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Updated: Dec 17, 2025

Author Spotlight: Advancements and Challenges in β-Cells Differentiation from Pluripotent Stem Cells
Published on: February 2, 2024
Emerging routes to the generation of functional β-cells for diabetes mellitus cell therapy
Gopika G Nair1, Emmanuel S Tzanakakis2,3, Matthias Hebrok4
1Diabetes Center, University of California San Francisco, San Francisco, CA, USA.
Abstract:
Diabetes mellitus, which affects more than 463 million people globally, is caused by the autoimmune ablation or functional loss of insulin-producing β-cells, and prevalence is projected to continue rising over the next decades. Generating β-cells to mitigate the aberrant glucose homeostasis manifested in the disease has remained elusive. Substantial advances have been made in producing mature β-cells from human pluripotent stem cells that respond appropriately to dynamic changes in glucose concentrations in vitro and rapidly function in vivo following transplantation in mice. Other potential avenues to produce functional β-cells include: transdifferentiation of closely related cell types (for example, other pancreatic islet cells such as α-cells, or other cells derived from endoderm); the engineering of non-β-cells that are capable of modulating blood sugar; and the construction of synthetic 'cells' or particles mimicking functional aspects of β-cells. This Review focuses on the current status of generating β-cells via these diverse routes, highlighting the unique advantages and challenges of each approach. Given the remarkable progress in this field, scalable bioengineering processes are also discussed for the realization of the therapeutic potential of derived β-cells.
Insights
Generating functional beta-cells for diabetes treatment shows promise. Advances in stem cell therapy and other innovative methods offer new hope for restoring glucose homeostasis in millions worldwide.
Area of Science:
- Endocrinology and Regenerative Medicine
- Stem Cell Biology
- Bioengineering
Background:
- Diabetes mellitus affects over 463 million globally, characterized by beta-cell loss and impaired glucose homeostasis.
- Generating functional insulin-producing beta-cells remains a significant challenge in diabetes treatment.
- Current research explores multiple avenues to create functional beta-cells for therapeutic applications.
Purpose of the Study:
- To review the current status and diverse approaches for generating functional beta-cells.
- To highlight the advantages and challenges associated with each generation method.
- To discuss scalable bioengineering processes for therapeutic beta-cell realization.
Main Methods:
- Generation of mature beta-cells from human pluripotent stem cells (hPSCs).
- Transdifferentiation of other pancreatic islet cells (e.g., alpha-cells) or endoderm-derived cells.
- Engineering of non-beta-cells for blood sugar modulation and creation of synthetic 'cells'.
Main Results:
- hPSC-derived beta-cells demonstrate appropriate glucose responsiveness in vitro and in vivo functionality post-transplantation.
- Progress has been made in transdifferentiation and cell engineering strategies.
- Scalable bioengineering solutions are being developed to enable therapeutic use.
Conclusions:
- Significant advances in beta-cell generation offer potential for diabetes therapy.
- Diverse strategies, including stem cell-based and synthetic approaches, are advancing the field.
- Bioengineering innovations are crucial for translating derived beta-cells into effective treatments.
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