TY - JOUR
T1 - Autologous micrograft accelerates endogenous wound healing response through ERK-induced cell migration
AU - Balli, Martina
AU - Vitali, Francesca
AU - Janiszewski, Adrian
AU - Caluwé, Ellen
AU - Cortés-Calabuig, Alvaro
AU - Carpentier, Sebastien
AU - Duelen, Robin
AU - Ronzoni, Flavio
AU - Marcelis, Lukas
AU - Bosisio, Francesca Maria
AU - Bellazzi, Riccardo
AU - Luttun, Aernout
AU - De Angelis, Maria G.Cusella
AU - Ceccarelli, Gabriele
AU - Lluis, Frederic
AU - Sampaolesi, Maurilio
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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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U2 - 10.1038/s41418-019-0433-3
DO - 10.1038/s41418-019-0433-3
M3 - Article
C2 - 31654035
AN - SCOPUS:85074570919
SN - 1350-9047
VL - 27
SP - 1520
EP - 1538
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 5
ER -