MIT Engineers Develop Breakthrough Method to Convert Skin Cells Directly into Neurons for Cell Therapy

In a groundbreaking study publishedin Cell Systems, researchers from the Massachusetts Institute ofTechnology (MIT) have developed a novel method to directly convert skin cellsinto neurons, bypassing the need for intermediate stem cell stages. Thisinnovative approach could revolutionize cell therapies for conditions such asspinal cord injuries and neurodegenerative diseases.

Credits:MIT News

Simplified Conversion Process

Traditional methods of transforming onecell type into another, such as converting a skin cell to a neuron, typicallyrequire inducing the skin cell into a pluripotent stem cell (iPSC) beforedifferentiating it into the desired cell type. However, this process istime-consuming and often results in low conversion efficiency, with many cellsfailing to fully mature.

The MIT team, led by Katie Galloway, the W.M. Keck Career Development Professor in Biomedical Engineering and ChemicalEngineering, has devised a more efficient approach. By using a combination ofjust three transcription factors and two genes that promote cell proliferation,the researchers were able to directly convert mouse skin cells into motorneurons. This method eliminates the need for the iPSC intermediate stage,significantly streamlining the conversion process.

High Conversion Efficiency

The new method boasts a high conversionefficiency, producing more than 10 neurons from a single skin cell. Thisrepresents an 11-fold increase compared to previous direct conversiontechniques, which yielded less than 1% efficiency. The researchers achievedthis breakthrough by delivering all three transcription factors using a singlemodified virus, ensuring proper expression levels in each cell. Additionally,they employed a different virus to introduce the two genes that drive cellsinto a highly proliferative state, further enhancing neuron production.

Potential for Cell Therapy

The ability to efficiently generate largequantities of motor neurons from skin cells holds significant promise for celltherapy applications. Motor neurons are critical for controlling musclemovement and are often damaged in spinal cord injuries and diseases likeamyotrophic lateral sclerosis (ALS). By transplanting these lab-grown neuronsinto affected areas, researchers hope to restore lost function and improvepatients' quality of life.

As a first step toward clinicaltranslation, the MIT team demonstrated that their motor neurons could beengrafted into the brains of mice, where they integrated with host tissue.These neurons showed measurable electrical activity and calcium signaling,indicating their ability to communicate with other neurons.

Future Directions

While the current study focuses on mousecells, the researchers are optimistic that their method can be adapted forhuman cells. They are currently working to improve the efficiency of human cellconversion and explore the potential of these neurons for treating spinal cordinjuries and neurodegenerative diseases.

"We were able to achieve yields thatmake these cells viable candidates for cell replacement therapies," saidGalloway. "This is where reprogramming technologies can take us, openingup new possibilities for treating a wide range of neurologicalconditions."

This breakthrough not only simplifies thecell conversion process but also accelerates the development of neuron-basedtherapies, bringing hope to patients suffering from debilitating neurologicaldiseases.