Human neurons from fibroblasts: direct reprogramming
Skin cells have learned to turn into neurons
Moreover, it was possible to achieve this by reprogramming directly, without the stem cell stage. According to the authors, they hope that their research will help in the creation of treatments for Huntington's disease – a severe and currently incurable neurological disease.
It is believed that in this disease, special neurons are affected – the median spike neurons of the striatum, which are largely responsible for controlling movement. It was these cells that researchers from the Washington University Medical School in St. Louis managed to obtain.
Advantages of direct reprogrammingCurrently, in cellular medicine, either embryonic cells or cells of an adult organism are mainly used, to which pluripotency is restored.
These are so-called induced pluripotent stem cells, which can turn into cells of almost any organs and tissues. For the first time such cells were obtained by Professor Yamanaka from Kyoto University in 2006, for which he received the Nobel Prize in 2012.
But there is a serious danger in induced pluripotent stem cells – there is always a risk that they will not cope with pluripotence and develop into a cancerous tumor. This is one of the reasons that hinders the use of this technology in clinical practice.
In the last few years, an alternative to this method has appeared. Scientists have learned to directly reprogram adult cells from one type to another, bypassing the dangerous stem stage.
For example, there are already ways to convert human skin cells into blood cells. Or, for example, human fibroblasts can be turned into cardiomyocytes.
Bioengineers have also managed to directly obtain neurons from skin cells, although until now such studies have been conducted only on mice.
How to get neurons from human fibroblastsIn the current study, the authors obtained median spike neurons from human fibroblasts – connective tissue cells that are part of the skin.
To reprogram fibroblasts, the study's lead author, Dr. Andrew Yoo, and his colleagues processed their micro-RNA. In their previous work, scientists have already shown that the reprogramming of skin cells into neuronal cells can occur using two micro-RNAs - miR-9 and miR-124. However, at the same time they turn into different types of neurons. To get a special type of neurons – median spines – scientists also used transcription factors, which are located in the part of the brain where there are just a lot of these neurons.
Fibroblasts (left) transformed into spike neurons (right)
Pictures from the press release of Washington University in St. Louis
Human skin cells reprogrammed directly into brain cells – VM
"With the help of micro-RNA, we turned skin cells into neurons. And the transcription factor launched a program to get not just neurons, but a special kind of them – median spines. We think that with the help of different transcription factors, it is possible to control this process and get different neurons," says Matheus B. Victor, one of the authors of the study.
TransplantationThe scientists then placed the resulting cells in the brains of laboratory mice.
Their survival was proven – after six months, the cells retained their functions and worked like ordinary neurons.
"We were able to show that the cells that we transplanted into the brains of mice not only survived, but also functioned like ordinary real neurons. It is known that the median spike neurons interact with other parts of the brain. We were able to show that the neurons we received work exactly the same way. This is one of the most important achievements of our research," says Andrew Yu.
Now scientists are planning to find out what will happen if the neurons obtained in this way are introduced into the body of laboratory mice with Huntington's disease, i.e. to understand whether cell therapy of this disease is possible.
An article describing the reprogramming of human skin fibroblasts into neurons was published in the latest issue of the journal Neuron (Victor et al., Generation of Human Striatal Neurons by microRNA-Dependent Direct Conversion of Fibroblasts).
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