Human immune cells in the blood can be converted directly into functional neurons in the laboratory in about three weeks, with the addition of just four proteins, a team of researchers from the Stanford University School of Medicine (USA) has found. USA). They are not perfect neurons, but they may be used to better understand diseases such as Alzheimer’s and autism and enable new treatments.
This dramatic transformation does not require cells to become pluripotent (a flexible developmental stage in which cells can develop into almost any type of tissue), but instead occurs through a more direct process called transdifferentiation from cells. T lymphocytes, a type of white blood cell responsible for providing defenses to the immune system.
The conversion occurs with relatively high efficiency (generating up to 50,000 neurons with 1 milliliter of blood) and can be achieved with fresh or previously frozen and stored blood samples, greatly improving the opportunities for the study of neurological disorders.
“Blood is one of the easiest biological samples to obtain,” says study leader Marius Wernig. “Almost all patients admitted to a hospital leave a blood sample, and these samples are often frozen and stored for later study. This technique is a breakthrough that opens the possibility of learning about complex disease processes through study of a large number of patients “.
According to the authors in the study published in the Proceedings of the National Academy of Sciences , the generation of induced pluripotent stem cells from large numbers of patients is costly and laborious, and hundreds of individual and patient-specific samples are needed to deduce the relative contributions of dozens or more disease-associated mutations.
Finding an easier and more efficient way to generate patient-specific neurons was the key.
An unusual transformation
In the new study, the scientists focused on highly specialized immune cells called T cells that circulate in the blood. T cells protect us from disease by recognizing and killing infected or cancer cells. In contrast, neurons are long, thin cells capable of conducting electrical impulses along their length and passing them from one cell to another. But despite the cells’ vastly different shapes, places, and biological missions, the researchers found that it was unexpectedly easy to complete their mission .
“It’s shocking how simple it is to turn T cells into functional neurons in just a few days,” Wernig said. “T cells are very specialized immune cells with a simple round shape, so the rapid transformation is amazing.”
The resulting human neurons are not perfect. They lack the ability to form mature synapses, or connections, with each other. However, they are capable of carrying out the main fundamental functions of neurons, and the authors hope to be able to further optimize the technique in the future.
“We now have a way to directly study the neural function of initially hundreds of people with schizophrenia and autism. For decades we have had very few clues about the origins of these disorders or how to treat them. Now we can begin to answer many questions.” Wernig concludes.
Reference: Transdifferentiation of human adult peripheral blood T cells into neurons. Koji Tanabe et al. PNAS, June, 2018. 201720273. DOI: https://doi.org/10.1073/pnas.1720273115
