Epithelial-to-mesenchymal transition for tendon regenerative medicine strategies

Jun 30, 2022, 11:20 AM
Room: S3 B

Room: S3 B


Barboni, Barbara (University of Teramo)


"Epithelial-to-mesenchymal transition (EMT) is a key event in embryo development and post-natal life in which epithelial cells undergo to a transdifferentiation into mesenchymal cells by acquiring a mobile state. This cell transitioning process recognizes the activation of signaling pathways which occur under controlled environments in response to factors controlling stem cell epigenetic reprogramming, self-renewal and differentiation (1). The investigation of EMT processes controlling tissue patterning and organization as well as disregulating healing processes leading to fibrosis, as for tendinopathies, has been addressed for enabling the advancement of regenerative medicine strategies based on the control of EMT-mediated events in generating a favorable local environmental of stem cell-host tissue dialogue as well as of repairing feedback loop between extracellular matrix (ECM) and progenitor/host cells (4).
In order to verify the role exerted by EMT mediated decision during tenogenesis an epithelial stem cell source derived from the amnion were used to analyse the mechanisms underlying the recovery of tendon microarchitecture and function in relation to cell phenotype. To this aim validated in vitro protocols have been used in order to control the phenotype status of AECs before transplantation by obtaining three subset of cells, starting from a unique genome makeup: epithelial (eAECs), mesenchymal (mAECs) (2) and tendon-like (tdAECs) cells (5). The results of this research demonstrate that eAECs and tdAECs are the most suitable phenotypes to use in order to accelerate the process of regeneration in experimental injured tendons. The healing advantage obtained using these two AECs’ phenotypes is however obtained through two different underlying mechanisms. Epithelial AEC were able to positively influence the process of tendon healing mainly through the modulation of the host tissue immune environment, targeting a potential shift from pro-inflammatory and pro-fibrotic to pro-regenerative cellular responses, which probably led to a reduced infiltration of inflammatory cells responsible of the ordered deposition of ECM components. On the other hand tdAECs transplantation played the major role in accelerating the deposition and organization of the ECM without strongly influencing the host immune system. Thus, the ability to control the cell phenotype by reproducing the epithelial-mesenchyme-tenodifferentiation stepwise process, allowed us to comprehensively determine how to drive the regenerative process by supporting a favorable stem cell-host tissue cross-talk. Studies that probe the mechanisms underlying the relationship between EMT and EMT/ECM interactions thus represent the next steps forward in elucidating strategies for reducing fibrosis.

1. Wilson M. M. et al. Trends in Cancer 2020;
2. Canciello A et al. Sci Rep, 2017;
3. Barboni B et al. J Tissue Eng Regen Med, 2018;
4. Russo V et al. Cells 2020;
5. Barboni B et al. PLOS ONE 2012

Acknowledgments: This research is funded by H2020-MSCA-ITN-EJD-P4 FIT grant agreement No 955685."


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