Directly Transforming Skin Cells into Brain Cells Achieves a Tenfold Increase in Success

MIT scientists have made a significant breakthrough in regenerative medicine by developing a highly efficient method to convert skin cells directly into brain cells, eliminating the need for an intermediate stem cell stage.

Traditionally, generating stem cells for medical treatments required harvesting them from embryonic tissue, raising ethical concerns. That changed in 2006 when Japanese researchers discovered how to reprogram mature cells into induced pluripotent stem cells (iPSCs), which can then transform into various cell types for treatment. However, this Nobel Prize-winning discovery has its challenges—many cells get stuck in transitional stages, reducing overall efficiency. While early methods had success rates below 0.1%, advancements have pushed that number closer to 100% in some cases.

Now, MIT researchers have found a way to bypass the stem cell stage entirely, directly converting one cell type into another with remarkable efficiency—over 1,000%. Essentially, each source cell produces 10 or more target cells, a dramatic improvement over previous techniques.

“Oftentimes, one of the challenges in reprogramming is that cells can get stuck in intermediate states,” explains Katie Galloway, senior author of two studies on the new technique. “By using direct conversion, we skip the iPSC stage and go straight from a somatic cell to a motor neuron.”

The original method relied on four genes encoding transcription factors delivered via viral vectors to transform skin cells into iPSCs. In this new approach, researchers tested six previously studied transcription factors, experimenting to find the minimal yet most effective combination. After extensive testing, they identified three key factors—NGN2, ISL1, and LHX3—that could complete the conversion.

Enhancing Efficiency: Optimized Gene Delivery for Superior Cell Reprogramming

By packaging all three factors into one viral vector and using a second to stimulate proliferation, they enhanced reprogramming efficiency.

“Hyperproliferative cells respond better to transcription factors, making the process more efficient,” Galloway explains.

The team converted mouse skin cells into motor neurons with over 1,000% efficiency. The new neurons showed electrical activity, integrated into mouse brains, and formed connections.

The researchers also adapted the technique for human cells, though current efficiency ranges from 10 to 30%. While lower than the mouse model, it’s a vast improvement over early iPSC methods, which had just a 0.1% success rate. The team aims to refine the process to boost human cell conversion rates further.

If successful, this approach could revolutionize treatments for neurodegenerative diseases like ALS by regenerating motor neurons. Beyond that, the method holds potential for converting cells into other specialized types, opening doors for a wide range of regenerative therapies.

Read Original Article: New Atlas

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