In breakthrough new research described as "somewhat mind-boggling," a team at Stanford University has developed a technique than can transform human immune cells found in a regular blood sample into functional neurons in just three weeks.
The research follows on from several years of work going back to 2010 when the team first developed this technique showing mouse skin cells could be directly transformed into mouse neurons without the cells entering a state called pluripotency. Previously it was thought that to reprogram a human cell it would need to first be transformed into what is called an induced pluripotent stem cell (iPSC).
After initially demonstrating that this time-consuming step could be skipped in mouse models, the team then showed the process could be replicated using human skin cells in 2011. But even then, the process of transforming skin cells into neurons was not as efficient or easy as one would hope.
"Generating induced pluripotent stem cells from large numbers of patients is expensive and laborious," says Marius Wernig, senior author on the new study. "Moreover, obtaining skin cells involves an invasive and painful procedure. The prospect of generating iPS cells from hundreds of patients is daunting and would require automation of the complex reprogramming process."
This new study demonstrates a breakthrough technique that can produce as many as 50,000 neurons from as little as 1 milliliter of blood, regardless of whether the sample is fresh or had been previously frozen. By adding just four proteins, in one simple step, the team was able to transform human T cells into functional neurons.
"It's kind of shocking how simple it is to convert T cells into functional neurons in just a few days," says Wernig. "T cells are very specialized immune cells with a simple round shape, so the rapid transformation is somewhat mind-boggling."
The initial goal of the research is to be able to enhance study of neurological disorders such as autism and schizophrenia by examining functional neuronal activity in a large number of patients. At this stage, the neurons created through the technique are unable to form mature synapses, so they are not useful for therapeutic outcomes, but they will allow scientists to mimic certain brain diseases in a laboratory context, rapidly accelerating our understanding of some complex neurological disorders.
"We now have a way to directly study the neuronal function of, in principle, hundreds of people with schizophrenia and autism," explains Wernig. "For decades we've had very few clues about the origins of these disorders or how to treat them. Now we can start to answer so many questions."
The study was published in the journal PNAS.