The wave of regenerative medicine is surging. Pluripotent stem cell therapy, with its huge application potential and the continuous emergence of breakthrough achievements, is rising to become the most sought-after track in the global medical field.

Recently, this cutting-edge field has witnessed a series of exciting advancements - not only have they opened up brand-new treatment paths for many intractable diseases, but they have also injected strong impetus into the development of the entire regenerative medicine, making the hope of conquering difficult and complicated diseases increasingly clear.

01 A complete set of endocrine cell types of islets was constructed

Transplantation of pluripotent stem cell-derived islets (PSC islets) containing functional insulin-secreting β cells is a promising cell therapy for restoring blood sugar control in diabetes.

On August 8, 2025, the team led by Deng Hongkui from Peking University published a research paper online in Cell Stem Cell (IF=20.4). This study successfully differentiated and constructed islets with complete endocrine cell types using human pluripotent stem cells for the first time. These islets can respond efficiently to changes in blood glucose concentration. They not only effectively lower blood sugar but also have a crucial function of raising blood sugar. They have demonstrated effective hypoglycemic protection in diabetic mouse models, solving the problem of incomplete types and functions of islet cells derived from stem cells.

In this study, the team innovatively established an efficient induction protocol for non-β endocrine cells by regulating the activity of acetyltransferase (HAT) P300/CBP through epigenetic small molecules. Combined with reaggregation technology, they successfully constructed a "reconstructed islet" containing all five endocrine subtypes. By regulating the ratio of the five endocrine cells in the reconstructed islets, It has solved the problems of the absence of islet cell types and the imperfection of islet function in the differentiation of pluripotent stem cells. It is worth noting that the strategy of generating β cells and non-β cells respectively from independent "islet buds" and then integrating them into functional islets is similar to the natural development process of human islets, revealing the differentiation rules of functional endocrine cells.

Reconstructed islets with complete endocrine subtypes were constructed in vitro to evaluate the effect of the endocrine composition of islets on blood glucose regulation

The team verified the function of reconstructing pancreatic islets using a type 1 diabetic mouse model and made three important discoveries: 1 For the first time, the quantitative relationship between the composition of pancreatic islet cells and blood glucose levels was clarified, confirming that the reconstructed islets with optimized composition better maintain physiological blood glucose levels. 2. Reveal the hypoglycemic protective function of non-β cells (especially α and δ cells), which can effectively prevent hypoglycemia under conditions of insulin overdose or fasting; 3. The hyperinsulin-hypoglycemic clamp experiment confirmed that the reconstruction of islets can restore the body's hypoglycemic reverse regulatory response, including a more significant "brake" of C-peptide secretion, activation of glucagon secretion, and a synergistic response of reverse regulatory hormones (such as adrenaline).

The reconstructed islets that integrate non-β cells can effectively prevent hypoglycemia and restore the body's reverse regulatory response to hypoglycemia

This study proposes a strategy that functionally generalizes the real islets for bidirectional blood glucose regulation and demonstrates that optimizing the composition of endocrine cells in PSC islets can enhance hypoglycemic protection. This progress provides further safety guarantees for the clinical transformation of stem cell-derived islets and helps accelerate the clinical application process of cell therapy for diabetes.

02 Overall model of embryos in the postproenteral stage

In the field of embryonic development research, obtaining experimental models that can simulate the formation period of key organs in mammals has always been a huge challenge.

Recently, the Oytun Yilmaz team from the Stem Cell Institute of the University of Cambridge published their latest findings in the journal Cell Stem Cell. An overall model of post-progut embryos that can be generated completely without relying on transgenic modification, using only mouse naive embryonic stem cells (naive ESCs) and induced pluripotent stem cells (iPSCs).

This method can reproduce in vitro developmental processes including neural tube formation, body axis elongation and early organogenesis, providing a powerful new tool for understanding the mechanism of early mammalian embryogenesis.

The overall idea of this study is: First, obtain the naive ESCs and iPSCs of mice and maintain their primitive state in a specific culture system; Then, these cells are aggregated in low-adhesion micropores to form cell clusters, and through self-organization, a precursor structure similar to a blastocyst is formed. Subsequently, under the condition of precisely formulated regulatory factors of signal molecules such as Wnt, BMP, and FGF, it was induced to enter the development trajectory of the posterior progut stage. Finally, live cell imaging and immunofluorescence labeling were used to track morphological changes until an overall model with neural plates, body segments and primitive intestinal tubes was formed.

The greatest advantage of this system lies in its simplification and restoration: it has demonstrated that primordial pluripotent stem cells can spontaneously enter the highly organized post-proenteral stage of development without exogenous genes or additional cell types. This not only helps to analyze the intrinsic development program of cells but also provides a standardized platform for disease modeling, mutation function verification, and regenerative medicine.

However, this model also has certain limitations: Due to the lack of support from extraembryonic tissues such as the placenta and yolk sac, its further development to later stages is restricted; Meanwhile, although the morphology and molecular markers of the model are close to those of natural embryos, whether their physiological functions are completely equivalent still needs further verification, and the stability and reproducibility of the model among different cell lines also need to be evaluated on a large scale.

These breakthroughs have continuously driven the in-depth exploration of pluripotent stem cell therapy in the field of regenerative medicine, highlighting its value in the treatment of refractory diseases and basic research in life sciences, and also injecting a continuous stream of impetus into the innovation and breakthroughs of future medical technologies.