Researchers from the German Malignancy Research Center (DKFZ) and the stem cell company HI-STEM* in Heidelberg have succeeded for the first time in directly reprogramming human blood cells into a previously unknown kind of neural stem cell. These types of induced stem cells resemble those that occur during the early embryonic development of the main anxious system. They can be modified and multiplied indefinitely in the culture meal and can represent an important basis for the development of regenerative treatments.
Stem cells are considered to be the all-rounders of our tissues: they can increase indefinitely and then — if they are pluripotent embryonic stem cells — generate all conceivable cellular types. In 2006, the Japanese scientist Shinya Yamanaka recognized that such tissues could also be produced in the laboratory — from mature body cells. 4 genetic factors alone are sufficient to reverse the course of development and produce so-called induced pluripotent originate cells (iPS) which have similar properties to embryonic originate cells. Yamanaka was granted the Nobel Prize for Medicine in 2012 for this discovery.
“This was a major breakthrough for stem cell research, inch said Andreas Trumpp, German born Cancer Research Center (DKFZ) and Director of HI-STEM in Heidelberg. “This is applicable in particular to for research in Germany, where the generation of human being embryonic stem cells is not permitted. Stem tissues have enormous potential both for basic research as well as for the development of regenerative therapies that aim to restore diseased tissue in patients. However, reprogramming is also associated with problems: For example, pluripotent tissues can form germ range tumors, so-called teratomas.
One more likelihood is not to completely reverse the course of development. The first time, Trumpp’s team has succeeded in reprogramming mature human tissue in such a way that a defined form of induced neural stem tissue is produced that can multiply almost indefinitely. “We used four genetic factors like Yamanaka, but different styles for our reprogramming, inches explains Marc Christian Thier, first author of the study. “We assumed that our factors will allow reprogramming to an early period of development of the nerves. ”
In the past, other research groupings also reprogrammed connective tissues cells into mature sensors cells or neural progenitor cells. However, these synthetically produced nerve cells often could not be broadened and can therefore hardly be used for therapeutic purposes. “Often, it was obviously a heterogeneous mixture of different mobile types that might not exist in the body under physiological conditions, inches said Andreas Trumpp describing the problems.
Together with stem cell researcher Outspoken Edenhofer from the University or college of Innsbruck and neuroscientist Hannah Monyer from DKFZ and the Heidelberg University or college Hospital, Trumpp and his team have succeeded in reprogramming different human tissue: connective tissue cells of the skin or pancreatic as well as peripheral white blood cells. “The origin of the pv cells had no effect on the properties of the stem cells, inches said Thier. In particular, the likelihood of taking out neural stem cells from the blood of patients without invasive intervention is a decisive benefits for future therapeutic approaches.
Precisely what is special about the reprogrammed tissue of the Heidelberg scientists is that they are a homogeneous cell type that resembles a period of neural stem tissue that happens during the wanting development of the stressed system. “Corresponding cells are present in mice and probably also in humans during early embryonic brain development, ” said Thier. “We have described here a fresh neural stem cell key in the mammalian embryo.
These kinds of so called “induced Nerve organs Plate Border Stem Cells” (iNBSCs) have a extensive development potential. The iNBSCs of the Heidelberg experts are expandable and multipotent and can develop in two different directions. On the one hand, they can take the road of development to mature nerve tissues and their supplier tissues, the glial cells, i. e. become cells of the main nervous system. Upon the other hand, they can also develop into cells of the neural crest, from which different cell types emerge, for example peripheral sensitive neural cells or cartilage and bones of the skull.
The iNBSCs thus form a perfect basis for producing 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 named “self” by the immune system and are not rejected, inch explains Thier.
The CRISPR/Cas9 gene scissors can be used to modify the iNBSC or repair hereditary defects, as the researchers have demostrated in their tests. “They are therefore of interesting both for basic research and the research for new active ingredients and for the development of regenerative therapies, for example in patients with diseases of the anxious system. However until we can use them in patients, a lot of research work will still be necessary, ” emphasizes Trumpp.