Connection found between collagen IV and tissue regeneration

9 August 2021

Understanding of the regenerative function of stem cells has received a boost following a discovery by a research team led by Professor Danny Chan (Croucher Senior Research Fellowship 2014) at the University of Hong Kong (HKU), potentially moving scientists a step closer to increasing healing ability in people.

The School of Biomedical Sciences researchers have identified the role of collagen IV in regulating how stem cells divide or change in planarian, free-living flatworms with strong regenerative powers. Close to one-third of these worms’ bodies are made of stem cells. When a worm is cut into smaller pieces, each piece can regenerate into a complete organism within a few weeks.

How planarian can keep so many stem cells remains a mystery, and has fascinated biologists for over a century.

The HKU study was carried out in collaboration with researchers from the University of Toronto, who are also affiliated to The Hospital for Sick Children and Ontario Institute for Cancer Research.

Stem cells reside within a microenvironment called the stem cell niche, comprising different types of extracellular matrix proteins (ECM), which provide signals to govern the stem cells. Collagen IV is an ancient ECM that has been highly conserved through evolution and is present in all mammals.

The research team discovered that when collagen IV is removed in planarian, stem cells divide much faster but lose their ability to become cells of other tissue types for regenerative purposes.

The division process is facilitated by a growth factor, nrg-7, produced by neurons. Nrg-7 stimulates stem cell proliferation, and increases after removal of collagen IV. As a result, stem cells only proliferate, and are unable to turn into other cell types to repair or maintain planarian tissues.

The study has been published in Proceedings of the National Academy of Sciences of the United States of America (PNAS).

In humans, resident adult stem cells allow an individual’s body to recover from mild damage to tissues and organs, but not major injuries.

“Our finding of an extracellular matrix protein as part of the environment in which planarian can keep stem cells is an important step, with the hope that we can mimic this in humans to rebuild missing tissues,” Chan said. “As a bone biologist, I would like to see, one day, we can regrow a missing digit.”

One goal in connection with this would be to build an artificial stem cell “niche”, capable of housing a large number of human stem cells, which can then be applied to damage sites and used to help regenerate tissues.



Danny Chan is a Professor at the School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong (HKU). He graduated from the University of Melbourne, with a Bachelor of Science (Hons), Master of Science, and Doctor of Philosophy. He is currently the holder of the S Y and H Y Cheng Professorship in Stem Cell Biology and Regenerative Medicine as well as Assistant Dean (Research Postgraduate Studies) at HKU.


To view Professor Chan’s Croucher profile, please click here.