Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration

Martina Balli, Francesca Vitali, Adrian Janiszewski, Ellen Caluwé, Alvaro Cortés-Calabuig, Sebastien Carpentier, Robin Duelen, Flavio Ronzoni, Lukas Marcelis, Francesca Maria Bosisio, Riccardo Bellazzi, Aernout Luttun, Maria G.Cusella De Angelis, Gabriele Ceccarelli, Frederic Lluis, Maurilio Sampaolesi

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Defective cell migration causes delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective and affordable treatment able to improve wound healing capacity. However, the precise molecular mechanism through which AMG exhibits its beneficial effects remains unrevealed. Herein we show that AMG improves skin re-epithelialization by accelerating the migration of fibroblasts and keratinocytes. More specifically, AMG-treated wounds showed improvement of indispensable events associated with successful wound healing such as granulation tissue formation, organized collagen content, and newly formed blood vessels. We demonstrate that AMG is enriched with a pool of WH-associated growth factors that may provide the starting signal for a faster endogenous wound healing response. This work links the increased cell migration rate to the activation of the extracellular signal-regulated kinase (ERK) signaling pathway, which is followed by an increase in matrix metalloproteinase expression and their extracellular enzymatic activity. Overall we reveal the AMG-mediated wound healing transcriptional signature and shed light on the AMG molecular mechanism supporting its potential to trigger a highly improved wound healing process. In this way, we present a framework for future improvements in AMG therapy for skin tissue regeneration applications.

Original languageEnglish (US)
Pages (from-to)1520-1538
Number of pages19
JournalCell Death and Differentiation
Volume27
Issue number5
DOIs
StatePublished - May 1 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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