Researchers from the University of Illinois report that they can create human motor neurons from stem cells faster and more efficiently than earlier methods. They believe this will help efforts to model human motor neuron development and to better understand and treat spinal cord injuries and motor neuron diseases like amyotrophic lateral sclerosis (ALS). This new approach involves adding signaling molecules to stem cells a few days earlier than previous methods. This aids to increase the number of healthy motor neurons derived from stem cells from 30 to 70 percent and cuts in half the time required to do so.
Study lead, Fei Wang, professor of cell and developmental biology at the University of Illinois, with visiting scholar Qiuhao Qu and materials science and engineering professor Jianjun Cheng, note, “We would argue that whatever happens in the human body is going to be quite efficient, quite rapid. Previous approaches took 40 to 50 days, and then the efficiency was very low—20 to 30 percent. So it’s unlikely that those methods recreate human motor neuron development.” Qu’s new method generates a larger population of mature, functional motor neurons in 20 days. Wang adds, this approach will allow researchers to induce mature human motor neuron development in cell culture as well as allow scientists to identify factors that are important to the process.
Stem cells have the unique property in that they can adopt the shape and function of a number of cell types. Turning stem cells into neurons requires adding signaling molecules at critical periods in their development. Wang and colleagues had previously found a molecule known as compound C that converts stem cells into neural progenitor cells which is an early stage in neuronal cell development. However, coaxing these cells to become motor neurons presented with unusual challenges.
Earlier research added two important signaling molecules six days after exposure to compound C. However, there was limited success. Qu found that adding the signaling molecules at day 3 generated neural progenitor cells that quickly and efficiently differentiated into motor neurons. Wang notes, day 3 represents a previously unrecognized neural progenitor cell stage.
The researchers point out that this new method has immediate application in the lab. For example, stem cells derived from ALS patient’s own skin cells can be observed while they develop into motor neurons. This will provide new insights into disease processes. These cells can also be used to screen for drugs to treat motor neuron diseases. In the future, these motor neurons may be used to restore lost function. Wang notes, “To have a rapid, efficient way to generate motor neurons will undoubtedly be crucial to studying—and potentially also treating—spinal cord injuries and diseases like ALS.”