In what can be said to be a significant achievement, the researchers at the Gladstone Institutes and the University of California, San Francisco (UCSF) have successfully converted human skin cells into fully-functional pancreatic cells. In response to changes in glucose levels, the new cells produced insulin. Also, when the cells were transplanted in a mouse model of the disease, they protected the animals from developing diabetes. The details of the study were published recently in the journal Nature Communications.
The results of the study are very encouraging as it shows the significant advancements in cellular reprogramming technology, which will enable scientists to efficiently scale up pancreatic cell production and manufacture trillions of the target cells in a step-wise, controlled manner. The researchers are very positive that this milestone will open avenues for disease modeling and drug screening and bring personalized cell therapy a step closer for patients living with diabetes.
Matthias Hebrok, PhD, director of the Diabetes Center at UCSF and a co-senior author on the study remarked that the results of their study 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. He added that this finding open up the opportunity for the analysis of patient-specific pancreatic beta cell properties and the optimization of cell therapy approaches.
Pharmaceutical and genetic molecules were used by the scientists to reprogram skin cells into endoderm progenitor cells. Such cells are early developmental cells that are designated to mature into one of a number of different types of organs. When following this method, the cells don’t have to be taken all the way back to a pluripotent stem cell state, which helps the scientists to turn them into pancreatic cells faster. Similar procedure has been used by the researchers previously to create heart, brain, and liver cells. Once another four molecules were added, the endoderm cells divided rapidly, allowing more than a trillion-fold expansion. The most important thing is that the cells did not display any evidence of tumor formation. They maintained their identity as early organ-specific cells after expansion.
These endoderm cells were then made to progress two more steps – the first step was to transform them into pancreatic precursor cells, and secondly into pancreatic beta cells that are fully-functional. The most significant aspect of these cells was that it protected the mice from developing diabetes in a model of disease. The cells were capable of doing so as they had the critical ability to produce insulin in response to changes in glucose levels.
Saiyong Zhu, PhD, a postdoctoral researcher at the Gladstone Institute of Cardiovascular Disease and the first author of the study opined that their study represents the first successful creation of human insulin-producing pancreatic beta cells using a direct cellular reprogramming method. He added that the final step in the process was the most unique as well as the most difficult because the molecules had not previously been identified that could take reprogrammed cells through the final step in creating functional pancreatic cells in a dish.
This innovative cellular reprogramming and expansion paradigm is by large more sustainable and scalable than previous methods added Sheng Ding, PhD, a senior investigator in the Roddenberry Stem Cell Center at Gladstone and co-senior author on the study. What sets this approach apart from others is the fact that cell production can be significantly increased without compromising the quality control. Since, there are quality checks at various levels; it ensures much greater quality regulation in the manufacturing process of new cells. Thanks to this process, it has enabled us to generate virtually unlimited numbers of patient-matched insulin-producing pancreatic cells.