22 January 2019

Cell therapy of diabetes

Researchers searching for new effective methods of treating diabetes mellitus have long turned their attention to stem cells. These cells can be transformed into beta cells that produce insulin, a hormone that regulates blood glucose levels. However, there is one serious obstacle: the amount of insulin they produce is very difficult to regulate.

Researchers at Washington University School of Medicine in St. Louis, working under the guidance of Associate Professor Jeffrey R. Millman, have developed a new method of cell reprogramming that provides beta cells that respond quickly and adequately to fluctuations in blood glucose levels.

Millman was part of a group of Harvard University researchers who in 2014 turned skin cells into stem cells, and in 2016 performed the same procedure with skin cells of a patient with diabetes mellitus. In each case, the resulting stem cells were affected by various growth factors to transform them into insulin-producing beta cells. However, such beta cells did not function as well as scientists had hoped. They produced either too much insulin or nothing at all.

To obtain a new type of beta cells, the authors made many changes to the reprogramming protocol, which provided a higher sensitivity of new cells, as well as their ability to secrete insulin in amounts corresponding to changes in glucose levels.

Rice. Beta cells derived from pluripotent stem cells are stained with a red dye when they begin to synthesize insulin in response to glucose exposure.

These beta cells were transplanted into immunosuppressive mice with simulated diabetes mellitus. After a few days, they began to produce insulin in an amount sufficient to effectively regulate the level of glucose in the blood of animals. This provided a functional cure for diabetes mellitus for several months, which for most of the animals involved roughly corresponded to their life expectancy.

Millman notes that he cannot predict when such cells will be ready for clinical trials. He notes that there are at least two possible options for their clinical application. Firstly, the cells can be encapsulated in a gel-like material, the diameter of the pores of which will simultaneously ensure the release of insulin and prevent the penetration of immune cells into the implant. Another promising option is the use of genetic modification that will make beta cells invisible to the immune system after implantation.

The authors believe that after confirming the safety and effectiveness of the approach in clinical trials, the beta cell production method they developed can be quickly scaled up for mass use. In their laboratory, they manage to grow more than a billion beta cells in just a few weeks.

Article by Velazco-Cruz L et al. The acquisition of dynamic function in human stem cell-derived beta cells is published in the journal Stem Cell Reports.

Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Washington University School of Medicine in St. Louis: New hope for stem cell approach to treating diabetes.

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