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By understanding and controlling the transcriptional and chromatin mechanisms underlying the plasticity and regenerative capacity of nasal cartilage cells, it may be possible to use those cells for regeneration of the intervertebral disc.

October 23, 2018

The epigenetics of cartilage repair and regeneration


The European Research Council (ERC) has awarded a prestigious ERC Synergy Grant – perhaps the most competitive funding scheme from ERC – to the research groups of Prof. Filippo Rijli from the FMI and Prof. Ivan Martin from the Department of Biomedicine at the University of Basel and the University Hospital of Basel. The funding from ERC will flow into a joint project investigating the regenerative properties of adult nasal cartilage cells with the final goal of using them in vivo to regenerate intervertebral disc.

» Read a more high-level article about this topic on the Uni Basel website

During craniofacial development, Cranial Neural Crest Cells (CNCCs) maintain broad plasticity and the capacity to differentiate into various cell types until they make appropriate cartilage and bone structures in response to local environmental signals. In a study published in Science in 20171), the Rijli group found that CNCC embryonic plasticity involves a specific epigenetic chromatin mechanism regulated by the Polycomb group proteins that maintains genes in a transcriptionally silent but poised state, so that they can be readily switched to an active state in response to position-specific environmental signals.

Do certain CNCC-derived cartilage subpopulations in the adult face maintain similar embryonic-like broad plasticity properties throughout life? And could those cells be used as progenitor source in regenerative medicine? Work from the Martin group2) has shown that adult human CNCC-derived nasal chondrocytes (the cells that make up the cartilage of the nose) have the capacity to regenerate cartilage in a different anatomical location and demonstrated their potential clinical use for knee joint articular cartilage repair3). However, little is known about the molecular mechanisms involved. Therefore the broader utilization of adult nasal chondrocytes for the regeneration of other cartilage types, e.g. the intervertebral discs in the spine, is limited.

“Receiving the ERC Synergy grant represents a great honour for Prof. Martin and myself,” says Rijli. “Our ERC funded proposal will establish fundamental understanding of the biological and molecular processes responsible for the plasticity of adult human nasal chondrocytes. And it offers a paradigm example of scientific and clinical synergies bridging the typically segregated research domains of developmental neuroepigenetics and regenerative medicine. This is a cultural shift!”

In particular, the research program will address whether the regenerative versatility of adult nasal chondrocytes could be explained by conserved epigenetic chromatin mechanisms similar to those in embryonic CNCC-derived chondrocytes. Moreover, the project will investigate how control of the epigenetic chromatin state of nasal chondrocytes from adult humans can regulate their environmental plasticity and capacity to regenerate the intervertebral disc.

The final goal of this synergistic cooperation is to provide enough insights to make it possible to conduct clinical trials in patients with intervertebral disc disease, using nasal chondrocytes to regenerate intervertebral disk. Therefore the ERC-funded study also includes the identification of new cellular markers and culture requirements for human nasal derived chondrocytes. These will be crucial towards definition of quality settings for repeatable clinical outcome.

» Joint media release FMI/University Hospital Basel (in English)
» Gemeisame Medienmitteilung FMI/Universitätsspital Basel (auf Deutsch)
» ERC media release

About Filippo Rijli
Filippo Rijli is a Senior Group leader at the FMI and Adjunct Professor of Neurobiology at the University of Basel. He is interested in the epigenetic and transcriptional mechanisms of craniofacial development and topographic map formation in the brain.
» More about Filippo Rijli 

1) Minoux et al., Science 2017, 355(6332):eaal2913
2) Pelltari et al., Science Translational Medicine 2014, 6(251):251ra119
3) Mumme et al., Lancet 2016, 388(10055):1985-1994

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