New Treatment for Diabetes By Reprogramming Cells

Susanna Sisson's picture
Diabetes treatment and human cell

Scientists at the Gladstone Institutes, and the University of California, San Francisco (UCSF) have succeeded in transforming human fibroblasts, a type of skin cell, into pancreatic cells via a process called direct cellular reprogramming, an accomplishment that brings personalized cell therapy one step closer for those who suffer from diabetes.

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Sheng Ding, PhD, a senior investigator at the Gladstone Institutes and stem cell researcher uses small molecule drug mixtures to initiate the differentiation of fibroblasts into a variety of other cell types. Dr. Ding’s use of chemical reprogramming skips some of the time-intensive steps involved in more traditional stem cell approaches.
After reprogramming the cells, the team of scientists transplanted the transformed cells, which behave like fully functioning pancreatic beta cells capable of producing insulin in response to changing levels of glucose, into mice. They found the cells not only produced insulin, but protected the mice from developing diabetes.

Their findings [1] were recently published in Nature Communications. The scientists appear to have made significant advancements over prior, more time consuming methods involving pluripotent stem cell methodology. The new simplified technique is more efficient and allows the manufacture of trillions of target cells. The improved technique and a relatively new “cocktail” of four small molecules which has been used in previous studies to regenerate heart [4], brain [5], and liver [6] cells made this successful study possible. Dr. Ding has also made advancements in cellular reprogramming and spinal cord regeneration.

“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.

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Opportunity for Personalized Diabetes Treatment

“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, director of the Diabetes Center at UCSF 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.” [3]

“This development ensures much greater regulation in the manufacturing process of new cells,” says Sheng Ding, PhD, a senior investigator in the Roddenberry Stem Cell Center at Gladstone and co-senior author on the study, “Now we can generate virtually unlimited numbers of patient-matched insulin-producing pancreatic cells.”
The use of autologous reprogrammed cells should equate to fewer complications for future patients.

“Eventually, patients with a broad array of diseases may be able to transform their own cells simply by taking a pill,” says Dr. Ding.

Resources:
1. Zhu, S. et al. Human pancreatic beta-like cells converted from fibroblasts. Nat. Commun. 7:10080 doi: 10.1038/ncomms10080 (2016).
2. http://www.nature.com/ncomms/2016/160106/ncomms10080/full/ncomms10080.html
3. https://gladstone.org/about-us/news/insulin-producing-pancreatic-cells-created-human-skin-cells
4. https://gladstone.org/about-us/press-releases/gladstone-scientists-develop-new-molecular-%E2%80%9Ccocktail%E2%80%9D-transform-skin-cells
5. https://gladstone.org/about-us/press-releases/gladstone-scientist-converts-human-skin-cells-functional-brain%C2%A0cells
6. https://gladstone.org/about-us/press-releases/scientists-transform-skin-cells-functioning-liver%C2%A0cells

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