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

• Published in: Biotechnology and bioengineering 2024-11, Vol.121 (11), p.3600-3613
• Main Authors: King, Jessica L., Urie, Russell R., Morris, Aaron H., Rad, Laila, Bealer, Elizabeth, Kasputis, Tadas, Shea, Lonnie D.
• Format: Article
• Language: English
• Subjects: Adoptive transfer; Animal models; Autoantibodies; Beta cells; Biopsy; Destruction; Diabetes; Diabetes mellitus (insulin dependent); gene signatures; Immune response; immunological niche; Immunology; Immunotherapy; Pancreas; Polymers; Scaffolds; Signatures; Transcriptomics; type 1 diabetes
• ISSN: 0006-3592; 1097-0290; 1097-0290
• DOI: 10.1002/bit.28824

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. A subcutaneous scaffold was employed as an immunological niche (IN) to enable disease monitoring in two models of type 1 diabetes (T1D). King et al. utilized IN biopsies to identify gene signatures that capture the transcriptomic changes that stratify healthy and diseased mice in both an adoptive transfer and a spontaneous onset model of T1D. The novel gene signatures demonstrate the ability of the IN to capture systemic immune activation associated with T1D across models.