Assessment of mesenchymal stem/stromal cell-based therapy in K/BxN serum transfer-induced arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and cartilage/bone destruction with systemic comorbidities. Despite advances in understanding the aetiology of RA and novel biologic drugs, a substantial number of individuals with RA remain intolerant or resist...

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Main Authors: Mercedes Lopez-Santalla, Carmen Conde, Angela Rodriguez-Trillo, Marina I. Garin
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.943293/full
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author Mercedes Lopez-Santalla
Mercedes Lopez-Santalla
Mercedes Lopez-Santalla
Carmen Conde
Angela Rodriguez-Trillo
Marina I. Garin
Marina I. Garin
Marina I. Garin
author_facet Mercedes Lopez-Santalla
Mercedes Lopez-Santalla
Mercedes Lopez-Santalla
Carmen Conde
Angela Rodriguez-Trillo
Marina I. Garin
Marina I. Garin
Marina I. Garin
author_sort Mercedes Lopez-Santalla
collection DOAJ
description Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and cartilage/bone destruction with systemic comorbidities. Despite advances in understanding the aetiology of RA and novel biologic drugs, a substantial number of individuals with RA remain intolerant or resistant to these therapies. In this context, mesenchymal stem/stromal cell (MSC)-based therapy has emerged as an innovative therapeutic alternative to address unresolved treatment issues for patients with RA thanks to the immunomodulatory properties of these cells. The majority of preclinical studies in MSC-based therapy have been conducted using the well-known collagen-induced arthritis (CIA) mouse model however due to its low incidence, the mouse strain restriction and the prolonged induction phase of collagen-induced arthritis, alternative experimental models of RA have been developed such as K/BxN serum transfer-induced arthritis (STIA), which mimics many of human RA features. In this study, we evaluate whether the K/BxN STIA model could be used as an alternative model to study the immunomodulatory potential of MSC-based therapy. Unexpectedly, our data suggest that adipose-derived MSC-based therapy is unsuitable for modulating the progression of K/BxN serum-transfer arthritis in mice despite the various experimental parameters tested. Based on the differences in the immune status and monocytic/macrophage balance among the different arthritic models, these results could help to identify the cellular targets of the MSCs and, most importantly to predict the RA patients that will respond positively to MSC-based therapy.
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spelling doaj.art-d95f976ee3054e03a5a21b2a2c97df182022-12-22T04:29:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.943293943293Assessment of mesenchymal stem/stromal cell-based therapy in K/BxN serum transfer-induced arthritisMercedes Lopez-Santalla0Mercedes Lopez-Santalla1Mercedes Lopez-Santalla2Carmen Conde3Angela Rodriguez-Trillo4Marina I. Garin5Marina I. Garin6Marina I. Garin7Division of Hematopoietic Innovative Therapies, Biomedical Innovation Unit, Centro de Investigaciones Energéticas Medioambientales y Tecnológicas (CIEMAT), Madrid, SpainCentre for Biomedical Network Research on Rare Diseases (CIBER-ER) and Advanced Therapy Unit, Madrid, SpainAdvanced Therapy Unit, Health Research Institute- Fundación Jiménez Díaz, University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, SpainLaboratorio de Reumatología Experimental y Observacional, Instituto de Investigación Sanitaria de Santiago (IDIS), Hospital Clínico Universitario de Santiago de Compostela (CHUS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, SpainLaboratorio de Reumatología Experimental y Observacional, Instituto de Investigación Sanitaria de Santiago (IDIS), Hospital Clínico Universitario de Santiago de Compostela (CHUS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, SpainDivision of Hematopoietic Innovative Therapies, Biomedical Innovation Unit, Centro de Investigaciones Energéticas Medioambientales y Tecnológicas (CIEMAT), Madrid, SpainCentre for Biomedical Network Research on Rare Diseases (CIBER-ER) and Advanced Therapy Unit, Madrid, SpainAdvanced Therapy Unit, Health Research Institute- Fundación Jiménez Díaz, University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, SpainRheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and cartilage/bone destruction with systemic comorbidities. Despite advances in understanding the aetiology of RA and novel biologic drugs, a substantial number of individuals with RA remain intolerant or resistant to these therapies. In this context, mesenchymal stem/stromal cell (MSC)-based therapy has emerged as an innovative therapeutic alternative to address unresolved treatment issues for patients with RA thanks to the immunomodulatory properties of these cells. The majority of preclinical studies in MSC-based therapy have been conducted using the well-known collagen-induced arthritis (CIA) mouse model however due to its low incidence, the mouse strain restriction and the prolonged induction phase of collagen-induced arthritis, alternative experimental models of RA have been developed such as K/BxN serum transfer-induced arthritis (STIA), which mimics many of human RA features. In this study, we evaluate whether the K/BxN STIA model could be used as an alternative model to study the immunomodulatory potential of MSC-based therapy. Unexpectedly, our data suggest that adipose-derived MSC-based therapy is unsuitable for modulating the progression of K/BxN serum-transfer arthritis in mice despite the various experimental parameters tested. Based on the differences in the immune status and monocytic/macrophage balance among the different arthritic models, these results could help to identify the cellular targets of the MSCs and, most importantly to predict the RA patients that will respond positively to MSC-based therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.943293/fullMesenchymal stem/stromal cell-based therapyK/BxN serum transfer-induced arthritisJoint inflammationcell therapyImmunomodulation
spellingShingle Mercedes Lopez-Santalla
Mercedes Lopez-Santalla
Mercedes Lopez-Santalla
Carmen Conde
Angela Rodriguez-Trillo
Marina I. Garin
Marina I. Garin
Marina I. Garin
Assessment of mesenchymal stem/stromal cell-based therapy in K/BxN serum transfer-induced arthritis
Frontiers in Immunology
Mesenchymal stem/stromal cell-based therapy
K/BxN serum transfer-induced arthritis
Joint inflammation
cell therapy
Immunomodulation
title Assessment of mesenchymal stem/stromal cell-based therapy in K/BxN serum transfer-induced arthritis
title_full Assessment of mesenchymal stem/stromal cell-based therapy in K/BxN serum transfer-induced arthritis
title_fullStr Assessment of mesenchymal stem/stromal cell-based therapy in K/BxN serum transfer-induced arthritis
title_full_unstemmed Assessment of mesenchymal stem/stromal cell-based therapy in K/BxN serum transfer-induced arthritis
title_short Assessment of mesenchymal stem/stromal cell-based therapy in K/BxN serum transfer-induced arthritis
title_sort assessment of mesenchymal stem stromal cell based therapy in k bxn serum transfer induced arthritis
topic Mesenchymal stem/stromal cell-based therapy
K/BxN serum transfer-induced arthritis
Joint inflammation
cell therapy
Immunomodulation
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.943293/full
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