Regenerating β cells of the pancreas – potential developments in diabetes treatment

ABSTRACT

Introduction: The etiology of diabetes is mainly attributed to insulin deficiency due to the lack of β cells (type 1), or to insulin resistance that eventually results in β cell dysfunction (type 2). Therefore, an ultimate cure for diabetes requires the ability to replace the lost insulin-secreting β cells. Strategies for regenerating β cells are under extensive investigation.

Areas covered: Herein, the authors first summarize the mechanisms underlying embryonic β cell development and spontaneous adult β cell regeneration, which forms the basis for developing β cell regeneration strategies. Then the rationale and progress of each β cell regeneration strategy is reviewed. Current β cell regeneration strategies can be classified into two main categories: in vitro β cell regeneration using pluripotent stem cells and in vivo reprogramming of non-β cells into β cells. Each has its own advantages and disadvantages.

Expert opinion: Regenerating β cells has shown its potential as a cure for the treatment of insulin-deficient diabetes. Much progress has been made, and β cell regeneration therapy is getting closer to a clinical reality. Nevertheless, more hurdles need to be overcome before any of the strategies suggested can be fully translated from bench to bedside.

KEYWORDS:

• β Cell regeneration
• diabetes
• stem cells
• reprogramming

Article highlights

• An ultimate cure for type 1 diabetes requires the replacement of the lost β cells, and many progresses have been made in search of strategies to regenerate β cells to date.

• Current β cell regeneration strategies can be classified into two categories: in vitro β cell regeneration using pluripotent stem cells, and in vivo reprogramming of non-β cells into β cells.

• In vitro regeneration of β cells has been explored with human pancreatic stem cells, human embryonic stem cells, and human induced pluripotent cells. An efficient and scalable in vitro β cell differentiation protocol has been developed.

• The development of efficient β cell differentiation protocol and implementation of islet encapsulation devices have helped to move stem cell-based β cell regeneration strategy from preclinical to clinical studies.

• In vivo regeneration of β cells are focused on reprogramming of non-β cells into β cells. Four types of tissues/cells have been explored in preclinical studies, which include liver cells, gut cells, pancreatic exocrine cells, and islet α cells.

• β cell regeneration strategies have shown their potential for the treatment of insulin-deficient diabetes, but more hurdles need to be overcome before they can be fully translated from bench to bedside.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This project was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants [DK081463 and DK107412].