Professor Pengtao Liu and Dr. Dong Han were recently interviewed by the Croucher Foundation to discuss their findings in the field of neural stem cells. The article is available here.

New neural stem cell type could impact treatment of neurological diseases

Identification of pNSCs in the mouse. a. pNSCs distribute along the bronchi
of the mouse postnatal (shown in figure) and adult lung. These cells are
specifically marked by Sox1 and co-express Sox2. b. pNSCs can be isolated
and cultured in vitro for at least 50 passages. c. Schematic diagram depicting
the origin, migration, and distribution of pNSCs.

Regenerative medicine holds tremendous promise for transforming the treatment of neurological disorders. Stem cell therapy is at the forefront of regenerative medicine, with significant research focused on using various types of stem cells to repair or regenerate damaged neural tissues.

For many years, it was believed that neural stem cells were confined to the brain and spinal cord. However, a recent discovery by researchers at the University of Hong Kong and the Max Planck Institute for Molecular Biomedicine has changed that. They have identified peripheral neural stem cells (pNSCs) derived from mouse limb and lung tissues for the first time. Their findings have been published in Nature Cell Biology.

Croucher News recently spoke to Professor Pengtao Liu, S Y and H Y Cheng Professor in Stem Cell Biology and Regenerative Medicine, who also manages InnoHK Centre for Translational Stem Cell Biology, and Dr Dong Han from the School of Biomedical Sciences at the University of Hong Kong’s Faculty of Medicine about their remarkable discovery and its implications.

The researchers found neural stem cells throughout the bodies of mice, in the peripheral nervous system (PNS), the parts of the nervous system outside the brain and spinal cord. These peripheral neural stem cells, or pNSCs, seem to have originated in the central nervous system but migrated outwards, say the researchers. They have found the cells in “the legs, the tail and the lungs, and also in the thymus, intestine, skin, muscle…” Dr Han told us.

There was an element of chance in this discovery initially. In a project Han was carrying out with Professor Scholer from the Max Planck Institute for Molecular Biomedicine, they had set out to perform cell-fate transdifferentiation – converting one kind of adult cell into another kind. Specifically, they were trying to convert somatic cells (ordinary body cells like skin or muscle cells) into neural stem cells.

Han told us that during the experiment, “We found…some unexpected results.” They discovered they didn’t need to transdifferentiate the cells, as they found some neural stem cells already in the somatic cells. “We found that these cells are endogenous [naturally present], which we did not expect at all at the beginning… This discovery changed the whole concept of the study.”

This marked the start of extensive efforts to validate their discovery, which Han described as "exciting". The researchers used techniques such as lineage tracing (similar to creating a family tree for cells) and single-cell RNA sequencing to confirm that these cells were indeed a kind of neural stem cell.

It's one thing to find such cells in mice, however, and another to discover them in humans. So the team scoured existing research data for these cells, which may have been observed but not recognised in previous research.

After they analysed published data, they proposed that these cells can be found in humans. “We know they are there,” said Professor Liu. He added, “And we are doing experiments to physically isolate the cells. But working with human cells is not that straightforward because we have to obtain proper ethical approvals for us to do anything related to human cells.”

Although there is more basic research to do, the researchers can see that the pNSCs are similar to neural stem cells taken from the central nervous system... “Once they are cultured … in vitro … they are basically identical," said Han.

The discovery of these pNSCs could have significant therapeutic potential as scientists develop more techniques for using stem cells in regenerative medicine to combat a range of neurological diseases.

For one thing, the cells would be far more accessible, perhaps via a simple biopsy, Han suggested, compared to invasive brain surgery. They would also be authentic, “bona fide neural stem cells”, as Liu called them, compared, say, to transdifferentiation-derived or induced Pluripotent Stem Cells (iPSCs)-derived neural stem cells, where adult cells are reprogrammed or differentiated in the lab.

Another advantage, says Han, relates to the risk of tumours. “If we compare our peripheral neural stem cell to some other neural stem-like cells which derive from the pluripotent cell... our cells will not generate a tumour.”

The possible future that beckons is one of personalised, precision medicine where patients could, in effect, be their own donors. As such, there would be no risk of immune rejection. In such a future world, “Everyone can get their own neural stem cell just by some very simple biopsy sample collection. Then you will have your own neural stem cell,” speculated Han.

But there may be a catch. Liu told us that "These types of cells get fewer and fewer once we grow up.” These neural stem cells are numerous in a newborn baby. But the older we get, the fewer such cells are to be found.

This would mean that collection of pNSCs for individuals would need to take place at an early age, perhaps decades before any neurological conditions developed. The cells would then need to be stored for the long term, against possible future need.

At present, all of that is just speculation. Right now, the researchers’ focus is on obtaining approval for human extraction of pNSCs, understanding their migration pathways and differentiation mechanisms, and identifying optimal tissue sources for cell extraction.

The practical and ethical obstacles are formidable. Nevertheless, the researchers are optimistic about the future and confident that this work will have a long-term impact. “I think this could be a kind of a new direction in the neural stem cell field,” said Han.

And Liu told us, “We are confident that these cells will be at least alternatives as cells for cell-based therapy for neurodegenerative diseases or other types of diseases.”