Navigating challenges in human pluripotent stem cell-derived islet therapy for type 1 diabetes
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 p...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1625439/full |
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| author | Mohammed Usama Mohammed Usama Ying Deng Ying Deng Yiran Chen Théa Milland Théa Milland Mohan Malleshaiah Mohan Malleshaiah Mohan Malleshaiah Yasaman Aghazadeh Yasaman Aghazadeh Yasaman Aghazadeh |
| author_facet | Mohammed Usama Mohammed Usama Ying Deng Ying Deng Yiran Chen Théa Milland Théa Milland Mohan Malleshaiah Mohan Malleshaiah Mohan Malleshaiah Yasaman Aghazadeh Yasaman Aghazadeh Yasaman Aghazadeh |
| author_sort | Mohammed Usama |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1bce72497a6d48dc8e05eb06a1870b0c |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-1bce72497a6d48dc8e05eb06a1870b0c2025-08-20T03:57:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16254391625439Navigating challenges in human pluripotent stem cell-derived islet therapy for type 1 diabetesMohammed Usama0Mohammed Usama1Ying Deng2Ying Deng3Yiran Chen4Théa Milland5Théa Milland6Mohan Malleshaiah7Mohan Malleshaiah8Mohan Malleshaiah9Yasaman Aghazadeh10Yasaman Aghazadeh11Yasaman Aghazadeh12Institute de Recherches Cliniques de Montréal (IRCM), Montréal, QC, CanadaDivision of Clinical and Translational Research, Department of Medicine, McGill University, Montréal, QC, CanadaInstitute de Recherches Cliniques de Montréal (IRCM), Montréal, QC, CanadaDepartment of Medicine, University of Montréal, Montréal, QC, CanadaInstitute de Recherches Cliniques de Montréal (IRCM), Montréal, QC, CanadaInstitute de Recherches Cliniques de Montréal (IRCM), Montréal, QC, CanadaDepartment of Anatomy and Cell Biology, McGill University, Montréal, QC, CanadaInstitute de Recherches Cliniques de Montréal (IRCM), Montréal, QC, CanadaDivision of Clinical and Translational Research, Department of Medicine, McGill University, Montréal, QC, CanadaDepartment of Biochemistry and Molecular Medicine, University of Montréal, Montréal, QC, CanadaInstitute de Recherches Cliniques de Montréal (IRCM), Montréal, QC, CanadaDivision of Clinical and Translational Research, Department of Medicine, McGill University, Montréal, QC, CanadaDepartment of Medicine, University of Montréal, Montréal, QC, CanadaIn 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1625439/fullbeta cellsisletstransplantationhuman pluripotent stem cellsvascularizationimmune cells |
| spellingShingle | Mohammed Usama Mohammed Usama Ying Deng Ying Deng Yiran Chen Théa Milland Théa Milland Mohan Malleshaiah Mohan Malleshaiah Mohan Malleshaiah Yasaman Aghazadeh Yasaman Aghazadeh Yasaman Aghazadeh Navigating challenges in human pluripotent stem cell-derived islet therapy for type 1 diabetes Frontiers in Immunology beta cells islets transplantation human pluripotent stem cells vascularization immune cells |
| title | Navigating challenges in human pluripotent stem cell-derived islet therapy for type 1 diabetes |
| title_full | Navigating challenges in human pluripotent stem cell-derived islet therapy for type 1 diabetes |
| title_fullStr | Navigating challenges in human pluripotent stem cell-derived islet therapy for type 1 diabetes |
| title_full_unstemmed | Navigating challenges in human pluripotent stem cell-derived islet therapy for type 1 diabetes |
| title_short | Navigating challenges in human pluripotent stem cell-derived islet therapy for type 1 diabetes |
| title_sort | navigating challenges in human pluripotent stem cell derived islet therapy for type 1 diabetes |
| topic | beta cells islets transplantation human pluripotent stem cells vascularization immune cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1625439/full |
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