Human adipose-derived mesenchymal stem cells reduce inflammatory and T cell responses and induce regulatory T cells in vitro in rheumatoid arthritis

González‐Rey, Elena; González, Manuel A.; Varela, Nieves; O’Valle, Francisco; Hernández‐Cortés, Pedro; Rico, Laura; Büscher, Dirk; Delgado, Mario

doi:10.1136/ard.2008.101881

Cited by 373 publications

(303 citation statements)

References 29 publications

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“…We recently described the immunosuppressive activity of human AD-MSCs in vitro on cells from RA patients (24). In the present study, we investigated the potential therapeutic action of human AD-MSCs in an experimental model of murine arthritis that shares a number of clinical, histologic, and immunologic features with RA.…”

Section: Resultsmentioning

confidence: 95%

“…Human AD-MSCs directly down-regulated the production of mediators of inflammation by activated synovial cells. Moreover, human AD-MSCs have been shown to inhibit the secretion of various inflammatory cytokines by monocytes isolated from RA patients and macrophages from mice with colitis (24,39). Several studies have also shown that BM-MSCs and AD-MSCs of murine origin are able to down-regulate systemic and local inflammatory responses (11,(14)(15)(16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

“…Large amounts of human AD-MSCs can be easily obtained from lipoaspirates from healthy donors and rapidly expanded in vitro to generate a clinically effective dosage, and recent studies have reported that human AD-MSCs share some of the immunomodulatory properties that characterize the BM-MSCs (18,22,23). Importantly, we recently found that human AD-MSCs exert profound suppressive responses on collagen-reactive T cells from RA patients through various ways (24). Here, we report our findings of the therapeutic effect of human AD-MSCs in experimental arthritis and their capacity to restore immune tolerance and to inhibit the inflammatory response in vivo.…”

mentioning

confidence: 90%

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Treatment of experimental arthritis by inducing immune tolerance with human adipose‐derived mesenchymal stem cells

González¹,

González‐Rey²,

Rico³

et al. 2009

Arthritis & Rheumatism

450

363

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Objective. Rheumatoid arthritis (RA) is a chronic autoimmune disease caused by loss of immunologic self tolerance and characterized by chronic joint inflammation. Adult mesenchymal stem cells (MSCs) were recently found to suppress effector T cell responses and to have beneficial effects in various immune disorders. The purpose of this study was to examine a new therapeutic strategy for RA based on the administration of human adipose-derived MSCs (AD-MSCs).Methods. DBA/1 mice with collagen-induced arthritis were treated with human AD-MSCs after disease onset, and clinical scores were determined. Inflammatory response was determined by measuring the levels of different mediators of inflammation in the joints and serum. The Th1-mediated autoreactive response was evaluated by determining the proliferative response and cytokine profile of draining lymph node cells stimulated with the autoantigen. The number of Treg cells and the suppressive capacity on self-reactive Th1 cells were also determined.Results. Systemic infusion of human AD-MSCs significantly reduced the incidence and severity of experimental arthritis. This therapeutic effect was mediated by down-regulating the 2 deleterious disease components: the Th1-driven autoimmune and inflammatory responses. Human AD-MSCs decreased the production of various inflammatory cytokines and chemokines, decreased antigen-specific Th1/Th17 cell expansion, and induced the production of antiinflammatory interleukin-10 in lymph nodes and joints. Human ADMSCs also induced de novo generation of antigenspecific CD4؉CD25؉FoxP3؉ Treg cells with the capacity to suppress self-reactive T effector responses.Conclusion. Human AD-MSCs emerge as key regulators of immune tolerance by inducing the generation/activation of Treg cells and are thus attractive candidates for a cell-based therapy for RA.

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Section: Resultsmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 90%

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Treatment of experimental arthritis by inducing immune tolerance with human adipose‐derived mesenchymal stem cells

González¹,

González‐Rey²,

Rico³

et al. 2009

Arthritis & Rheumatism

450

363

View full text Add to dashboard Cite

show abstract

“…In a 2009 study Gonzalez-Rey et al [44] found that allogeneic ADSCs were able to suppress the antigen-specific response of T cells from patients with RA. Specifically, ADSC inhibited the proliferative response and the production of inflammatory cytokines by collagen-activated CD4 and CD8 T cells.…”

Section: Evidence For Adsc's Immunomodulatory Capacity: Cell Culture mentioning

confidence: 99%

Allogeneic and Xenogeneic Transplantation of Adipose-Derived Stem Cells in Immunocompetent Recipients Without Immunosuppressants

Lin

Lue

2012

Stem Cells and Development

185

152

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“…[1][2][3][4] ASCs are a desirable therapeutic stem cell source as they are readily available, easily separated from liposuction aspirates or adipose tissue and can be propagated as needed in the laboratory. Data suggests that the therapeutic effects of ASCs are mediated in large part by release of paracrine factors that modulate inflammatory and immune responses or that enhance tissue repair.…”

Section: Introductionmentioning

confidence: 99%

Human cytomegalovirus infection of human adipose-derived stromal/stem cells restricts differentiation along the adipogenic lineage

et al. 2015

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Human adipose-derived stromal/stem cells (ASCs) display potential to be used in regenerative stem cell therapies and as treatments for inflammatory and autoimmune disorders. Despite promising use of ASCs as therapeutics, little is known about their susceptibility to infectious agents. In this study, we demonstrate that ASCs are highly susceptible to human cytomegalovirus (HCMV) infection and permissive for replication leading to release of infectious virions. Additionally, many basic ASC functions are inhibited during HCMV infection, such as differentiation and immunomodulatory potential. To our knowledge this is the first study examining potential adverse effects of HCMV infection on ASC biology. Our results suggest, that an active HCMV infection during ASC therapy may result in a poor clinical outcome due to interference by the virus.

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Human adipose-derived mesenchymal stem cells reduce inflammatory and T cell responses and induce regulatory T cells in vitro in rheumatoid arthritis

Abstract: The present work identifies hASCs as key regulators of immune tolerance, with the capacity to suppress T cell and inflammatory responses and to induce the generation/activation of antigen-specific regulatory T cells.

Cited by 373 publications

References 29 publications

Treatment of experimental arthritis by inducing immune tolerance with human adipose‐derived mesenchymal stem cells

Treatment of experimental arthritis by inducing immune tolerance with human adipose‐derived mesenchymal stem cells

Allogeneic and Xenogeneic Transplantation of Adipose-Derived Stem Cells in Immunocompetent Recipients Without Immunosuppressants

Human cytomegalovirus infection of human adipose-derived stromal/stem cells restricts differentiation along the adipogenic lineage

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