Scientists Use iPSCs to Grow Mature Neurons to Study Neurodegenerative Diseases

A research team led by Northwestern University has successfully created the first highly mature neurons from human induced pluripotent stem cells (iPSCs) using a synthetic material. This finding opens up new opportunities for mechanism research and therapy development for neurodegenerative diseases as well as traumatic injuries. 

Cell Stem Cell recently published the exciting findings from the research team’s work.

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‘Dancing Molecules’ Technique to Create Mature Neurons

Previous researchers have tried multiple approaches to differentiate stem cells into neurons; however, those neurons were functionally immature, which diminished their potential in neurodegeneration studies as the process of degeneration only appears in mature neurons in adults.

In this novel study, the scientists used a breakthrough technique named ‘dancing molecules,’ first introduced in 2021.

The extracellular matrix is fundamental for developing cells in the lab since it provides structural support, regulates cell signaling and differentiation, and modifies an adequate environment for cellular growth. Thus, scientists aimed to recreate the extracellular matrix to achieve maturation and functionality similar to neurons in the nervous system under physiological conditions.

The initial step was to differentiate the human iPSCs into the motor and cortical neurons to later place them on nanofibers composed of ‘dancing molecules.’ Those nanofibers with higher molecular motion improved human neuronal cultures by showing greater maturity, less aggregation, and more intense signaling. This model has the potential to better understand late-onset diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS).

New Advancement in Cell Replacement Therapy

As for treating neurodegenerative diseases, the team took skin cells from an ALS patient and turned them into patient-specific motor neurons, the weakened type of neuron in the disease. These neurons were cultured for two months on the synthetic materials to develop similar characteristics of the ALS patients. This method provided a new window to study ALS by the extent of maturation it could achieve and could also be used to test potential therapies derived from human cells.

Moreover, the success of iPSC-derived mature, enhanced neurons provided new insight into cell replacement therapy as those neurons could be transplanted into patients with spinal cord injuries or neurodegenerative diseases without generating rejection as the origin of the neuron is from the particular patient.   

The main challenge to making this therapy feasible at the clinical stage is to elevate the extremely low yield of transformation while simultaneously controlling the proper maturation stage. Thus, the scientists planned to integrate the successful coating in this study into the large-scale manufacturing of patient-derived neurons for future usage in cell transplantation therapies. 

Author

Nai Ye Yeat