Polymer scaffolds delineate healthy from diseased states at sites distal from the pancreas in two models of type 1 diabetes.
Autor: | King JL; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA., Urie RR; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA., Morris AH; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.; Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan, USA., Rad L; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA., Bealer E; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA., Kasputis T; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA., Shea LD; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.; Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.; Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, USA. |
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Jazyk: | angličtina |
Zdroj: | Biotechnology and bioengineering [Biotechnol Bioeng] 2024 Nov; Vol. 121 (11), pp. 3600-3613. Date of Electronic Publication: 2024 Jul 31. |
DOI: | 10.1002/bit.28824 |
Abstrakt: | 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. (© 2024 The Author(s). Biotechnology and Bioengineering published by Wiley Periodicals LLC.) |
Databáze: | MEDLINE |
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