Alissen Haro
Laboratory Assistant
Instituto de Investigaciones en Biomedicina (iBioMed), USFQ
Quito, Ecuador
ORCID: 0000-0003-1425-8101
Quentin Perrier
PharmD, PhD
Univ. Grenoble Alpes, Pharmacy department, Grenoble Alpes University Hospital
Grenoble, France
Andrés Caicedo
Associate Professor
Universidad San Francisco de Quito (USFQ)
Quito, Ecuador
ORCID: 0000-0001-8821-0333
My first time attending the ISCT Annual Meeting 2025 in New Orleans was an unforgettable and enriching experience. This opportunity was possible thanks to my participation as a South and Central American (SCA) Regional Early Stage Professional (ESP) Subcommittee member. The conference opened my mind to new perspectives and research topics that we could implement in Latin America in the future. Furthermore, I had the chance to learn about innovative research projects and the brilliant scientists behind them.
I attended visionary and fascinating sessions, roundtables, and workshops. From “ISCT Immune Monitoring and Immunobiology Workshop”, to the roundtables “Is Germline Editing Feasible and Should it be Permissible?” and “What Stands in the Way of the RNA Revolution?”, and the inspirational ESP Mentoring Summit – “Building Your Path: Growing Your Future – What Does It Take to Thrive in CGT?”, to the “Exosomes Scientific Signatures Series - Advancing EVs: Overcoming Barriers, Transforming Therapies” sessions. However, one session that stood out to me was the plenary “Coming to the Clinic: T-Cell Receptors, Stem-Cell Derived Islets, and iPSCs”, where Qing Ling, MD from Shanghai Changzheng Hospital, China, presented about Stem-Cell Derived Islet (SC-islets) Transplantation in Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D). Her presentation clarified how regenerative medicine is evolving into clinical applications and shifting the paradigms in chronic diseases like diabetes.
Allogeneic cell-based therapies are gaining momentum in regenerative medicine, providing scalable and ready-to-use treatment options for various medical conditions. In the context of T1D, allogeneic islet transplantation offers a potentially more effective regenerative approach than conventional insulin therapy supported by technological devices. However, its widespread clinical use is hindered by the need for pancreas donation from deceased donors, which limits the availability and scalability of this therapy. Given the rising incidence of both T1D and T2D, exploring alternative cellular sources to restore endogenous insulin production has become a pressing need. Although xenotransplantation has shown some success in kidney transplantation, ethical concerns remain a significant barrier. In this context, the development of SC–islets represents a promising avenue, with continuous advancements since their first reported generation around 2007 [1].
Recently, Wang and colleagues [2] reported a phase 1 clinical trial with promising results in a patient with T1D, in which autologous transplantation of chemically induced pluripotent stem-cell-derived (CiPSC) islets beneath the abdominal anterior rectus sheath led to the restoration of exogenous insulin-independent glycemic control. The research team followed the patient for 1 year and noticed marked improvements four months post-transplant, where the glycemic range increased from 43.18% (baseline) to 96.21%. A similar case is the study by Wu and team [3]. They used islet tissue (E-islets) generated from autologous human endoderm stem cells (EnSCs) in the first-in-human tissue replacement therapy for a late-stage T2D patient with impaired insulin secretion. The outcomes were remarkable. After the first 27 months post-transplantation, the patient presented significant improvements in glycemic control, good graft tolerance, and no tumor formation.
Both cases demonstrate alternative strategies to allogeneic islet transplantation. Nevertheless, using autologous cells or SC-islets without immunosuppressants to treat T1D may lead to the recurrence of autoimmunity and destruction of the newly implanted graft [2]. Precisely, Dr. Ling emphasized in her presentation that autologous transplantation requires full immunosuppression at the outset to prevent a recurrence of autoimmunity in patients with T1D. This immunosuppressive approach can be evaded whether systemic therapies are applied to control the autoimmune response or donor cells are genetically modified to resist it. In contrast, the E-islets transplantation has shown promising results in T2D treatment. However, more trials in T1D patients, as well as an increase in sample size, are needed to validate its potential. Additionally, Vertex Pharmaceuticals started a phase 3 clinical trial on not fully mature allogenic stem-cell-derived islets in a macro device (NCT04786262, NCT06832410) [4]. However, we should acknowledge that the opacity around the information about the content of the device or the results is questionable.
On the other hand, SC-islets offer several advantages: can be maintained in culture over long periods, provide a reliable and abundant source of cells, can be exposed to different exogenous agents to mimic environmental factors of diabetes pathogenesis, among others. Furthermore, different strategies are being developed to face the challenges of immunosuppression during transplant. These include macroencapsulation of the entire SC-islet transplant, microencapsulation of individual SC-islets using biomaterials, and use of gene editing technology to modify SC-islets [5, 6].
While SC-islets represent a promising therapeutic approach for diabetes treatment, several limitations must still be addressed before these therapies can become widely accessible. Further optimization, improvement, and deep investigation are essential to ensure both safety and efficacy, leading to good practices that focus on the patient's needs, requirements, and quality of life improvement.
Bibliography
[1] Jiang J, Au M, Lu K, Eshpeter A, Korbutt G, Fisk G, et al. Generation of Insulin-Producing Islet-Like Clusters from Human Embryonic Stem Cells. Stem Cells. 2007 May 17;25(8):1940–53. https://doi.org/10.1634/stemcells.2006-0761
[2] Wang S, Du Y, Zhang B, Meng G, Liu Z, Liew SY, et al. Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient. Cell. 2024 Sep 25;187(22):6152-6164.e18. https://doi.org/10.1016/j.cell.2024.09.004
[3] Wu J, Li T, Guo M, Ji J, Meng X, Fu T, et al. Treating a type 2 diabetic patient with impaired pancreatic islet function by personalized endoderm stem cell-derived islet tissue. Cell Discovery. 2024 Apr 30;10(1). https://doi.org/10.1038/s41421-024-00662-3
[4] Vertex announces program updates for Type 1 Diabetes portfolio | Vertex Pharmaceuticals. Vertex Pharmaceuticals. 2025. https://investors.vrtx.com/news-releases/news-release-details/vertex-announces-program-updates-type-1-diabetes-portfolio
[5] Maestas MM, Bui MH, Millman JR. Recent progress in modeling and treating diabetes using stem cell-derived islets. Stem Cells Translational Medicine. 2024 Aug 19;13(10):949–58. https://doi.org/10.1093/stcltm/szae059
[6] Hogrebe NJ, Ishahak M, Millman JR. Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes. Cell Stem Cell. 2023 May 1;30(5):530–48. https://doi.org/10.1016/j.stem.2023.04.002
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