Local Immunomodulatory Strategies to Prevent Allo-Rejection in Transplantation of Insulin-Producing Cells

Adv Sci (Weinh). 2021 Sep;8(17):e2003708. doi: 10.1002/advs.202003708. Epub 2021 Jul 14.

Abstract

Islet transplantation has shown promise as a curative therapy for type 1 diabetes (T1D). However, the side effects of systemic immunosuppression and limited long-term viability of engrafted islets, together with the scarcity of donor organs, highlight an urgent need for the development of new, improved, and safer cell-replacement strategies. Induction of local immunotolerance to prevent allo-rejection against islets and stem cell derived β cells has the potential to improve graft function and broaden the applicability of cellular therapy while minimizing adverse effects of systemic immunosuppression. In this mini review, recent developments in non-encapsulation, local immunomodulatory approaches for T1D cell replacement therapies, including islet/β cell modification, immunomodulatory biomaterial platforms, and co-transplantation of immunomodulatory cells are discussed. Key advantages and remaining challenges in translating such technologies to clinical settings are identified. Although many of the studies discussed are preliminary, the growing interest in the field has led to the exploration of new combinatorial strategies involving cellular engineering, immunotherapy, and novel biomaterials. Such interdisciplinary research will undoubtedly accelerate the development of therapies that can benefit the whole T1D population.

Keywords: biomaterials; cell therapy; drug delivery; immunomodulation; type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / surgery*
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Humans
  • Immunomodulation / immunology*
  • Insulin-Secreting Cells / transplantation*
  • Islets of Langerhans Transplantation / methods*