Prolongation of cardiac allograft survival by syngeneic Hematopoietic stem/progenitor cell transplantation in mice

Li, Jianping; Meng, Xin; Tao, Kaishan; Dou, Kefeng

doi:10.1007/s12325-008-0091-1

Cited by 3 publications

(1 citation statement)

References 21 publications

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“…Mesenchymal stromal cells (MSCs) are considered as “immune privileged cells” due to low expression of MHC-II as well as the absence of costimulatory molecules such as B7-1, B7-2, CD40, and CD40L on the cell surface ( 17 , 18 ). They have been proposed as the promising “live” drugs being able to target the anti-donor immune response and prolong allograft survival in human and rodent studies, which may offer new insights for the prevention of CAV ( 19 – 21 ). Beneficial immunomodulatory effects of MSCs in downregulating the effector function of T cells, B cells, and their paracrine have been shown in experimental transplant models ( 22 – 24 ).…”

Section: Introductionmentioning

confidence: 99%

Melatonin Synergizes With Mesenchymal Stromal Cells Attenuates Chronic Allograft Vasculopathy

et al. 2021

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BackgroundChronic rejection characterized by chronic allograft vasculopathy (CAV) remains a major obstacle to long-term graft survival. Due to multiple complicated mechanisms involved, a novel therapy for CAV remains exploration. Although mesenchymal stromal cells (MSCs) have been ubiquitously applied to various refractory immune-related diseases, rare research makes a thorough inquiry in CAV. Meanwhile, melatonin (MT), a wide spectrum of immunomodulator, plays a non-negligible role in transplantation immunity. Here, we have investigated the synergistic effects of MT in combination with MSCs in attenuation of CAV.MethodsC57BL/6 (B6) mouse recipients receiving BALB/c mouse donor aorta transplantation have been treated with MT and/or adipose-derived MSCs. Graft pathological changes, intragraft immunocyte infiltration, splenic immune cell populations, circulating donor-specific antibodies levels, cytokine profiles were detected on post-operative day 40. The proliferation capacity of CD4+ and CD8+ T cells, populations of Th1, Th17, and Tregs were also assessed in vitro.ResultsGrafts in untreated recipients developed a typical pathological feature of CAV characterized by intimal thickening 40 days after transplantation. Compared to untreated and monotherapy groups, MT in combination with MSCs effectively ameliorated pathological changes of aorta grafts indicated by markedly decreased levels of intimal hyperplasia and the infiltration of CD4+ cells, CD8+ cells, and macrophages, but elevated infiltration of Foxp3+ cells. MT either alone or in combination with MSCs effectively inhibited the proliferation of T cells, decreased populations of Th1 and Th17 cells, but increased the proportion of Tregs in vitro. MT synergized with MSCs displayed much fewer splenic populations of CD4+ and CD8+ T cells, Th1 cells, Th17 cells, CD4+ central memory T cells (Tcm), as well as effector memory T cells (Tem) in aorta transplant recipients. In addition, the percentage of splenic Tregs was substantially increased in the combination therapy group. Furthermore, MT combined with MSCs markedly reduced serum levels of circulating allospecific IgG and IgM, as well as decreased the levels of pro-inflammatory IFN-γ, TNF-α, IL-1β, IL-6, IL-17A, and MCP-1, but increased the level of IL-10 in the recipients.ConclusionsThese data suggest that MT has synergy with MSCs to markedly attenuate CAV and provide a novel therapeutic strategy to improve the long-term allograft acceptance in transplant recipients.

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Section: Introductionmentioning

confidence: 99%

Melatonin Synergizes With Mesenchymal Stromal Cells Attenuates Chronic Allograft Vasculopathy

et al. 2021

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Rapid tolerance induction by hematopoietic progenitor cells in the absence of donor-matched lymphoid cells.

Domen

Sun

et al. 2014

Transplant Immunology

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Induction of tolerance and prolongation of islet allograft survival by syngeneic hematopoietic stem cell transplantation in mice

Yang¹,

Xue²,

Lu³

et al. 2015

Transplant Immunology

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Prolongation of cardiac allograft survival by syngeneic Hematopoietic stem/progenitor cell transplantation in mice

Abstract: We conclude that syngeneic HSCT and HPCT can prolong cardiac allograft survival in mice. These two methods could be promising ways to induce immune tolerance in future organ transplantation.

Cited by 3 publications

References 21 publications

Melatonin Synergizes With Mesenchymal Stromal Cells Attenuates Chronic Allograft Vasculopathy

Melatonin Synergizes With Mesenchymal Stromal Cells Attenuates Chronic Allograft Vasculopathy

Rapid tolerance induction by hematopoietic progenitor cells in the absence of donor-matched lymphoid cells.

Induction of tolerance and prolongation of islet allograft survival by syngeneic hematopoietic stem cell transplantation in mice

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