Researchers advanced the age of human neurons beyond what was previously possible

Although previous researchers have differentiated stem cells to become neurons, those neurons were functionally immature -- resembling neurons from embryonic or early postnatal stages. The limited maturation obtained with current stem cell culture techniques diminish their potential for neurodegeneration studies.

To create the mature neurons, the team used "dancing molecules," a breakthrough technique introduced last year by Northwestern professor Samuel I. Stupp. The team first differentiated human iPSCs into motor and cortical neurons and then placed them onto coatings of synthetic nanofibers containing the rapidly moving dancing molecules.

Not only were the enriched neurons more mature, they also demonstrated enhanced signaling capabilities and greater branching ability, which is required for neurons to make synaptic contact with one another. And, unlike typical stem cell-derived neurons which tend to clump together, these neurons did not aggregate, making them less challenging to maintain.

With further development, the researchers believe these mature neurons could be transplanted into patients as a promising therapy for spinal cord injuries as well as neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson's disease, Alzheimer's disease or multiple sclerosis.

The mature neurons also present new opportunities for studying neurodegenerative diseases like ALS and other age-related illnesses in culture dish-based in vitromodels. By advancing the age of neurons in cellular cultures, researchers could improve experiments to better understand late-onset diseases.

"This is the first time we have been able to trigger advanced functional maturation of human iPSC-derived neurons by plating them on a synthetic matrix," said Northwestern's Evangelos Kiskinis, co-corresponding author of the study. "It's important because there are many applications that require researchers to use purified populations of neurons. Most stem cell-based labs use mouse or rat neurons co-cultured with human stem cell-derived neurons. But that does not allow scientists to investigate what happens in human neurons because you end up working with a mixture of mouse and human cells."

"When you have an iPSC that you manage to turn into a neuron, it's going to be a young neuron," said Stupp, co-corresponding author of the study. "But, in order for it to be useful in a therapeutic sense, you need a mature neuron. Otherwise, it is like asking a baby to carry out a function that requires an adult human being. We have confirmed that neurons coated with our nanofibers achieve more maturity than other methods, and mature neurons are better able to establish the synaptic connections that are fundamental to neuronal function."(ANI)