Quality control strategy for differentiating induced pluripotent stem cells into pancreatic β-cells before transplantation

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of pancreatic β-cells and the subsequent loss of insulin production. The regeneration of pancreatic β-cells from induced pluripotent stem cells (iPSCs) represents a promising therapeutic approach for restoring β-cell function in T1DM patients. However, ensuring the safety, functionality, and genetic stability of iPSC-derived β-cells is crucial for their clinical application. To address this challenge, a comprehensive literature review was conducted using PubMed/MEDLINE, Web of Science, and Scopus databases to identify relevant studies published up to October 2025. It included an analysis of key regulatory documents from the U.S. Food and Drug Administration (FDA), the European Medicines Agency on Advanced Therapy Medicinal Products (EMA ATMP), and the International Organization for Standardization (ISO). This article proposes a comprehensive quality control (QC) strategy for differentiating iPSCs into pancreatic β-cells, emphasizing a tiered approach with multiple checkpoints throughout the process. The strategy integrates advanced molecular and functional assays to evaluate cell identity, viability, stability, and microbiological safety. The proposed QC framework allows for continuous monitoring, early detection of potential issues, and real-time adjustments to optimize the differentiation process. The flexibility of this approach ensures its adaptation to emerging scientific advancements and regulatory requirements. This integrated and adaptable QC strategy enhances the likelihood of success in generating functional β-cells, laying a solid foundation for the clinical application of iPSC-derived β-cell therapies and offering hope for effective, long-term treatments for T1DM. Type 1 diabetes (T1DM) is a disease in which the immune system destroys the β-cells of the pancreas, which produce insulin. Without insulin, the body cannot control blood sugar levels, so patients with T1DM depend on insulin injections for life. Although needed, this treatment cannot cure the disease or replace lost β-cells. A promising area of research is the development of methods to generate β-cells from induced pluripotent stem cells (iPSCs). These stem cells are created by reprogramming a patient’s own blood or skin cells. This process turns them back into a stem-cell-like state, allowing them to develop into almost any cell type in the body. Scientists can guide iPSCs to develop into pancreatic β-cells, which can one day be transplanted to produce natural insulin. However, before these cells can be safely used in patients, researchers must confirm that they are healthy, functioning correctly, and free of risks such as genetic changes or contamination. In this article, we present a comprehensive quality control (QC) strategy to assess iPSCs and their conversion to β-cells at various developmental stages. The QC includes confirming their identity, genetic stability, function, and clinical safety. Our proposed QC method represents a step-by-step safety measure that flags issues early and allows researchers to adjust the process as needed. This approach could make the production of β-cells safer and more reliable as it continues to be developed for future therapies. The study contributes to advancing long-term therapies that may improve the lives of patients with T1DM.