Cutting-edge cell therapy for diabetes care: a new era with exciting therapeutic achievements

Recent advances in medical research bring us closer to a world that manages type 1 diabetes without the need for continuous blood sugar monitoring or routine insulin injections. Scientists have been exploring innovative cellular therapies designed to restore the body’s ability to produce insulin naturally. These cutting-edge methods involve producing insulin-producing cells from stem cells, bringing new hope to millions of people with this chronic disease. These breakthrough journeys are full of fascinating discoveries and promising potential, which marks an important step forward in the fight against type 1 diabetes.

The study, led by Professor Rasoul Salehi, along with Dr. Sahar Sepyani, Dr. Sedigheh Momenzadeh, Dr. Reza Nedaeinia of Isfahan University, and Dr. Saied Safabakhsh of Microseian School of Disease Prevention and Research, is published in in Slas Discovery magazine.

The marker of type 1 diabetes is the autoimmune destruction of pancreatic beta cells, leading to chronic hyperglycemia levels and severe complications, even if it is not effectively treated. Traditional treatments revolve around exogenous insulin administration, which is full of challenges in maintaining stable glucose levels. The search for endogenous insulin production by replacing the insulin-producing cells has long been the holy grail, but the scarcity of suitable donors has hindered its widespread use.

Recent advances in stem cell research have opened up new avenues for the production of insulin-producing cells (IPCs). The researchers have developed protocols to derive 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 beta-cell-specific transcription factors is a direct strategy for IPC generation and provides a direct and effective method for the generation of these key cells.”

This study delves into the molecular mechanism of β-cell differentiation and highlights the key role of transcription factors. These factors regulate the development of pancreatic cells from progenitor cells to functional beta cells capable of producing insulin. For example, the transcription factors PDX1, NKX6.1 and NGN3 are essential for guiding stem cells through complex insulin-producing cells. As Professor Salehi pointed out, “Understanding the function and interaction of these transcription factors is key to advancing IPC generation technology.”

A major challenge is the repeatability of protocols that generate IPCs. The variability of differentiation efficiency of different stem cell lines highlights the need for refined and consistent approaches. The researchers’ innovative approach involves direct manipulation of beta-cell transcription factors, resulting in higher efficiency and shorter time scales of IPC production. This method bypasses the previously used laborious multi-step process, marking a significant improvement in the field.

In addition to traditional 2D culture systems, the study explores 3D culture techniques such as organoids and spheres that more accurately mimic the natural cellular environment of the pancreas. These 3D models show the maturity and functional improvement of IPC, providing a promising platform for future therapeutic applications. Another pioneering aspect of this study is the use of cell reprogramming, where non-beta cells are converted into insulin-producing cells by introducing specific transcription factors. This technology shows promise in various cell types, including pancreatic acinar cells and hepatocytes. Professor Salehi explained: “Transdifferentiation utilizes the inherent plasticity of cells, guiding them towards the fate of beta cells by activating key genes involved in insulin production.”

The encapsulation of beta cells to protect them from immune rejection while allowing nutrients and oxygen exchange, another innovative strategy highlighted in the study. Various materials and devices have been developed to create a supportive environment for transplanted cells, thereby enhancing their vitality and function. As Professor Salehi said, “encapsulation technology is critical to the long-term success of cell-based therapies, providing protective barriers that ensure the survival and efficacy of implanted cells.”

The work of the research team represents an important step in the fight against type 1 diabetes. Their findings not only enhance our understanding of beta cell development, but also pave the way for more effective and scalable cell-based therapies. The next phase of this study will focus on optimizing these techniques and conducting clinical trials to evaluate their efficacy in patients.

As Professor Salehi concluded: “The ultimate goal is to obtain a reliable and sustainable source of insulin-producing cells that can restore endogenous insulin production in patients with type 1 diabetes, thus providing better Quality of life and reduce dependence on exogenous insulin. Transparent

Journal Reference

Sahar Sepyani, Sedigheh Momenzadeh, Saied Safabakhsh, Reza Nedaeinia, Rasoul Salehi, “Administrative approach to cell-based cell-based approaches to ultimate success,” Slas Discovery, 2024. /J.Slasd. 2023.11.002

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