Title |
Biopatterned CTLA4/Fc Matrices Facilitate Local Immunomodulation, Engraftment, and Glucose Homeostasis After Pancreatic Islet Transplantation
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Published in |
Diabetes, September 2016
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DOI | 10.2337/db16-0320 |
Pubmed ID | |
Authors |
Wensheng Zhang, Vijay S. Gorantla, Phil G. Campbell, Yang Li, Yang Yang, Chiaki Komatsu, Lee E. Weiss, Xin Xiao Zheng, Mario G. Solari |
Abstract |
Pancreatic islet transplantation (PIT) represents a potential therapy to circumvent the need for exogenous insulin in type 1 diabetes. However, PIT remains limited by lack of donor islets and need for long-term multi-drug immunosuppression to prevent alloimmune islet rejection. Our goal was to evaluate a local immunoregulatory strategy that sustains islet allograft survival and restores glucose homeostasis in the absence of systemic immunosuppression. Nanogram quantities of murine CTLA4/Fc fusion protein were controllably delivered within human acellular dermal matrix scaffolds using an inkjet-based biopatterning technology and co-transplanted with allogeneic islets under the renal capsule to create an immunoregulatory microenvironment around the islet allograft. We achieved long-term engraftment of small loads of allogeneic islet cells with 40% of MHC-mismatched mouse recipients maintaining sustained normoglycemia following pancreatic β-cell ablation by streptozotocin. Biopatterned CTLA4/Fc local therapy was associated with expansion of Foxp3(+) regulatory T-cells and shifts in cytokine production and gene expression from pro-inflammatory to regulatory profiles, thus substantially benefiting islet allografts survival and function. This study is a new paradigm for targeted therapies in PIT that demonstrates the favorable effects of immune alterations in the transplant milieu and suggests a unique strategy for minimizing systemic immunosuppression and promoting islet allograft survival. |
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United States | 1 | 50% |
Unknown | 1 | 50% |
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Science communicators (journalists, bloggers, editors) | 1 | 50% |
Members of the public | 1 | 50% |
Mendeley readers
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Unknown | 23 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 6 | 26% |
Researcher | 6 | 26% |
Unspecified | 2 | 9% |
Other | 1 | 4% |
Unknown | 8 | 35% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 5 | 22% |
Engineering | 3 | 13% |
Unspecified | 2 | 9% |
Biochemistry, Genetics and Molecular Biology | 2 | 9% |
Immunology and Microbiology | 1 | 4% |
Other | 2 | 9% |
Unknown | 8 | 35% |