Reprogrammed cells will help with diabetes
The death of insulin-producing beta cells of the pancreas is the cause of the development of type 1 diabetes mellitus or occurs in the pronounced stages of type 2 diabetes. Theoretically, transplantation of healthy beta cells should stop the development of the disease, but scientists have not been able to develop an effective method of growing these cells in the laboratory from either embryonic or induced pluripotent stem cells.
Researchers at the University of Pennsylvania, working under the guidance of Professor Klaus H. Kaestner, have proposed a fundamentally new approach to solving this problem. They obtained functional beta cells by reprogramming alpha cells that make up 15-20% of pancreatic Langerhans islet cells. The function of alpha cells is to synthesize and release glucagon, a peptide hormone that increases blood glucose levels.
The study of gene methylation of pancreatic alpha cells showed that histone proteins associated with many genes in these cells simultaneously carry activating and suppressing activity modifications. Many of these genes are involved in the functioning of insulin-producing beta cells.
According to Kestner, it turned out that alpha cells to a certain extent are in a "plastic" epigenetic state. The authors suggested that this feature can be used to reprogram them into beta cells.
Indeed, treatment of the endocrine islets of the human pancreas with an Adox methyltransferase inhibitor led to the fact that many alpha cells (red) began to express a marker of beta cells - transcription factor PDX1 (white) - see Figure.
The fact of partial reprogramming of alpha cells into beta cells was confirmed by the fact that they began to produce a certain amount of insulin.
According to the authors, if such a transformation can be carried out in the conditions of the body, this situation will be a win-win for patients with diabetes mellitus, since it will simultaneously ensure the synthesis of insulin and a decrease in the level of glucagon, the level of which is usually increased in type 2 diabetes.
Article by Nuria C. Bramswig et al. Epigenomic plasticity enables human pancreatic alfa to beta cell reprogramming published in the Journal of Clinical Investigation.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of UPenn: Reprogramming Cells to Fight Diabetes.
25.02.2013