# Engineering Stem Cells for Islet Replacement Therapy: Recent Advances and Barriers for Clinical Translation

## TL;DR

This paper reviews recent progress and challenges in using stem cells to create insulin-producing cells for treating diabetes.

## Contribution

The paper provides an updated review of engineering strategies and translational barriers in stem cell-based islet replacement therapy.

## Key findings

- Stem cells can be engineered to produce glucose-responsive β-like cells.
- Challenges include functional maturation, immune protection, and scalable manufacturing.
- Translational barriers such as durable clinical engraftment remain unresolved.

## Abstract

Diabetes mellitus remains a leading cause of morbidity worldwide, driven in type 1 diabetes by autoimmune destruction of pancreatic β-cells and in advanced type 2 diabetes by progressive β-cell dysfunction and failure. Diabetes affects around 830 million people globally, with the vast majority residing within low- and middle-income nations. Over the last few decades, the numbers of people who have diabetes and those with untreated diabetes have consistently increased. Although current pharmacologic therapies improve glycemic control, they do not restore functional β-cell mass. Consequently, strategies aimed at protecting, regenerating, or replacing insulin-producing cells have emerged as a major focus of regenerative medicine. Stem cell-based approaches offer the potential to generate renewable sources of glucose-responsive β-like cells, but challenges remain in achieving full functional maturation, immune protection, scalable manufacturing, and durable clinical engraftment. This review examines advances in engineering stem cell-derived insulin-producing cells for islet replacement therapy, with an emphasis on differentiation strategies, immunoprotective approaches, and the translational barriers that must be addressed for durable β-cell replacement.