Scientists at the German Cancer Research Center (DKFZ) and the HI-STEM * stem cell institute in Heidelberg have been able to reprogram human blood cells directly 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.
Stem cells are considered the most versatile of our tissues: they can multiply indefinitely and then – if they are pluripotent embryonic stem cells – generate all conceivable cell types. In 2006, Japanese scientist Shinya Yamanaka acknowledged that these cells could also be produced in the laboratory – from mature body cells. Only four genetic factors are sufficient to reverse the course of development and produce the so-called induced pluripotent stem cells (iPS) that have properties similar to embryonic stem cells. Yamanaka received the Nobel Prize for Medicine in 2012 for this discovery.
"This was a major breakthrough for stem cell research," said Andreas Trumpp of the German Cancer Research Center (DKFZ) and director of HI-STEM in Heidelberg. "This is especially true for research in Germany where the generation of human embryonic stem cells is not allowed. Stem cells have enormous potential for both basic research and the development of regenerative therapies aimed at restoring diseased tissue to patients. However, reprogramming is also associated with problems: for example, pluripotent cells can form tumors of the germ line, teratomas.
Another possibility is not to completely reverse the course of development. For the first time, the Trumpp team was able to reprogram mature human cells in such a way that a defined type of induced neural stem cells is produced and can multiply almost indefinitely. "We used four genetic factors like Yamanaka, but different for our reprogramming," explains Marc Christian Thier, the study's first author. "We assumed that our factors would allow reprogramming to an early stage of development of the nervous system."
In the past, other research groups have 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 hardly be used for therapeutic purposes. "It was often a heterogeneous mixture of different types of cells that may not exist in the body under physiological conditions," said Andreas Trumpp, explaining the problems.
Together with stem cell researcher Frank Edenhofer of the University of Innsbruck and neuroscientist Hannah Monyer of DKFZ and University Hospital of Heidelberg, Trumpp and his team were able to reprogram different human cells: connective tissue cells of the skin or pancreas, as well as peripheral blood cells. "The origin of the cells had no influence on the properties of stem cells," Thier said. In particular, the possibility of extracting neural stem cells from the blood of patients without invasive intervention is a decisive advantage for future therapeutic approaches.
What is special about the reprogrammed cells of the Heidelberg researchers is that they are a type of homogeneous cell 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 the embryonic development of the brain," Thier said. "We have described here a new type of neural stem cell in the mammalian embryo.
These so-called "induced neural plate frontier stem cells" (iNBSCs) have broad development potential. The iNBSCs of Heidelberg scientists 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 cells supplying glial cells, that is, cells of the central nervous system. On the other hand, they may also develop into neural crest cells from which different types of cells arise, for example peripheral sensitive nerve cells or cartilage and skull bones.
INBSCs thus form an ideal basis for generating a wide range of different cell types for an individual patient. "These cells have the same genetic material as the donor and therefore are presumably recognized as & # 39; own & # 39; by the immune system and are not rejected, "Thier explains.
The CRISPR / Cas9 gene shears can be used to modify iNBSC or repair genetic defects, as scientists have shown in their experiments. "They are therefore interesting both for basic research and for 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, much research work will still be needed, "emphasizes Trumpp.