Scientists from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and the stem cell institute HI-STEM in Heidelberg for the first time successfully reprogrammed human blood cells into a previously unknown type of neural stem cells.
The resulting induced pluripotent stem cells are similar to those appearing during the early embryonic development of the central nervous system. Their reproduction and modification in the laboratory can be an important stage in the development of regenerative medicine.
Pluripotent stem cells are universal. They, in contrast to adult stem cells, can form all known types of body tissues. In 2006, the Japanese scientist Shinya Yamanaka demonstrated that such cells can be created in the laboratory from specialized mature cells.
For their production and reversal of development processes, only four genetic factors are sufficient. For the discovery of induced pluripotent stem cells (iPSCs), which have properties identical to embryonic stem cells, Yamanka was awarded the Nobel Prize in Medicine in 2012.
“This was a major breakthrough for stem cell research”, – said Andreas Trumpp, German Cancer Research Center (DKFZ) and Director of HI-STEM in Heidelberg. “This applies in particular to for research in Germany, where the generation of human embryonic stem cells is not permitted.
Stem cells have enormous potential both for basic research and for the development of regenerative therapies that aim to restore diseased tissue in patients. However, reprogramming is also associated with problems: For example, pluripotent cells can form germ line tumors, so-called teratomas”.
There is another way – to reverse the development of mature cells not fully. The Trumpp’s team for the first time has managed to successfully reprogram mature human cells in such a way that a defined type of induced neural stem cells is produced that can divide almost infinitely. The results of their work were published on December 20, 2018 in Cell Stem Cell.
“We used four genetic factors like Yamanaka, but different ones for our reprogramming”, – explains Marc Christian Thier, first author of the study. “We assumed that our factors would allow reprogramming to an early stage of development of the nervous system.”
Other research groups have also reprogrammed connective tissue cells into mature nerve cells or neural precursor cells. However, these artificially created neurons often could not be expanded, therefore they could 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”, – Andreas Trumpp explaining the problems.
Together with stem cell researcher Frank Edenhofer from the University of Innsbruck and neuroscientist Hannah Monyer from DKFZ and the Heidelberg University Hospital, Trumpp and his team have succeeded in reprogramming different human cells: connective tissue of the skin, pancreas as well as peripheral blood.
“The origin of the cells had no influence on the properties of the stem cells”, – said Thiers. “The possibility of extracting neural stem cells from the blood of patients without invasive intervention is a decisive advantage for future therapeutic approaches. “
The main feature of reprogrammed cells, obtained by specialists from Heidelberg, is that they form a homogeneous population, resembling a stage of nerve 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 Thier. “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 varied potential for development. The iNBSC is multipotent, multiplies well and can develop in two directions.
On the one hand, their differentiation can be directed to the formation of mature neurons and their supplier cells, the glial cells, i.e. the creation of cells of the central nervous system.
On the other hand, they can also develop into cells of the neural crest, from which various cell types are derived, for example, sensitive cells of the peripheral nervous system, as well as cartilage and the bones of the skull.
Thus, iNBSCs create the ideal basis for creating different types of cells individually for each 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 Thier.