Researchers have grown key brain cells linked to MND and damaged in spinal injuries, opening a path to better disease models and regenerative therapies.
The findings lay foundations for disease models and potentially regenerative treatments for conditions including amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease, and spinal cord injury.
Corticospinal neurones are crucial cells that degenerate in ALS. Damage to these cells’ long axons, the extensions that run from cell bodies in the brain through the spinal cord to spinal motor neurones, underlies the loss of voluntary, skilled movement seen after spinal cord injury.
The study was conducted by researchers at Harvard University in the US.
Co-lead author Kadir Ozkan was a postdoctoral fellow in senior author Jeffrey Macklis’ lab at the time of the study.
Ozkan said: “To realistically model diseases and screen for potential treatments, or to regenerate neurones that are damaged in spinal injuries, we need reliable approaches to accurately differentiate progenitor cells into these specific types of neurones.
“Generic or regionally similar neurones do not adequately reflect the selective vulnerability of neurone subtypes in most human neurodegenerative diseases or injuries.”
Progenitor cells, also known as adult or parent stem cells, can develop into more specialised cell types.
Senior author Jeffrey Macklis, professor at Harvard’s Department of Stem Cell and Regenerative Biology, said: “There are currently no appropriate in vitro models for investigating the selective vulnerability and degeneration of corticospinal neurones in ALS or to explore potential routes to regeneration in spinal cord injury. This critically limits the relevance of much existing research.”
The team identified a subset of progenitor cells in the postnatal and adult cortex that can be captured and differentiated in the lab into neurones with unique characteristics of corticospinal neurones.
They designed a multi-component gene expression system to precisely fine-tune the regulatory signals the progenitor cells require.
This enabled them to drive cells down a highly specific differentiation route where they acquire the hallmark characteristics of corticospinal neurones.
The programming produced mature neurones from the progenitors with the same distinct shape, key cell markers, molecular-gene expression and electrical connectivity as seen in native corticospinal neurones.
Future research is needed to assess how these reprogrammed corticospinal neurones integrate and function under physiological conditions and in models of trauma or neurodegeneration.
Macklis said: “We have identified a subset of cortical progenitor cells with strong potential to differentiate into specialised neurones for disease modelling in ALS and spinal cord injury, and for regenerative therapies.
“Importantly, SOX6+/NG2+ progenitor cells are widely distributed in the cortex, already positioned near sites of degeneration or pathology.
“This adds substantially to their therapeutic potential, pending further study, including with human pluripotent stem cell-derived cortical progenitors.”
