Functioning human pancreatic cells after they’ve been transplanted into a mouse are shown. Credit: Saiyong Zhu
When transplanted into mice, the cells protected them from developing diabetes in a mouse model of the disease by producing insulin in response to changes in glucose levels. The new study also presents significant advancements in cellular reprogramming technology, which will allow scientists to efficiently scale up pancreatic cell production and manufacture trillions of the target cells in a step-wise, controlled manner. This accomplishment opens the door for disease modeling and drug screening and brings personalized cell therapy a step closer.
“Our results demonstrate for the first time that human adult skin cells can be used to efficiently and rapidly generate functional pancreatic cells that behave similar to human beta cells,” says Matthias Hebrok, PhD. “This finding opens up the opportunity for the analysis of patient-specific pancreatic beta cell properties and the optimization of cell therapy approaches.”
In the study, the scientists first used pharmaceutical and genetic molecules to reprogram skin cells into endoderm progenitor cells -early developmental cells that have already been designated to mature into one of a number of different types of organs. With this method, the cells don’t have to be taken all the way back to a pluripotent stem cell state, so they can turn them into pancreatic cells faster. The researchers have used a similar procedure previously to create heart, brain, and liver cells.
After another 4 molecules were added, the endoderm cells divided rapidly, allowing more than a trillion-fold expansion. Critically, the cells did not display tumor formation, and they maintained their identity as early organ-specific cells. They then progressed these endoderm cells two more steps, first into pancreatic precursor cells, and then into fully-functional pancreatic beta cells. “The final step was the most unique–and the most difficult–as molecules had not previously been identified that could take reprogrammed cells the final step to functional pancreatic cells in a dish,” said Saiyong Zhu, PhD.
“This new cellular reprogramming and expansion paradigm is more sustainable and scalable than previous methods. Using this approach, cell production can be massively increased while maintaining quality control at multiple steps….Now we can generate virtually unlimited numbers of patient-matched insulin-producing pancreatic cells,” said Sheng Ding, PhD. https://gladstone.org/about-us/press-releases/insulin-producing-pancreatic-cells-created-human-skin-cells
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