A groundbreaking discovery in regenerative medicine is making waves, as MIT researchers have successfully developed a method to convert skin cells directly into brain cells. This innovative technique bypasses the conventional stem cell stage, achieving unprecedented efficiency in cellular transformation.
Traditionally, creating stem cells for medical applications involved controversial practices, such as harvesting them from embryonic tissue. However, a significant advancement came in 2006 when Japanese scientists discovered a way to reverse mature cells into induced pluripotent stem cells (iPSCs), which could then be transformed into various cell types. Despite this, the process faced efficiency hurdles, with many cells getting stuck in intermediate stages. While advancements have improved the conversion rate significantly, scientists continued searching for more direct and effective solutions.
Now, researchers at MIT have successfully eliminated the intermediate step, allowing for the direct transformation of skin cells into brain cells with remarkable efficiency. According to the study, the new technique boasts a conversion rate exceeding 1,000%, meaning that for every original skin cell, more than ten functional motor neurons are produced.
“Oftentimes, one of the challenges in reprogramming is that cells can get stuck in intermediate states,” explained Katie Galloway, senior author of the study. “So, we’re using direct conversion, where instead of going through an iPSC intermediate, we’re going directly from a somatic cell to a motor neuron.”
The process involves using a combination of three transcription factors—NGN2, ISL1, and LHX3—delivered via viral vectors to induce direct cell transformation. Additionally, the researchers introduced genes that trigger cellular proliferation before conversion, further enhancing efficiency.
“If you were to express the transcription factors at really high levels in nonproliferative cells, the reprogramming rates would be low, but hyperproliferative cells are more receptive,” Galloway noted. “It’s like they’ve been potentiated for conversion, and then they become much more receptive to the levels of the transcription factors.”
Experiments conducted on mouse skin cells confirmed the effectiveness of this approach, yielding fully functional motor neurons that exhibited electrical activity and calcium signaling. Furthermore, when these lab-grown neurons were transplanted into living mice, they successfully integrated with existing brain cells, showcasing their potential for medical applications.
A similar version of the technique was tested on human cells, though the efficiency remains lower at 10–30%. However, this still marks a significant improvement over previous methods, and researchers are optimistic about refining the process to increase its effectiveness.
If further advancements are made, the technique could be a game-changer for treating neurodegenerative diseases like ALS by regenerating lost neurons. Moreover, its applications may extend beyond neurons to other cell types, paving the way for revolutionary therapies in regenerative medicine.
The findings have been published in the journal Cell Systems.
Source: MIT
