Beta cells from fat deposits

Researchers at the Basel branch of the Swiss Higher Technical School of Zurich, working under the guidance of Professor Martin Fussenegger, managed to transform adipose tissue stem cells into cells almost identical to insulin-producing beta cells of the pancreas using an artificial genetic program. This is a great achievement on the way to the development of personalized diabetes therapy.

As part of the study, the authors obtained induced pluripotent stem cells (iPSCs) from adipose tissue cells of a 50-year-old patient, reprogrammed them with the help of growth factors into progenitor cells of insulin-producing cells, which were subsequently modified using a complex gene system designed so that the growth factors produced by its components accurately reproduced the process of maturation of beta-cells in the body.

The main growth factors involved in this process are proteins known as Ngn3, Pdx1 and MafA. Their concentrations change during the maturation process of beta cells. For example, MafA is absent at the beginning of the process and appears only on the fourth day, when the final maturation of cells occurs, while its concentration increases sharply, after which it remains at a high level. Changes in the concentrations of proteins Ngn3 and Pdx1 are very complex. While the concentration of Ngn3 increases and then decreases again, the level of Pdx1 increases at the beginning and closer to the end of the maturation process. Fussenegger emphasizes that in order to obtain functioning beta cells, these processes, including the temporal dynamics of changes in the concentrations of growth factors and their quantitative values, must be reproduced as accurately as possible.

Dynamics of changes in concentrations of the most important growth factors for beta cell differentiation.
Figure ETH Zurich.

Beta cells obtained as a result of differentiation of adipose tissue stem cells do not differ in appearance from their natural counterparts. One of the main features is the dark granules contained in them, which are stores of insulin. In the presence of glucose, these cells, as befits beta cells, begin to secrete insulin.

Comparison of conventional (left) and artificial beta cells (right).
A snapshot from an article in Nature Communications.

Despite the fact that the amount of insulin released by them is slightly lower than the values typical for ordinary cells, the researchers are pleased with the result, since they were able to reproduce the entire process of cell differentiation using genetic methods for the first time.

They note that earlier scientists directed and regulated the processes of cell differentiation by adding various chemical compounds and proteins to the culture medium using pipettes. However, the exact observance of concentration and time intervals at the same time is a very difficult task, and increasing the volume of cell production is almost impossible. The approach proposed by the authors is devoid of these disadvantages and ensures the transformation of 75% of adipose tissue stem cells into functional beta cells.

To date, the authors have only learned how to grow the beta cells they received in culture and have not attempted to test their ability to correct the manifestations of diabetes mellitus. In the near future, they plan to improve their method in such a way that the entire process of stem cell differentiation from beginning to end is carried out using genetic reprogramming.

Fussenegger is also confident that the approach proposed by his group can be used for the production of other types of cells. He notes that adipose tissue stem cells can be differentiated into cells of different types and most people have fat reserves from which these cells can be isolated if necessary.

Article by Pratik Saxena et al. A programmable synthetic lineage-control network that differentiates human iPSCs into glucose-sensitive insulin-secreting beta-like cells is published in the journal Nature Communications.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of ETH Zurich: Beta cells from love handles.

12.04.2016