A team of scientists led by Juan Carlos Izpisua, director of the Gene Expression Laboratory of the Salk Institute of the USA and Extraordinary Professor of Developmental Biology at UCAM, has developed a method, “with unprecedented efficiency”, which allows obtaining cells pancreatic beta cells suitable for autotransplantation from human iPS cells, according to the educational institution.
Diabetes is a chronic disease that occurs when the pancreas does not produce enough insulin (type I diabetes) or when the body does not use the insulin it produces effectively (type II diabetes). The effect it causes is hyperglycemia (increased glucose in the blood), which over time seriously damages organs and systems such as the heart, blood vessels, eyes, kidneys or nerves. Currently, more than 400 million people suffer from this disease worldwide.
The method has shown “unprecedented efficacy”, starting from human iPS cells
Through this project, promoted and funded by UCAM with the collaboration of the Primafrío Foundation, the team of researchers led by Izpisua Belmonte has managed to manufacture functional pancreatic beta cells from induced pluripotent human cells (from adult cells). The protocol designed for this has shown “unprecedented” efficiency starting from adult cells. “This discovery represents another step towards a better understanding of the disease and its possible treatment,” says Izpisua, principal investigator of the project. ‘In vitro and in vivo tests showed that the pancreatic beta cells thus obtained are physiologically functional, that is, they detect glucose and reverse hyperglycemia in experimental diabetic models in the laboratory. Furthermore, these cells, once transplanted, are safe and did not form teratomas in the long term, ”says Haisong Liu, first author of the work.
Although important efforts have been made in the last decade to achieve the differentiation of human iPS cells into pancreatic beta cells, the clinical application of these methodologies has been hampered for different reasons: the designed protocols had low efficiency; the beta cells obtained were very heterogeneous, a high percentage of them lacked the desired functionality and presented a risk of teratoma formation; and the protocols used depended, to a great extent, on the starting cell line, presenting a limited value to generate specific beta cells for each patient. “All these problems could be due to the lack of knowledge, until now, of how to regulate the signals involved in the transformation of human iPS cells into beta cells of the pancreas,” says Llanos Martínez, professor at UCAM and co-author of the project.
In experimental laboratory models, hyperglycemia was reversed
However, in this project, the results of which are published in the journal ‘Nature Communications’, “we made a systematic selection of chemicals and proteins to be used in each step of the conversion of human iPS cells into beta cells of the pancreas, for which we a new protocol ”, points out Estrella Núñez, vice-rector for Research at UCAM.
The designed method is precise and highly efficient to generate pancreatic progenitors from human iPS cells and efficiently group them into three-dimensional structures.