Administration of Donor-Derived Mesenchymal Stem Cells Can Prolong the Survival of Rat Cardiac Allograft

Zhou, Heping; Yi, Dan; Yu, Shiqiang; Sun, Guocheng; Cui, Qin; Zhu, Hanzhao; Liu, J.C.; Zhang, J.Z.; Wu, T.J.

doi:10.1016/j.transproceed.2006.10.002

Cited by 112 publications

(80 citation statements)

References 26 publications

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“…Bone marrow stromal cells (BMSCs) have recently been shown to suppress harmful immune responses in patients with acute graftversus-host disease (4,5) and in several animal models of allogeneic rejection (6)(7)(8), a variety of autoimmune diseases (9)(10)(11), and lung injury (12)(13)(14)(15). The authors of many of these studies concluded that BMSC-driven immunosuppression results from a shift in Th1/Th2 balance (8,16,17).…”

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confidence: 99%

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Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma

Nemeth

Keane‐Myers

Brown

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

389

350

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Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC-driven immunomodulation is mediated by the suppression of proinflammatory Th1 responses while rebalancing the Th1/Th2 ratio toward Th2. In this study, using a ragweed induced mouse asthma model, we studied if BMSCs could be beneficial in an allergic, Th2-dominant environment. When BMSCs were injected i.v. at the time of the antigen challenge, they protected the animals from the majority of asthma-specific pathological changes, including inhibition of eosinophil infiltration and excess mucus production in the lung, decreased levels of Th2 cytokines (IL-4, IL-5, and IL-13) in bronchial lavage, and lowered serum levels of Th2 immunoglobulins (IgG1 and IgE). To explore the mechanism of the effect we used BMSCs isolated from a variety of knockout mice, performed in vivo blocking of cytokines and studied the effect of asthmatic serum and bronchoalveolar lavage from ragweed challenged animals on the BMSCs in vitro. Our results suggest that IL-4 and/or IL-13 activate the STAT6 pathway in the BMSCs resulting in an increase of their TGF-β production, which seems to mediate the beneficial effect, either alone, or together with regulatory T cells, some of which might be recruited by the BMSCs. These data suggest that, in addition to focusing on graft-versus-host disease and autoimmune diseases, allergic conditions—specifically therapy resistant asthma—might also be a likely target of the recently discovered cellular therapy approach using BMSCs.

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mentioning

confidence: 99%

“…The authors of many of these studies concluded that BMSC-driven immunosuppression results from a shift in Th1/Th2 balance (8,16,17). During BMSC treatment, Th1 responses appear to be decreasing while Th2 responses begin to dominate.…”

mentioning

confidence: 99%

Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma

Nemeth

Keane‐Myers

Brown

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

389

350

View full text Add to dashboard Cite

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“…The immunosuppressive effect and low immunogenicity of mesenchymal stem cells (MSCs) make them ideal candidates for immunosuppressive strategies [3,4]. Adult MSCs have been used widely in the allogeneic heart [5][6][7][8][9][10][11], liver [12], islet [13][14][15][16][17], kidney [18,19], and composite tissue transplants [20,21]. Bone marrow mesenchymal stem cells (BM-MSCs) alone prolong heart allograft survival [8].…”

Section: Introductionmentioning

confidence: 99%

iPSC-MSCs Combined with Low-Dose Rapamycin Induced Islet Allograft Tolerance Through Suppressing Th1 and Enhancing Regulatory T-Cell Differentiation

Cheng

Xiao-cun

et al. 2015

Stem Cells and Development

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Mesenchymal stem cell (MSC) differentiation is dramatically reduced after long-term in vitro culture, which limits their application. MSCs derived from induced pluripotent stem cells (iPSCs-MSCs) represent a novel source of MSCs. In this study, we investigated the therapeutic effect of iPSC-MSCs on diabetic mice. Streptozocin-induced diabetic mice transplanted with 400 islets alone or with 1 · 10 6 iPSC-MSCs were examined following rapamycin injection (0.1 mg/kg/day, i.p., from days 0 to 9) after transplantation. Our results showed that iPSC-MSCs combined with rapamycin significantly prolonged islet allograft survival in the diabetic mice; 50% of recipients exhibited long-term survival ( > 100 days). Histopathological analysis revealed that iPSCMSCs combined with rapamycin preserved the graft effectively, inhibited inflammatory cell infiltration, and resulted in substantial release of insulin. Flow cytometry results showed that the proportion of CD4 + and CD8 + T cells was significantly reduced, and the number of T regulatory cells increased in the spleen and lymph nodes in the iPSC-MSCs combined with the rapamycin group compared with the rapamycin-alone group. Production of the Th1 proinflammatory cytokines interleukin-2 (IL-2) and interferon-g was reduced, and secretion of the anti-inflammatory cytokines IL-10 and transforming growth factor-b was enhanced compared with the rapamycin group, as determined using enzyme-linked immunosorbent assays. Transwell separation significantly weakened the immunosuppressive effects of iPSC-MSCs on the proliferation of Con A-treated splenic T cells, which indicated that the combined treatment exerted immunosuppressive effects through cell-cell contact and regulation of cytokine production. Taken together, these findings highlight the potential application of iPSCMSCs in islet transplantation.

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“…A maioria dos estudos para o tratamento do infarto do miocárdio emprega a utilização de células adultas, como o mioblasto esquelético 6,7 , de células mesenquimais [8][9][10] , e de células mononucleares da medula óssea, obtidas por meio de punção da medula óssea 11 .…”

Section: Introductionunclassified

Padrão de distribuição de células mononucleares de medula óssea em tecido cardíaco sadio por diferentes vias de infusão

Samoto¹,

Branco²,

Ferreira³

et al. 2009

Rev. Bras. Cardiol. Invasiva

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Administration of Donor-Derived Mesenchymal Stem Cells Can Prolong the Survival of Rat Cardiac Allograft

Cited by 112 publications

References 26 publications

Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma

Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma

iPSC-MSCs Combined with Low-Dose Rapamycin Induced Islet Allograft Tolerance Through Suppressing Th1 and Enhancing Regulatory T-Cell Differentiation

Padrão de distribuição de células mononucleares de medula óssea em tecido cardíaco sadio por diferentes vias de infusão

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