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聚合物支架在两种 1 型糖尿病模型中,在远离胰腺的部位将健康状态与疾病状态区分开来。

Polymer scaffolds delineate healthy from diseased states at sites distal from the pancreas in two models of type 1 diabetes.

机构信息

Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.

Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan, USA.

出版信息

Biotechnol Bioeng. 2024 Nov;121(11):3600-3613. doi: 10.1002/bit.28824. Epub 2024 Jul 31.

Abstract

Type 1 diabetes (T1D) prevention is currently limited by the lack of diagnostic tools able to identify disease before autoimmune destruction of the pancreatic β cells. Autoantibody tests are used to predict risk and, in combination with glucose dysregulation indicative of β cell loss, to determine administration of immunotherapies. Our objective was to remotely identify immune changes associated with the disease, and we have employed a subcutaneously implanted microporous poly(e-caprolactone) (PCL) scaffold to function as an immunological niche (IN) in two models of T1D. Biopsy and analysis of the IN enables disease monitoring using transcriptomic changes at a distal site from autoimmune destruction of the pancreas, thereby gaining cellular level information about disease without the need for a biopsy of the native organ. Using this approach, we identified gene signatures that stratify healthy and diseased mice in both an adoptive transfer model and a spontaneous onset model of T1D. The gene signatures identified herein demonstrate the ability of the IN to identify immune activation associated with diabetes across models.

摘要

1 型糖尿病(T1D)的预防目前受到缺乏能够在胰腺β细胞自身免疫破坏之前识别疾病的诊断工具的限制。自身抗体检测用于预测风险,并与葡萄糖调节异常(提示β细胞丧失)结合,以确定免疫疗法的应用。我们的目标是远程识别与疾病相关的免疫变化,并采用皮下植入的多孔聚(己内酯)(PCL)支架作为两种 T1D 模型中的免疫生态位(IN)。通过对 IN 的活检和分析,可以使用远离胰腺自身免疫破坏的远端部位的转录组变化进行疾病监测,从而在无需对天然器官进行活检的情况下获得关于疾病的细胞水平信息。使用这种方法,我们在 T1D 的过继转移模型和自发性发病模型中确定了能够将健康和患病小鼠分层的基因特征。本文中确定的基因特征证明了 IN 能够识别与不同模型中糖尿病相关的免疫激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82e/11839227/731ef10042fa/nihms-2055040-f0001.jpg

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