Adipose Tissue‐Derived Mesenchymal Stem Cells Have In Vivo Immunosuppressive Properties Applicable for the Control of the Graft‐Versus‐Host Disease

Yáñez, Rosa María Pérez; Lamana, María L.; García‐Castro, Javier; Colmenero, Isabel; Ramı́rez, Manuel; Bueren, Juan A.

doi:10.1634/stemcells.2006-0228

Cited by 651 publications

(478 citation statements)

References 35 publications

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“…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). However, the specific molecular mechanisms involved are not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

“…Human and murine AD-MSCs were obtained essentially as described previously (8,18). Animal experimental protocols were approved by the Ethics Committee of the Spanish Council of Scientific Research.…”

Section: Methodsmentioning

confidence: 99%

“…Besides their capacity to differentiate into mesenchymal and nonmesenchymal cell lineages (7,8) and their potential clinical application for the repair of damaged tissues, several recent studies have shown that bone marrow-derived MSCs (BM-MSCs) regulate the immune response, including in vitro inhibition of T cell proliferation, B cell function, and dendritic cell maturation (9)(10)(11)(12)(13). Some researchers have reported the use of BM-MSCs to treat allograft rejection and acute graftversus-host disease as well as to alleviate experimental autoimmune encephalomyelitis, collagen-induced arthritis (CIA), and autoimmune myocarditis (11,(14)(15)(16)(17)(18)(19)(20). However, the specific molecular and cellular mechanisms involved in the immunoregulatory activity of BM-MSCs remain a subject of controversy.…”

mentioning

confidence: 99%

“…Human MSCs obtained from subcutaneous adipose tissue (AD-MSCs) have recently emerged as an attractive alternative source of MSCs for cell therapy (7,8,10,21). 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).…”

mentioning

confidence: 99%

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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

454

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: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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

454

363

View full text Add to dashboard Cite

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“…The level of hepatocyte growth factor expression has been shown to be much higher in placenta-derived mesenchymal stem cells, compared to adult mesenchymal stem cells (Zhu et al 2014). Mesenchymal stem cells can produce a large number of interleukin (IL)-6, IL-7, IL-11, stromal cell-derived factor, leukemia inhibitor factor, stem cell factor, and Flt3 ligand, which are several essential hematopoietic growth factors (Grebnev et al 2015;Chaudhary et al 1992;Tolar et al 2010;Zhang et al 2011;Dazzi et al 2006;Yañez et al 2006;Sorrentino et al 2008). IL-6 can activate the immune and hematopoietic systems (Lazzari et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Multiplacenta derived stem cell/cytokine treatment increases survival time in a mouse model with radiation-induced bone marrow damage

Wei

Yan

et al. 2016

Cytotechnology

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Nuclear Warfare and nuclear leakage can result in a large number of patients with radiationinduced bone marrow damage. Based on the fact that hematopoietic stem cells and hematopoietic growth factors are characterized as a novel strategy for therapy, the aim of this study was to explore a safe and routine stem cell/cytokine therapeutic strategy. Allogeneic multiplacenta derived hematopoietic and mesenchymal stem cells/cytokines were intraperitoneally injected into a moderate dose of total body irradiation-induced mouse bone marrow damage model a single time. Then, the mouse posttransplantation survival time, peripheral blood hemoglobin count, bone marrow architecture, and donor cell engraftment were assessed. Each mouse that received placenta-derived stem cells exhibited positive donor hematopoietic and mesenchymal stem cell engraftment both in the bone marrow and peripheral blood after transplantation. The peripheral blood hemoglobin count and survival time were greater in the group with the combined treatment of multiplacenta-derived stem cells and cytokines, compared with model-only controls (both P \ 0.001). The blood smear mesenchymal/hematopoietic stem cell count was significantly higher in the combined treatment group than in the mice treated only with placenta-derived cells (28.08 ± 5.824 vs. 20.40 ± 5.989, P \ 0.001; 7.74 ± 2.153 vs. 4.23 ± 1.608, P \ 0.001, respectively). However, there was no marked change on the bone marrow pathology of any of the experimental mice after the transplantation. These results indicate that for radiation-induced bone marrow damage treatment,

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Adipose Tissue–Derived Stem Cells and Their Regeneration Potential

Gimble

Rad

Yao

2013

Stem Cells in Craniofacial Development and Regeneration

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Adipose Tissue‐Derived Mesenchymal Stem Cells Have In Vivo Immunosuppressive Properties Applicable for the Control of the Graft‐Versus‐Host Disease

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Cited by 651 publications

References 35 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

Multiplacenta derived stem cell/cytokine treatment increases survival time in a mouse model with radiation-induced bone marrow damage

Adipose Tissue–Derived Stem Cells and Their Regeneration Potential

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