The ECM in tissue repair and development

The extracellular matrix (ECM) is essential in regulating biological function, yet is still largely unexplored and represents a great opportunity for furthering our understanding of tissue biology. We have been investigating the ECM and how it regulates two sides of the same coin in tissue function: development and regeneration. First, we will show that in human pluripotent stem cells, the stiffness of the basement membrane determines polarity signalling and epithelial structure. which in turn regulates essential developmental and wound-healing signals like BMP. This finding implicates the basement membrane ECM in regulating epithelial structure and signalling. We believe the finding is likely to be general to regeneration and wound-healing. Second, using the digit tip as a well-controlled model of mammalian regeneration after injury, we identified the ECM as the major driver of the post-injury switch between fibrosis and regeneration. We showed that the tissue mechanics of fibrotic regions differ significantly from regenerative regions, and these differences are driven largely by dramatic differences in hyaluronic acid (HA) content. We showed not only that the HA matrix is an essential regulator of ECM structure, but that depleting it turns a typically regenerative tissue fibrotic after injury, and a typically fibrotic tissue regenerative. The findings suggest ECM plays an essential role in mammalian regeneration, and could also be the key to resolving chronic inflammation and fibrosis. With these studies, we conclude that the ECM is a major, overlooked player in tissue function, development and repair.

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Part of a mini-series of joint seminars between BDD and PCC. Don’t miss the talk given by Ewa Paluch “Cross-talk between cell mechanics, cell shape and cell fate” on 27/05 11:00 am at Amphithéâtre Hélène Martel-Massignac (BDD).