Scientists at the Gladstone Institutes and the University of California, San Francisco (both CA, USA) have successfully reprogrammed human skin cells into fully functional, insulin-producing pancreatic cells that prevented the onset of diabetes in a mouse model of the disease in a method with potential for greater scale-up.
Scientists at the Gladstone Institutes and the University of California, San Francisco have successfully converted human skin cells into fully functional pancreatic cells in a cellular reprogramming method that has great potential for efficient scale-up, and therefore increases the potential for development of a personalized therapy for diabetes, whether through drug screening or cell therapy.
“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 Matthias Hebrok, PhD, director of the Diabetes Center at the University of California, San Francisco and a co-senior author on the study. “This finding opens up the opportunity for the analysis of patient-specific pancreatic beta cell properties and the optimization of cell therapy approaches.”
The team used pharmaceutical and genetic molecules to reprogram skin cells into endoderm progenitor cells — rather than a pluripotent stem cell state — then added molecules activating rapid endoderm cell division, allowing more than a trillion-fold expansion. No evidence of tumor formation was found and the cells maintained their identity.
Next, the scientists differentiated the cells into pancreatic precursor cells then into pancreatic beta cells, which produced insulin in response to changes in glucose levels and, upon transplantation into a mouse model of diabetes, prevented development diabetes in a mouse model of the disease.
“This study represents the first successful creation of human insulin-producing pancreatic beta cells using a direct cellular reprogramming method,” says first author Saiyong Zhu, PhD, a postdoctoral researcher at the Gladstone Institute of Cardiovascular Disease. “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.”
Sheng Ding, PhD, a senior investigator in the Roddenberry Stem Cell Center at Gladstone and co-senior author on the study, added: “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. 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.”
Source: https://gladstone.org/about-us/news/insulin-producing-pancreatic-cells-created-human-skin-cells; Zhu S, Russ HA, Wang X et al. Human pancreatic beta-like cells converted from fibroblasts. Nat. Commun. 7, 10080 (2016).