Obtaining iPSC is fundamentally faster and more efficient
Embryonic stem cells (ESCs) have an exceptionally high therapeutic potential, therefore, the developer of a method for obtaining induced pluripotent stem cells (iPSCs) with similar properties from adult skin cells Shinya Yamanaka was awarded the Nobel Prize in 2012. However, the effectiveness of this method is very low and the resulting cells are unsuitable for clinical use.
Researchers at the Weizmann Institute, working under the guidance of Dr. Yaqub Hanna, have proposed an approach that increases the efficiency of the iPSC production process from 1% (or less), provided by the most effective of the modern modifications of the method, to 100%. They managed to achieve this by releasing a molecular "brake" that prevents the transformation of adult differentiated cells into stem cells.
Left column: traditional method of producing induced pluripotent stem cells (iPSCs). Right column: A new method for obtaining iPSCs developed by Dr. Hanna's group. Above: skin cells (red); in the center: iPSCs obtained from skin cells (green); below: overlay of upper and central images. Skin cells successfully reprogrammed into iPSCs look bright yellow. Only a small part of the cells in the image on the left underwent reprogramming, unlike the result in the image on the right.In their work, the authors drew attention to the MBD3 protein, whose functions were still unknown.
Unlike the vast majority of proteins produced by certain cells at certain periods to perform certain functions, the MBD3 protein is expressed by all cells of the body at all stages of its development. A more detailed study revealed a small exception to this rule: It turned out that MBD3 is not expressed by dividing cells of the nascent embryo during the first three days after fertilization of the egg. On the fourth day after fertilization, the cells begin to synthesize the MBD3 protein, which coincides with the beginning of their differentiation and the gradual loss of pluripotency (the ability to differentiate into cells of different types).
To reprogram skin cells, Shinya Yamanaka inserted four genes into their genome using viral vectors, which made the resulting iPSCs potentially unsafe when administered to a patient. The whole process took four weeks, and the cell yield was only about 0.1%. The authors demonstrated that the removal of the MBD3 protein shortens the period of cell transformation to 8 days and increases the efficiency of the process by up to 100%. This discovery is of crucial importance for the development of iPSC production methods for clinical use, but the issue of ensuring the safety of the resulting cells remains open.
Dr. Hanna emphasizes that his group's achievement is based on observations of the natural mechanisms of embryonic development. He also notes that when working with cell reprogramming processes, researchers can greatly benefit from the most in-depth study of the processes of formation of embryonic stem cells in nature, since it is nature that produces the best cells using the most effective method.
Article by Yoach Rais et al. Deterministic direct reprogramming of somatic cells to pluripotency is published in the journal Nature.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Weizmann Institute of Science:
Stem Cell Reprogramming Made Easier.
20.09.2013