Driving regeneration, instead of healing, in adult mammals: the decisive role of resident macrophages through efferocytosis

Tissue repair after lesion usually leads to scar healing and thus loss of function in adult mammals. In contrast, other adult vertebrates such as amphibians have the ability to regenerate and restore tissue homeostasis after lesion. Understanding the control of the repair outcome is thus a concernin...

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Published innpj Regenerative medicine Vol. 6; no. 1; p. 41
Main Authors Rabiller, Lise, Robert, Virginie, Arlat, Adèle, Labit, Elodie, Ousset, Marielle, Salon, Marie, Coste, Agnès, Da Costa-Fernandes, Léa, Monsarrat, Paul, Ségui, Bruno, André, Mireille, Guissard, Christophe, Renoud, Marie-Laure, Silva, Marine, Mithieux, Gilles, Raymond-Letron, Isabelle, Pénicaud, Luc, Lorsignol, Anne, Casteilla, Louis, Dromard Berthézène, Cécile, Cousin, Béatrice
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 03.08.2021
Nature Publishing Group
Springer Nature
Nature Portfolio
Subjects
631/250
631/443
631/80
Biomaterials
Biomedical and Life Sciences
Biomedicine
Cell Biology
Immunology
Life Sciences
Regenerative medicine
Regenerative Medicine/Tissue Engineering
Stem Cells
Tissue engineering
Cell biology
Physiology
Immunology
resident macrophages
efferocytosis
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Summary:Tissue repair after lesion usually leads to scar healing and thus loss of function in adult mammals. In contrast, other adult vertebrates such as amphibians have the ability to regenerate and restore tissue homeostasis after lesion. Understanding the control of the repair outcome is thus a concerning challenge for regenerative medicine. We recently developed a model of induced tissue regeneration in adult mice allowing the comparison of the early steps of regenerative and scar healing processes. By using studies of gain and loss of function, specific cell depletion approaches, and hematopoietic chimeras we demonstrate here that tissue regeneration in adult mammals depends on an early and transient peak of granulocyte producing reactive oxygen species and an efficient efferocytosis specifically by tissue-resident macrophages. These findings highlight key and early cellular pathways able to drive tissue repair towards regeneration in adult mammals.
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PMCID: PMC8333253
ISSN:2057-3995
2057-3995
DOI:10.1038/s41536-021-00151-1