Functioning human pancreatic cells after they've been transplanted into a mouse. [Saiyong Zhu]
Functioning human pancreatic cells after they’ve been transplanted into a mouse. [Saiyong Zhu]

Personalized medicine has recently taken a step forward for patients suffering from diabetes. In a new study, scientists at the Gladstone Institutes and the University of California, San Francisco (UCSF) have successfully converted human skin cells into fully functional pancreatic cells. These new cells were able to produce insulin in response to changing glucose levels. Moreover, when transplanted into mice, the pancreatic cells protected the animals from developing diabetes.

The investigators described how their cellular reprogramming technology allowed them to efficiently scale up pancreatic cell production, an advance that could lead to the manufacture of trillions of the target cells in a step-wise, controlled manner. Such production capabilities could provide considerable assistance to patients and open up new avenues for disease modeling and drug screening.   

“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,” explained co-senior study author Matthias Hebrok, Ph.D., director of the Diabetes Center at UCSF. “This finding opens up the opportunity for the analysis of patient-specific pancreatic beta cell properties and the optimization of cell therapy approaches.”

The results of this study were published recently in Nature Communications through an article entitled “Human pancreatic beta-like cells converted from fibroblasts.”

The research team was able to first reprogram skin cells into endoderm progenitor cells by exposing them to an array of pharmaceutical and genetic compounds. The advantage of this technique is that the cells don't have to be taken all the way back to a pluripotent stem cell state, meaning the scientists can turn them into pancreatic cells faster—a procedure the researchers have used previously to create heart, brain, and liver cells.

The scientists were then able to persuade the endoderm cells to rapidly proliferate while carefully monitoring them to make certain that they did not display any evidence of tumor formation. Finally, the researchers pushed the cells forward, first into pancreatic precursor cells, and then into fully functional pancreatic beta cells. Critically, these cells protected the mice from developing diabetes in a model of disease, having the essential ability to produce insulin in response to changes in glucose levels.   

“This study represents the first successful creation of human insulin-producing pancreatic beta cells using a direct cellular reprogramming method,” noted lead author Saiyong Zhu, Ph.D., a postdoctoral researcher at the Gladstone Institute of Cardiovascular Disease. “The final step was the most distinctive—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.”

The investigators were excited by their findings and are looking forward to continuing their research by expanding to various other animal models of diabetes.  

“This new cellular reprogramming and expansion paradigm is more sustainable and scalable than previous methods,” remarked co-senior study author Sheng Ding, Ph.D., a senior investigator at the Roddenberry Stem Cell Center at Gladstone. “Using this approach, cell production can be massively increased while maintaining quality control at multiple steps. This development ensures much greater regulation in the manufacturing process of new cells. Now we can generate virtually unlimited numbers of patient-matched, insulin-producing pancreatic cells.”








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