Your new experience awaits. Try the new design now and help us make it even better

REVIEW article

Front. Immunol.

Sec. Alloimmunity and Transplantation

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1625439

This article is part of the Research TopicLocalized Immunomodulation Approaches for Transplantation ToleranceView all 5 articles

Navigating challenges in human pluripotent stem cell islet therapy

Provisionally accepted
Mohammed UsamaMohammed Usama1,2Ying DengYing Deng1,3Yiran ChenYiran Chen1Théa MillandThéa Milland1,3Mohan MalleshaiahMohan Malleshaiah1,2,4Yasaman AghazadehYasaman Aghazadeh1,2,5*
  • 1Montreal Clinical Research Institute (IRCM), Montréal, Canada
  • 2McGill University, Department of Medicine, Division of Experimental Medicine, Montreal, Canada
  • 3University of Montreal, Department of Medicine, Molecular Biology, Montreal, Canada
  • 4University of Montreal, Department of Biochemistry and Molecular Medicine, Montreal, Canada
  • 5University of Montreal, Department of Medicine, Montreal, Canada

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

Select one of your emails

You have multiple emails registered with Frontiers:

Notify me on publication

Please enter your email address:

If you already have an account, please login

You don't have a Frontiers account ? You can register here

In the past two decades, several tissues have been generated from the differentiation of human pluripotent stem cells (hPSCs) to model development or disease, and for use in drug testing and cell replacement therapies. A frontliner of hPSC-derived tissues used in cell replacement therapies are the pancreatic cells, which have entered multiple clinical trials since 2014 for the treatment of type 1 diabetes (T1D). Despite challenges in early trials, the detection of endogenous C-peptide in recipients was encouraging. The results and challenges of these trials inspired new areas of research, leading to incremental advances in cell differentiation and delivery technologies, and a deeper understanding of the transplantation microenvironment to enhance therapeutic efficacy and longevity. Reports from the most recent trials demonstrated success in reducing or eliminating exogenous insulin administration for people with T1D, increasing hope for a cure for T1D via regenerative medicine. Recent efforts can be broadly categorized into: (1) improving the cell product as surrogates of native beta cells, (2) promoting engraftment post-transplant to support cell survival, integration into the host, and endocrine function, and (3) developing immunomodulation strategies to reduce or circumvent immunosuppression regimen. In this review, we discuss recent and emerging advances in these three areas and the potential, risk, and scalability of experimental models to the clinic.

Keywords: beta cells, islets, Transplantation, Human pluripotent stem cells, vascularization, immune cells

Received: 09 May 2025; Accepted: 16 Jul 2025.

Copyright: © 2025 Usama, Deng, Chen, Milland, Malleshaiah and Aghazadeh. 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: Yasaman Aghazadeh, Montreal Clinical Research Institute (IRCM), Montréal, Canada

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material