From islet transplantation to beta-cell regeneration: an update on beta-cell-based therapeutic approaches in type 1 diabetes

ABSTRACT

Introduction

Type 1 diabetes (T1D) mellitus is an autoimmune disease in which immune cells, predominantly effector T cells, destroy insulin-secreting beta-cells. Beta-cell destruction led to various consequences ranging from retinopathy and nephropathy to neuropathy. Different strategies have been developed to achieve normoglycemia, including exogenous glucose compensation, whole pancreas transplantation, islet transplantation, and beta-cell replacement.

Areas covered

The last two decades of experience have shown that indigenous glucose compensation through beta-cell regeneration and protection is a peerless method for T1D therapy. Tremendous studies have tried to find an unlimited source for beta-cell regeneration, on the one hand, and beta-cell protection against immune attack, on the other hand. Recent advances in stem cell technology, gene editing methods, and immune modulation approaches provide a unique opportunity for both beta-cell regeneration and protection.

Expert opinion

Pluripotent stem cell differentiation into the beta-cell is considered an unlimited source for beta-cell regeneration. Devising engineered pancreas-specific regulatory T cells using Chimeric Antigen Receptor (CAR) technology potentiates an effective immune tolerance induction for beta-cell protection. Beta-cell regeneration using pluripotent stem cells and beta-cell protection using pancreas-specific engineered regulatory T cells promises to develop a curative protocol in T1D.

KEYWORDS:

• Beta-cell regeneration
• beta-cell protection
• immune modulation
• stem cell differentiation
• type 1 diabetes

Article highlights

• Two-decade research has shown that indigenous insulin compensation using beta-cell replacement is the irreplaceable approach in T1D therapy.

• Since T1D is primarily an autoimmune disease, beta-cell protection against immune attack is as necessary as beta-cell compensation through beta-cell regeneration.

• Pluripotent stem cells are an unlimited source for beta-cell regeneration, and durable immune modulation could lead to an immune tolerance induction in T1D mellitus.

• Pancreas-specific immune tolerance induction is the best approach for beta-cell protection against immune attack. The pancreas-specific engineered regulatory T cell is an example of pancreas-specific immune tolerance induction. Theoretically, it can be more developed and used for this purpose.

• Combining beta-cell regeneration using pluripotent stem cells and beta-cell protection using tolerance inductions via innovative methods like pancreas-specific engineered regulatory T cells promises to develop a new curative protocol for T1D.

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.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.