Recent advancements in medical research are bringing us closer to a world where managing Type 1 Diabetes doesn’t require constant blood sugar monitoring or regular insulin injections. Scientists have been exploring innovative cell-based therapies that aim to restore the body’s ability to produce insulin naturally. These cutting-edge approaches involve generating insulin-producing cells from stem cells, offering new hope for millions of people living with this chronic condition. The journey toward these breakthroughs is filled with fascinating discoveries and promising potential, marking a significant step forward in the fight against Type 1 Diabetes.

The research, led by Professor Rasoul Salehi, along with Sahar Sepyani, Dr. Sedigheh Momenzadeh, and Dr. Reza Nedaeinia from Isfahan University, and Dr. Saied Safabakhsh from the Micronesian Institute for Disease Prevention and Research, was published in the journal SLAS Discovery.

Type 1 Diabetes is marked by the autoimmune destruction of pancreatic β-cells, leading to chronic high blood sugar levels and severe complications if not managed effectively. Traditional treatment revolves around exogenous insulin administration, a method fraught with challenges in maintaining stable glucose levels. The quest for endogenous insulin production by replacing insulin-producing cells has long been the holy grail, yet the scarcity of suitable donors has impeded its widespread application.

Recent strides in stem cell research have opened new avenues for generating insulin-producing cells (IPCs). Researchers have developed protocols for deriving IPCs from various stem cell types, including human pluripotent stem cells (hPSCs) such as embryonic stem cells (ES) and induced pluripotent stem cells (iPSCs). Professor Salehi emphasized, “The utilization of β-cell-specific transcription factors stands out as a direct strategy for IPC generation, offering a straightforward and efficient method for producing these critical cells.”

The research delved into the molecular mechanisms underlying β-cell differentiation, highlighting the pivotal role of transcription factors. These factors regulate the development of pancreatic cells from progenitors to fully functional β-cells capable of insulin production. For instance, the transcription factors PDX1, NKX6.1, and NGN3 are crucial in guiding stem cells through the complex process of becoming insulin-producing cells. As Professor Salehi noted, “Understanding the function and interplay of these transcription factors is key to advancing IPC generation techniques.”

One significant challenge has been the reproducibility of protocols for generating IPCs. The variability in differentiation efficiency across different stem cell lines underscores the need for refined and consistent methods. The researchers’ innovative approach involved direct manipulation of β-cell transcription factors, resulting in higher efficiency and shorter timescales for IPC production. This method bypasses the laborious multi-step processes previously employed, marking a significant improvement in the field.

In addition to traditional 2D culture systems, the research also explored 3D culture techniques such as organoids and spheroids, which more accurately mimic the natural cellular environment of the pancreas. These 3D models have shown improved maturation and functionality of IPCs, offering a promising platform for future therapeutic applications. Another groundbreaking aspect of this research is the use of cell reprogramming, where non-β cells are converted into insulin-producing cells by introducing specific transcription factors. This technique has shown promise in various cell types, including pancreatic acinar cells and liver cells. Professor Salehi explained, “Transdifferentiation leverages the inherent plasticity of cells, guiding them towards a β-cell fate by activating key genes involved in insulin production.”

The encapsulation of β-cells to protect them from immune rejection while allowing nutrient and oxygen exchange is another innovative strategy highlighted in the research. Various materials and devices have been developed to create a supportive environment for transplanted cells, enhancing their viability and functionality. As Professor Salehi stated, “Encapsulation technology is pivotal for the long-term success of cell-based therapies, providing a protective barrier that ensures the survival and efficacy of the implanted cells.”

The research team’s work represents a significant step forward in the fight against Type 1 Diabetes. Their findings not only enhance our understanding of β-cell development but also pave the way for more effective and scalable cell-based therapies. The next phase of this research will focus on optimizing these techniques and conducting clinical trials to assess their efficacy in patients.

As Professor Salehi concluded, “The ultimate goal is to achieve a reliable and sustainable source of insulin-producing cells that can restore endogenous insulin production in patients with Type 1 Diabetes, offering them a better quality of life and reducing their dependence on exogenous insulin.”

Journal Reference

Sahar Sepyani, Sedigheh Momenzadeh, Saied Safabakhsh, Reza Nedaeinia, Rasoul Salehi, “Therapeutic approaches for Type 1 Diabetes: Promising cell-based approaches to achieve ultimate success,” SLAS Discovery, 2024.  DOI:

About the Author

Rasoul Salehi, (PhD) distinguished professor of Molecular Biology and Chief, Department of Genetics and Molecular Biology in addition to being the Director of Pediatric Inherited Diseases Research Center at Isfahan University of Medical Sciences, Isfahan, Iran. Professor Salehi, during the past 30 years of his scientific and academic activities, has graduated many Ph.D. students. He has made significant contributions in advancement of science through numerous scientific publications.