主页 > 医学新闻 >
【Diabetes】间充质干细胞：对胰岛移植具有帮助作
Type 1 diabetes is a disorder caused by the autoimmune-mediated destruction of insulin-producing β-cells in the pancreas (1). Many promising intervention trials are currently underway or in development to prevent β-cell loss in patients with recent-onset type 1 diabetes and in individuals at increased risk for type 1 diabetes due to the presence of autoantibodies or elevated genetic risk (2). Despite this hope for future interventions, islet transplantation remains the only therapeutic option currently available for individuals with established type 1 diabetes when insulin therapy fails to maintain adequate metabolic control (3). Islet allograft transplantation has demonstrated great success in terms of restoring normoglycemia (4). Unfortunately, the long-term efficacy following transplantation has been limited due to chronic graft rejection (5). Thus, an optimal approach would involve an islet transplantation protocol that would prevent graft rejection without the need for potentially dangerous long-term and nonspecific immune suppression.
Mesenchymal stem cells (MSCs) have been proposed to be one possible means to enhance current islet transplantation protocols . MSCs represent a population of nonhematopoetic precursor cells that have generated marked interest and attention for their capacity to elicit tissue regeneration (7–9). For the treatment of type 1 diabetes, the therapeutic potential of MSCs is potentially twofold. First, these cells are reported to provide critical growth factors for tissue regeneration . Second, these cells possess potent immunoregulatory properties that could be exploited to suppress allograph rejection following transplantation . 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 原文，很抱歉，贴到糖尿病一级预防的贴纸下面去了。
Mesenchymal Stem Cells Prevent the Rejection of Fully Allogenic Islet Grafts by the Immunosuppressive Activity of Matrix Metalloproteinase-2 and -9
Mesenchymal stem cells (MSCs) were first isolated from bone marrow as stromal cells with characteristics of clonal expansion and were later identified as multipotent stem cells with the capability to differentiate into various kinds of mesodermal tissues (1–3). Aside from their roles in contributing to local microenvironments and supporting hematopoiesis in bone marrow (4–6), MSCs can suppress T-cell proliferation in response to nominal antigens or alloantigens (7). MSC-mediated inhibition is also associated with a reduction in inflammatory cytokine production .
OBJECTIVE Mesenchymal stem cells (MSCs) are known to be capable of suppressing immune responses, but the molecular mechanisms involved and the therapeutic potential of MSCs remain to be clarified.
RESEARCH DESIGN AND METHODS We investigated the molecular mechanisms underlying the immunosuppressive effects of MSCs in vitro and in vivo.
RESULTS Our results demonstrate that matrix metalloproteinases (MMPs) secreted by MSCs, in particular MMP-2 and MMP-9, play an important role in the suppressive activity of MSCs by reducing surface expression of CD25 on responding T-cells. Blocking the activity of MMP-2 and MMP-9 in vitro completely abolished the suppression of T-cell proliferation by MSCs and restored T-cell expression of CD25 as well as responsiveness to interleukin-2. In vivo, administration of MSCs significantly reduced delayed-type hypersensitivity responses to allogeneic antigen and profoundly prolonged the survival of fully allogeneic islet grafts in transplant recipients. Significantly, these MSC-mediated protective effects were completely reversed by in vivo inhibition of MMP-2 and MMP-9.
CONCLUSIONS We demonstrate that MSCs can prevent islet allograft rejection leading to stable, long-term normoglycemia. In addition, we provide a novel insight into the mechanism underlying the suppressive effects of MSCs on T-cell responses to alloantigen. Mesenchymal Stem Cells Prevent the Rejection of Fully Allogenic Islet Grafts by the Immunosuppressive Activity of Matrix Metalloproteinase-2 and -9
间质干细胞可预防全胰岛细胞异体移植中基质金属蛋白酶-2和-9免疫抑制活性的排斥反应
Mesenchymal stem cells (MSCs) were first isolated from bone marrow as stromal cells with characteristics of clonal expansion and were later identified as multipotent stem cells with the capability to differentiate into various kinds of mesodermal tissues (1–3). Aside from their roles in contributing to local microenvironments and supporting hematopoiesis in bone marrow (4–6), MSCs can suppress T-cell proliferation in response to nominal antigens or alloantigens (7). MSC-mediated inhibition is also associated with a reduction in inflammatory cytokine production 。
间质干细胞（MSCs）首次由骨髓中被作为具有克隆分化扩增特性的基质细胞分离，随后被鉴别为具有分化为多种不同中胚层组织能力的多能干细胞。除了能对周围微环境及骨髓造血有支持作用，它还能抑制对所谓抗原或异体抗原有反应的T细胞的增殖。MSC介导的抑制同时也和炎症细胞因子产生的减少相关。
阅读本文的人还阅读：
作者:admin@医学,生命科学 2010-11-09 05:11
医学,生命科学网