06 December 2012

Indirect conversion is a new method of cell reprogramming

There are two fundamentally different approaches to obtaining stem cells for research and clinical purposes: isolation of initially immature embryonic stem cells or reprogramming of somatic cells into so-called induced pluripotent stem cells capable of forming various types of adult body tissues.

The practical application of embryonic cells raises a number of ethical issues. In addition, cells and tissues grown from them in the recipient's body can trigger immune reactions, and the remaining undifferentiated embryonic cells are capable of forming teratoma tumors consisting of differentiated cells of many types. In turn, induced pluripotent stem cells also have their drawbacks: large time costs for their production and the same danger of teratoma formation.

In search of a solution to this problem, scientists have developed a method called "direct conversion between directions of differentiation" – ILC, from the English "direct lineage conversion". Unlike traditional methods that provide the production of pluripotent stem cells capable of dividing and differentiating into cells of different types, the direct conversion method involves the transformation of a somatic cell into a cell of another type. For example, one skin cell can turn into only one mature muscle cell.

American researchers from the Salk Institute of Biological Sciences have devoted their work to further improving this approach. As a result, they developed a technology of so-called indirect conversion between the directions of differentiation, the essence of which is the transformation of a somatic cell of one tissue, with short-term exposure to reprogramming factors, into one partially differentiated precursor cell of another tissue.

This method not only reduces the risk of developing teratomas, since it does not involve the return of cells to an unstable pluripotent state, but also reduces the time spent on obtaining cells of the desired differentiation line from almost two months to 15 days.

With the help of a new approach, researchers were able to transform adult skin fibroblasts into angioblasts – progenitor cells that form blood and lymphatic vessels.

The resulting cells are able to divide and differentiate into cells of the endothelium and vascular smooth muscles. When implanted in mice, they integrate into the tissues of the existing vascular network.

Endothelial cells obtained using the method of indirect conversion between the directions of differentiation from human fibroblasts.
Cell nuclei are colored blue, endothelial cell marker proteins are green and red.

According to the head of the study Juan Belmonte (Juan Carlos Izpisua Belmonte), one of the ideas for the long term is the use of cells obtained with the help of new technology to create three-dimensional structures capable of integration into the tissues of the body.

Article by Leo Kurian et al. Conversion of human fibroblasts to angioblast-like progenitor cell is published in the journal Nature Methods.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Salk Institute for Biological Studies:
Salk scientists develop faster, safer method for producing stem cells.


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