Massimo Pozzi-Mucelli2Paolo Di Benedetto3Araldo Causero4Massimo Moretti5Marta Stevanato6Cinzia Pistis7Pier Camillo Parodi8Martina Fabris9Francesco Curcio10Dipartimento di Area Medica, Università degli Studi di Udine, Udine, ItalyDipartimento di Area Medica, Università degli Studi di Udine, Udine, ItalyDipartimento di Ortopedia e Traumatologia, ASUFC, Udine, ItalyDAME Università degli Studi di Udine, Clinica Ortopedica, ASUFC, Udine, ItalyDAME Università degli Studi di Udine, Clinica Ortopedica, ASUFC, Udine, ItalyVivaBioCell S.p.A., Udine, ItalyDipartimento di Area Medica, Università degli Studi di Udine, Udine, ItalyIstituto di Patologia Clinica, ASUFC, Udine, ItalyDAME Università degli Studi di Udine, Clinica di Chirurgia Plastica, ASUFC, Udine, ItalyDipartimento di Area Medica, Università degli Studi di Udine, Udine, ItalyDipartimento di Area Medica, Università degli Studi di Udine, Udine, ItalyObjective. Several clinical studies have proposed the infusion of adipose mesenchymal stem cells (AMSCs) as an alternative therapy for joint diseases with inflammatory components, such as osteoarthritis. Indeed, AMSCs are able to stimulate tissue repair through a paracrine activity and the interaction with the inflammatory microenvironment seems to have a critical role. Design. To reproduce the inflammatory microenvironment, AMSCs were exposed to osteoarthritic synovial fluid (SF) for 48 h and the effect of their secretome on differentiation of monocytes (M0) into macrophages M1-like and mature dendritic cells (mDCs) was evaluated. Furthermore, the effect of the secretome of AMSCs exposed to SF was evaluated on the T cell population in terms of T cell proliferation and expansion of T regulatory cells (T reg). Results. Our data show that the exposure of AMSCs to SF activates cells and promotes the release of immunosuppressive factors, which induce macrophage polarization of M0 into the M2-like phenotype and inhibit differentiation of monocytes into mature dendritic cells (mDCs). Only the secretome of exposed AMSCs was able to inhibit T cell proliferation and promote T reg expansion. Conclusions. Our results suggest that the microenvironment plays a fundamental role for the development of anti-inflammatory and immunomodulatory properties of AMSCs.http://dx.doi.org/10.1155/2020/4058760
spellingShingle Adriana Cifù
Rossana Domenis
Massimo Pozzi-Mucelli
Paolo Di Benedetto
Araldo Causero
Massimo Moretti
Marta Stevanato
Cinzia Pistis
Pier Camillo Parodi
Martina Fabris
Francesco Curcio
The Exposure to Osteoarthritic Synovial Fluid Enhances the Immunomodulatory Profile of Adipose Mesenchymal Stem Cell Secretome
Stem Cells International
title The Exposure to Osteoarthritic Synovial Fluid Enhances the Immunomodulatory Profile of Adipose Mesenchymal Stem Cell Secretome
title_full The Exposure to Osteoarthritic Synovial Fluid Enhances the Immunomodulatory Profile of Adipose Mesenchymal Stem Cell Secretome
title_fullStr The Exposure to Osteoarthritic Synovial Fluid Enhances the Immunomodulatory Profile of Adipose Mesenchymal Stem Cell Secretome
title_full_unstemmed The Exposure to Osteoarthritic Synovial Fluid Enhances the Immunomodulatory Profile of Adipose Mesenchymal Stem Cell Secretome
title_short The Exposure to Osteoarthritic Synovial Fluid Enhances the Immunomodulatory Profile of Adipose Mesenchymal Stem Cell Secretome
title_sort exposure to osteoarthritic synovial fluid enhances the immunomodulatory profile of adipose mesenchymal stem cell secretome
url http://dx.doi.org/10.1155/2020/4058760
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