Tuesday , January 31 2023

Study: Human blood cells can be directly reprogrammed into neural stem cells – (Details)


Scientists from the German Cancer Research Center (DKFZ) and the HI-STEM * stem cell institute in Heidelberg for the first time managed to directly reprogram human blood cells in a previously unknown type of neuronal stem cells. These induced stem cells are similar to those occurring during the early embryonic development of the central nervous system. They can be modified and multiplied unlimitedly in the culture bowl and can be an important basis for the development of regenerative therapies.

It is believed that stem cells are versatile of our tissue: they can multiply unlimitedly and then – if pluripotent embryonic stem cells – generate all possible types of cells. Japanese scientist Shinia Iamanaka acknowledged in 2006 that such cells could be produced in the laboratory – from mature body cells. Four genetic factors alone are enough to reverse the developmental course and produce so-called induced pluripotent stem cells (iPS) that have identical properties with embryonic stem cells. In 2012, the Iamanaka was awarded the Nobel Prize for Medicine for this discovery.

"This has been a major advancement in stem cell research," said Andreas Trumpp, German Center for Cancer Research (DKFZ) and director of HI-STEM in Heidelberg. "This is particularly true of research in Germany, where human embryonic stem cells are not allowed to be created. Stem cells have huge potential for basic research and for the development of regenerative therapies aimed at restoring diseased tissue in patients. However, reprogramming is also associated with problems: for example, pluripotent cells can form zoster-type tumors, so-called teratomas.

The other possibility is not to turn the development of the whole. For the first time, the Trump team succeeded in reprogramming mature human cells in such a way as to produce a defined type of induced neuronal stem cells that can be duplicated almost unlimitedly. "We have used four genetic factors, such as the Iamanaka, but different for our reprogramming," explains Marc Christian Thier, the first author of the study. "We have assumed that our factors will allow reprogramming in the early stage of the development of the nervous system."

In the past, other research groups reprogrammed the connective tissue cells into mature nerve cells or neuronal precursor cells. However, these artificially produced nerve cells were often not able to expand and therefore are difficult to use 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 the researcher of stem cells, Frank Edenhofer of the University of Innsbruck, and neurosurgeon Hann Monier of the DKFZ and the Heidelberg University Hospital, Trumpp and his team succeeded in reprogramming different human cells: connective tissue of the skin or pancreas as well as peripheral blood cells. . "The origin of the cells had no effect on the stem cell properties," Thier said. In particular, the possibility of extracting neural stem cells from the blood of patients without invasive intervention is a crucial advantage for future therapeutic approaches.

What is particularly true with the reprogrammed cells of Heidelberg researchers is that they are a homogeneous type of cell that resembles the stage of neuronal stem cells that occurs during the embryonic development of the nervous system. "Appropriate cells exist in mice and possibly in humans during early embryonic brain development," Thier said. "We have described here a new type of nerve stem cell in the embryo of a mammal.

These so-called "induced border stem cells of the neural plate" (iNBSCs) have a wide development potential. INBSC's Heidelberg scientists are expanding and multipotent and can develop in two different directions. On the one hand, they can go through the development of mature nerve cells and their cellular suppliers, glial cells, i.e. To become central nervous system cells. On the other hand, they can develop into cells of the neural reef, from which various types of cells appear, for example peripheral sensitive nervous cells or cartilage and skull bones.

Thus iNBSCs make an ideal basis for generating a wide range of different types of cells for an individual patient. "These cells have the same genetic material as the donor and therefore the immune system is probably recognized as" self "and not rejected," Thier explains.

CRISPR / Cas9 gene scissors can be used to modify iNBSC or to repair genetic defects, as scientists have shown in their experiments. "Therefore, they are also interesting 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, as long as we can not use them in patients, a lot of research work will still be needed, "Trumpp said.

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