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ISLET TRANSPLANTATION

I’ve got you under my skin

Nature Metabolism volume 2, pages 993–994 (2020)Cite this article

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Islet of Langerhans transplantation as a cell therapy for type 1 diabetes faces obstacles that have prevented full and lasting engraftment in the liver, the currently preferred implantation site in clinical practice. Yu and colleagues circumvent these issues and achieve stable diabetes reversal by transplanting islets encapsulated in a simple collagen-based matrix into the more accessible subcutaneous space.

Replacement of the β-cells destroyed by autoimmunity is considered the strategy that comes closest to a ‘cure’ for people with type 1 diabetes. β-cell replacement can be achieved by transplanting either the whole pancreas or isolated islets of Langerhans from organ donors. Whereas pancreatic transplantation has excellent long-term functional results, at the cost of high perioperative morbidity, islet transplantation is a minimally invasive procedure but faces the issues of poor engraftment and attrition of graft function1. Several mechanisms contribute to these problems, most notably (1) damage sustained by the islets during the isolation procedure, (2) a proinflammatory microenvironment at the site of engraftment and (3) immune reaction from the host against the graft. Briefly, (1) the isolation procedure disrupts the islets from their surrounding extracellular matrix (ECM) and disconnects their intrinsic vascular bed; (2) islets are transplanted into the liver through injection into the portal system, thus eliciting cascades of inflammatory events, most notoriously the instant blood-mediated inflammatory reaction (IBMIR), and leading to the destruction of a sizeable proportion of the implanted islets in the subsequent hours or days; (3) in clinical settings, lifelong immunosuppressive therapy is necessary to protect the islets from both allogeneic rejection and recurrence of autoimmunity1. Consequently, multiple donors are necessary to transplant enough islets to achieve insulin independence, and more than half of all patients return to exogenous insulin in the first 5 years after transplantation2.

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Fig. 1: Transplantation of islets of Langerhans in the subcutaneous site: how it works and how it can develop.

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Acknowledgements

This work is supported by grants from the Swiss National Science Foundation (grant 310030_173138), the European Foundation for the Study of Diabetes (EFSD), the European Commission (Horizon 2020 Framework Program; VANGUARD grant 874700), the Juvenile Diabetes Research Foundation (JDRF; grant 3-SRA-2020-926-S-B) and the Shota Rustaveli National Science Foundation (grant FR-19-19760).

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Affiliations

  1. Cell Isolation and Transplantation Center, Department of Surgery, University of Geneva School of Medicine, Geneva, Switzerland

    Thierry Berney & Ekaterine Berishvili

  2. Division of Transplantation, Department of Surgery, University of Geneva Hospitals, Geneva, Switzerland

    Thierry Berney

  3. Faculty Diabetes Center, University of Geneva School of Medicine, Geneva, Switzerland

    Thierry Berney & Ekaterine Berishvili

  4. Institute of Medical and Public Health Research, Ilia State University, Tbilisi, Georgia

    Ekaterine Berishvili

Authors
  1. Thierry Berney
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  2. Ekaterine Berishvili
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Both authors contributed equally to the writing of the manuscript.

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Correspondence to Thierry Berney.

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The authors declare no competing interests.

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Berney, T., Berishvili, E. I’ve got you under my skin. Nat Metab 2, 993–994 (2020). https://doi.org/10.1038/s42255-020-0268-8

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