Opening up new possibilities of treating diabetes and substitutes for animal testing

The joint research team of late Prof. Sang-Hoon Lee and Prof. Seok Chung at Korea University and 

Prof. Maike Sander at the U.S.’ Pediatric Diabetes Research Center

published their findings in Science Advances.

The research results are expected to be applied to multidisciplinary research and various biomedical areas for diabetes treatment.

A joint research team composed of researchers from Korea University, the U.S.’ Pediatric Diabetes Research Center, and the venture company Next&Bio developed functional pancreatic islet spheroids mimicking in vivo physiology and engineered three-dimensional (3D) islet architecture to enable long-term in vitro culture of pancreatic islet spheroids. Their research findings were published in Science Advances (IF: 12.804), an open access journal from AAAS, the publisher of Science. The research team consisted of late Prof. Sang-Hoon Lee (School of Biomedical Engineering of Korea University and KU-KIST Graduate School of Converging Science and Technology) and Prof. Seok Chung (School of Mechanical Engineering of Korea University and KU-KIST Graduate School of Converging Science and Technology); Prof. Maike Sander (U.S.’ Pediatric Diabetes Research Center); Dr. Yesl Jun; and researchers (Next&Bio).

* Title of the paper: In vivo–mimicking microfluidic perfusion culture of pancreatic islet spheroids

The pancreatic islets, also known as the islets of Langerhans, are three-dimensional clusters of approximately 1,000 cells located within the pancreas that are responsible for the production and release of hormones that regulate glucose levels and the in vivo release of insulin. When the pancreatic islets no longer make insulin, you may develop diabetes, which is one of the most common chronic diseases in the world, affecting approximately 350 million people worldwide. People with diabetes suffer from various life-long disadvantages such as daily blood glucose testing and monitoring, insulin injections, insulin shock, and complications.

Research on the cause, development and treatment of diseases directly related to the pancreas, including diabetes, is ongoing, but only with cells cultured on petri dishes or with animal testing models, so drugs or therapies cannot be accurately analyzed and the cause of such diseases cannot be identified. Moreover, given the growing anti-animal testing movement, there is also increasing demand for a new substitute system for verifying the efficacy of drugs or therapies.

Under the leadership of the first author Dr. Yesl Jun, the research team utilized three-dimensional (3D) cell culture and microfluidic techniques, thus developing a new three-dimensional cell culture platform to create a microfluidic environment that mimics in vivo attributes. The platform enables verification of the efficacy of diabetic drugs or therapies without animal testing and proves the possibility of treating diabetes through the transplantation of pancreatic cells. This is important because if the pancreas does not function properly, people may develop diabetes, one of the most common diseases in the world, and those afflicted suffer from various disadvantages every day, including blood testing and insulin injections. Nevertheless, there is currently no particular treatment or drug for the disease. However, the newly developed technique of the research team supports the large scale even culturing of pancreatic cells. When tolbutamide, a diabetic drug, and rapamycin, an immunosuppressant in islet transplantation, were used, they stimulated insulin secretion and toxicity resistance by the cultured cells. This implies that the research results can be applied to drug evaluation, attesting to the commercial viability of the technique. The research team also confirmed that when evenly incubated pancreatic cells were fed into alginate fibers and transplanted into diabetic mice, the mice were relieved without drug injections and their survival period prolonged substantially.

Prof. Seok Chung said, “This research is significant as it is the first research that discovered that a certain microfluidic environment in vitro supports a long-term pancreatic cell culture,” adding, “We proved that the environment can relieve diabetic symptoms with mice. We expect that this will contribute to new advances in the research of the pancreas and pancreatic islets. We also believe that our research findings will enhance our understanding of the β cells in the pancreatic islets of Langerhans and be applied to various biomedical areas, such as transplantation of pancreatic islets and diabetic stem cells.”

Dr. Yesl Jun, whose supervisor was late Prof. Sang-Hoon Lee, said, “Prof. Lee would have been very pleased to see the findings of this research. He was a passionate researcher and teacher.”

This research was supported by the Basic Science Research Program through the National Research Foundation (NRF) of Korea and the Technology Innovation Program funded by the Ministry of Trade, Industry and Energy (MOTIE) of Korea.

Figure 1. 3D islet models in a microfluidic chip using reaggregated islet spheroids and concave microwell arrays integrated with an osmotic micropump. The osmotic micropump controls the flow conditions of the chip and mimics the in vivo microenvironment in the islet, thus maintaining the in vivo physiological features of the pancreatic islets.

Figure 2. Replication of in vivo microenvironment and drug testing results. (A) Differences in cell-cell response and insulin secreted from islet spheroids under different culture conditions; (B) Inner structures of spheroids formed under different culture conditions; and (C) Cell viability in islet spheroids under different culture conditions