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MINI REVIEW article

Front. Endocrinol.

Sec. Diabetes: Molecular Mechanisms

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1612576

This article is part of the Research TopicAdvances in β-cell Development & RegenerationView all 6 articles

Harnessing Beta-Cell Replication: Advancing Molecular Insights to Regenerative Therapies in Diabetes

Provisionally accepted
  • City of Hope National Medical Center, Duarte, United States

The final, formatted version of the article will be published soon.

Diminished functional beta-cell mass is a key pathogenic mechanism underlying both type 1 and type 2 diabetes (T1D and T2D), precipitated by the progressive impairment of insulin secretion, loss of cellular identity, and ultimately, beta-cell death. The replenishment of beta-cell deficit through the transplantation of pancreatic islets from cadaveric donors or beta-cells derived from human embryonic stem cells has shown transformative therapeutic potential. However, the regeneration of functional beta-cell mass in vivo remains an important therapeutic goal, as a more physiological and scalable approach. Effective beta-cell replenishment must address the underlying causes of beta-cell loss, such as cellular stress and autoimmunity, while simultaneously promoting beta-cell regeneration, function, and survival. Advances in the mechanistic underpinnings of beta-cell differentiation, growth, and survival, coupled with cutting-edge high-throughput screening methods have accelerated the discovery of novel therapeutic targets and small-molecule interventions. Current strategies for in vivo beta-cell expansion include modulating the cell-cycle to promote replication, reprogramming non-beta-cell lineages into beta-cells, and enhancing beta-cell survival. However, the limited regenerative capacity and inherently high stress sensitivity of beta-cells pose significant barriers to their in vivo expansion, further complicated by the fundamental conflict between replication and functional maintenance, and the high vulnerability of replicating cells in a metabolically stressed environment. There has been tremendous progress in developing approaches that simultaneously promote beta-cell expansion and function. In this review, we discuss the recent advances in beta-cell expansion, along with remaining challenges and emerging opportunities to address them.

Keywords: beta cells, Replication, proliferation, Regeneration, Therapeutics, diabetes

Received: 15 Apr 2025; Accepted: 04 Jun 2025.

Copyright: © 2025 Dhawan and Vasavada. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Sangeeta Dhawan, City of Hope National Medical Center, Duarte, United States
Rupangi Vasavada, City of Hope National Medical Center, Duarte, United States

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