Scientists have succeeded for the first time in directly reprogramming human blood cells into a previously unknown type of neural stem cell. These induced stem cells are similar to those that occur during the early embryonic development of the central nervous system. They can be modified and multiplied indefinitely in the culture dish and can represent an important basis for the development of regenerative therapies.
For the first time, the team has succeeded in reprogramming mature human cells in such a way that a defined type of induced neural stem cells is produced that can multiply almost indefinitely. "We used four genetic factors like Yamanaka, but different ones for our reprogramming," explains the first author of the study. "We assumed that our factors would allow reprogramming to an early stage of development of the nervous system."
In the past, other research groups also reprogrammed connective tissue cells into mature nerve cells or neural precursor cells. However, these artificially produced nerve cells often could not be expanded and could therefore hardly be used for therapeutic purposes. "Often, it was a heterogeneous mixture of different cell types that might not exist in the body under physiological conditions," said the senior author.
What is special about the reprogrammed cells is that they are a homogeneous cell type that resembles a stage of neural stem cells that occurs during the embryonic development of the nervous system. "Corresponding cells exist in mice and probably also in humans during early embryonic brain development," said the author. "We have described here a new neural stem cell type in the mammalian embryo.
These so called "induced Neural Plate Border Stem Cells" (iNBSCs) have a broad development potential. The iNBSCs are expandable and multipotent and can develop in two different directions. On the one hand, they can take the path of development to mature nerve cells and their supplier cells, the glial cells, i.e. become cells of the central nervous system. On the other hand, they can also develop into cells of the neural crest, from which different cell types emerge, for example peripheral sensitive nerve cells or cartilage and bones of the skull.
The iNBSCs thus form an ideal basis for generating a broad range of different cell types for an individual patient. "These cells have the same genetic material as the donor and are therefore presumably recognized as "self" by the immune system and are not rejected," explains the author.
The CRISPR/Cas9 gene scissors can be used to modify the iNBSC or repair genetic defects, as the scientists have shown in their experiments. "They are therefore of interesting both for basic research and the search for new active substances and for the development of regenerative therapies, for example in patients with diseases of the nervous system. However until we can use them in patients, a lot of research work will still be necessary," emphasizes the senior author.
https://www.dkfz.de/en/presse/pressemitteilungen/2018/dkfz-pm-18-71-Human-blood-cells-can-be-directly-reprogrammed-into-neural-stem-cells.php
https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(18)30551-4
