Key Matrix Proteins Within the Pancreatic Islet Basement Membrane Are Differentially Digested During Human Islet Isolation.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 100968638 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-6143 (Electronic) Linking ISSN: 16006135 NLM ISO Abbreviation: Am J Transplant Subsets: MEDLINE
    • Publication Information:
      Publication: 2023- : [New York] : Elsevier
      Original Publication: Copenhagen : Munksgaard International Publishers, 2001-
    • Subject Terms:
      Cell Separation*; Basement Membrane/*metabolism ; Collagen Type IV/*metabolism ; Heparan Sulfate Proteoglycans/*metabolism ; Islets of Langerhans/*metabolism ; Laminin/*metabolism ; Membrane Proteins/*metabolism; Adult ; Cells, Cultured ; Female ; Humans ; Islets of Langerhans/cytology ; Islets of Langerhans Transplantation ; Male ; Middle Aged
    • Abstract:
      Clinical islet transplantation achieves insulin independence in selected patients, yet current methods for extracting islets from their surrounding pancreatic matrix are suboptimal. The islet basement membrane (BM) influences islet function and survival and is a critical marker of islet integrity following rodent islet isolation. No studies have investigated the impact of islet isolation on BM integrity in human islets, which have a unique duplex structure. To address this, samples were taken from 27 clinical human islet isolations (donor age 41-59, BMI 26-38, cold ischemic time < 10 h). Collagen IV, pan-laminin, perlecan and laminin-α5 in the islet BM were significantly digested by enzyme treatment. In isolated islets, laminin-α5 (found in both layers of the duplex BM) and perlecan were lost entirely, with no restoration evident during culture. Collagen IV and pan-laminin were present in the disorganized BM of isolated islets, yet a significant reduction in pan-laminin was seen during the initial 24 h culture period. Islet cytotoxicity increased during culture. Therefore, the human islet BM is substantially disrupted during the islet isolation procedure. Islet function and survival may be compromised as a consequence of an incomplete islet BM, which has implications for islet survival and transplanted graft longevity.
      (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)
    • Grant Information:
      110126/Z/15/Z United Kingdom WT_ Wellcome Trust
    • Contributed Indexing:
      Keywords: basic (laboratory) research/science; clinical research/practice; islet isolation; islet transplantation; islets of Langerhans
    • Accession Number:
      0 (Collagen Type IV)
      0 (Heparan Sulfate Proteoglycans)
      0 (Laminin)
      0 (Membrane Proteins)
      0 (laminin alpha5)
      143972-95-6 (perlecan)
    • Publication Date:
      Date Created: 20160727 Date Completed: 20171211 Latest Revision: 20230124
    • Publication Date:
      20240829
    • Accession Number:
      10.1111/ajt.13975
    • Accession Number:
      27456745