2. Academic Validation
  3. Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration

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

  • Cell Death Differ. 2020 May;27(5):1520-1538. doi: 10.1038/s41418-019-0433-3.
Martina Balli 1 2,  Francesca Vitali 3 4,  Adrian Janiszewski 1,  Ellen Caluwé 5,  Alvaro Cortés-Calabuig 6,  Sebastien Carpentier 7,  Robin Duelen 1,  Flavio Ronzoni 2 8,  Lukas Marcelis 9,  Francesca Maria Bosisio 9,  Riccardo Bellazzi 8 10,  Aernout Luttun 5,  Maria G Cusella De Angelis 2 8,  Gabriele Ceccarelli 2 8,  Frederic Lluis  # 11,  Maurilio Sampaolesi  # 12 13 14
Affiliations

Affiliations

  • 1 Department of Development and Regeneration, Stem Cell Institute, KU Leuven, B-3000, Leuven, Belgium.
  • 2 Human Anatomy Unit, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy.
  • 3 Center for Biomedical Informatics and Biostatistics, The University of Arizona Health Sciences, Tucson, AZ, USA.
  • 4 Department of Medicine, College of Medicine, The University of Arizona, Tucson, AZ, USA.
  • 5 Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, KU Leuven, B-3000, Leuven, Belgium.
  • 6 Genomics Core Leuven, Centre for Human Genetics KU Leuven, 3000, Leuven, Belgium.
  • 7 Facility for SYstems BIOlogy based MAss sepctrometry, KU Leuven, 3000, Leuven, Belgium.
  • 8 Center for Health Technologies (CHT), University of Pavia, Pavia, Italy.
  • 9 Translational Cell and Tissue Research Lab, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
  • 10 Department of Electrical, Computer and Biomedical Engineering, and Centre for Health Technologies (CHT), University of Pavia, Pavia, Italy.
  • 11 Department of Development and Regeneration, Stem Cell Institute, KU Leuven, B-3000, Leuven, Belgium. frederic.lluisvinas@kuleuven.be.
  • 12 Department of Development and Regeneration, Stem Cell Institute, KU Leuven, B-3000, Leuven, Belgium. maurilio.sampaolesi@kuleuven.be.
  • 13 Human Anatomy Unit, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy. maurilio.sampaolesi@kuleuven.be.
  • 14 Center for Health Technologies (CHT), University of Pavia, Pavia, Italy. maurilio.sampaolesi@kuleuven.be.
  • # Contributed equally.
PMID: 31654035 DOI: 10.1038/s41418-019-0433-3
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.

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