Abstract

Research studies centered on the biology, regeneration, and transplantation of islets continue to shed significant understanding on the development of different forms of diabetes and provide further impetus for the quest to find a “cure.” Diabetes is a manifestation of an inadequate mass of insulin-producing pancreatic beta-cells. While type 1 is characterized by complete loss of beta-cells due to autoimmune attack on them, type 2 is characterized by a relative deficiency of beta-cells due to a decreased compensation for insulin resistance [1, 2]. Restoring beta-cell mass and reversing diabetes can be accomplished by two approaches: either by endogenous regeneration of beta-cells or transplantation of beta-cells from exogenous sources; recent advancements in science and technology have facilitated progress in both. In the first approach, while efforts to expand mature beta-cells in vitro have been met with limited success, regeneration of beta-cells from embryonic and adult stem cells, or pancreatic progenitor cells, has shown promise [2]. Understanding the role of beta-cell-specific transcription factors in the transdifferentiation to beta-cell phenotype is critical to further progress. Pharmacological approaches, employing growth factors, hormones, and small molecules, have also been shown to boost beta-cell proliferation and function.

Highlights

  • In this special issue, substantial developments made in different research areas aimed at overcoming current limitations of islet regeneration and transplantation are presented

  • Gene therapy offers a powerful tool to engineer islet grafts to become resistant to apoptosis induced by inflammation and produce immunosuppressive molecules to attenuate Tcell response

  • The potential to develop patientspecific, autologous beta-cell replacement therapy by using iPSC-derived pancreatic beta-like cells is discussed. Key issues in this field which are presented in this paper include (i) duration and expression levels of targeted genes in islets, (ii) use of viral vectors for direct gene therapy that could lead to insertional mutagenesis and host immunogenicity, International Journal of Endocrinology and (iii) poor efficiency of differentiation of insulin-secreting cells from stem cells

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Summary

Introduction

Substantial developments made in different research areas aimed at overcoming current limitations of islet regeneration and transplantation are presented. Transplantation of isolated islets from cadaveric donor pancreas has proved to be an immediate and effective method for replacing depleted beta-cells in type 1 diabetic patients, allowing them to achieve independence from exogenous insulin administration [3, 4]. To preserve the transplanted beta-cell mass, islet transplant recipients require immunosuppression, which, under current regimens, are known to be beta-cell toxic.

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