An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA

Marco Demaria; Naoko Ohtani; Sameh A Youssef; Francis Rodier; Wendy Toussaint; James R Mitchell; Remi-Martin Laberge; Jan Vijg; Harry Van Steeg; Martijn E T Dollé; Jan H J Hoeijmakers; Alain de Bruin; Eiji Hara; Judith Campisi

doi:10.1016/j.devcel.2014.11.012

An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA

Marco Demaria, Naoko Ohtani, Sameh A Youssef, Francis Rodier, Wendy Toussaint, James R Mitchell, Remi-Martin Laberge, Jan Vijg, Harry Van Steeg, Martijn E T Dollé, Jan H J Hoeijmakers, Alain de Bruin, Eiji Hara, Judith Campisi

Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Cellular senescence suppresses cancer by halting the growth of premalignant cells, yet the accumulation of senescent cells is thought to drive age-related pathology through a senescence-associated secretory phenotype (SASP), the function of which is unclear. To understand the physiological role(s) of the complex senescent phenotype, we generated a mouse model in which senescent cells can be visualized and eliminated in living animals. We show that senescent fibroblasts and endothelial cells appear very early in response to a cutaneous wound, where they accelerate wound closure by inducing myofibroblast differentiation through the secretion of platelet-derived growth factor AA (PDGF-AA). In two mouse models, topical treatment of senescence-free wounds with recombinant PDGF-AA rescued the delayed wound closure and lack of myofibroblast differentiation. These findings define a beneficial role for the SASP in tissue repair and help to explain why the SASP evolved.

Original language	English
Pages (from-to)	722-733
Number of pages	12
Journal	Developmental Cell
Volume	31
Issue number	6
DOIs	https://doi.org/10.1016/j.devcel.2014.11.012
Publication status	Published - 22-Dec-2014

Keywords

Animals
Apoptosis
Cell Aging
Cell Differentiation
Endothelial Cells
Female
Fibroblasts
Luminescence
Male
Mesoderm
Mice
Mice, Transgenic
Myofibroblasts
Platelet-Derived Growth Factor
Transgenes
Wound Healing

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10.1016/j.devcel.2014.11.012

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Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R-M., Vijg, J., Van Steeg, H., Dollé, M. E. T., Hoeijmakers, J. H. J., de Bruin, A., Hara, E., & Campisi, J. (2014). An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Developmental Cell, 31(6), 722-733. https://doi.org/10.1016/j.devcel.2014.11.012

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title = "An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA",

abstract = "Cellular senescence suppresses cancer by halting the growth of premalignant cells, yet the accumulation of senescent cells is thought to drive age-related pathology through a senescence-associated secretory phenotype (SASP), the function of which is unclear. To understand the physiological role(s) of the complex senescent phenotype, we generated a mouse model in which senescent cells can be visualized and eliminated in living animals. We show that senescent fibroblasts and endothelial cells appear very early in response to a cutaneous wound, where they accelerate wound closure by inducing myofibroblast differentiation through the secretion of platelet-derived growth factor AA (PDGF-AA). In two mouse models, topical treatment of senescence-free wounds with recombinant PDGF-AA rescued the delayed wound closure and lack of myofibroblast differentiation. These findings define a beneficial role for the SASP in tissue repair and help to explain why the SASP evolved.",

keywords = "Animals, Apoptosis, Cell Aging, Cell Differentiation, Endothelial Cells, Female, Fibroblasts, Luminescence, Male, Mesoderm, Mice, Mice, Transgenic, Myofibroblasts, Platelet-Derived Growth Factor, Transgenes, Wound Healing",

author = "Marco Demaria and Naoko Ohtani and Youssef, {Sameh A} and Francis Rodier and Wendy Toussaint and Mitchell, {James R} and Remi-Martin Laberge and Jan Vijg and {Van Steeg}, Harry and Doll{\'e}, {Martijn E T} and Hoeijmakers, {Jan H J} and {de Bruin}, Alain and Eiji Hara and Judith Campisi",

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Demaria, M, Ohtani, N, Youssef, SA, Rodier, F, Toussaint, W, Mitchell, JR, Laberge, R-M, Vijg, J, Van Steeg, H, Dollé, MET, Hoeijmakers, JHJ, de Bruin, A, Hara, E & Campisi, J 2014, 'An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA', Developmental Cell, vol. 31, no. 6, pp. 722-733. https://doi.org/10.1016/j.devcel.2014.11.012

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AU - Ohtani, Naoko

AU - Youssef, Sameh A

AU - Rodier, Francis

AU - Toussaint, Wendy

AU - Mitchell, James R

AU - Laberge, Remi-Martin

AU - Vijg, Jan

AU - Van Steeg, Harry

AU - Dollé, Martijn E T

AU - Hoeijmakers, Jan H J

AU - de Bruin, Alain

AU - Hara, Eiji

AU - Campisi, Judith

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AB - Cellular senescence suppresses cancer by halting the growth of premalignant cells, yet the accumulation of senescent cells is thought to drive age-related pathology through a senescence-associated secretory phenotype (SASP), the function of which is unclear. To understand the physiological role(s) of the complex senescent phenotype, we generated a mouse model in which senescent cells can be visualized and eliminated in living animals. We show that senescent fibroblasts and endothelial cells appear very early in response to a cutaneous wound, where they accelerate wound closure by inducing myofibroblast differentiation through the secretion of platelet-derived growth factor AA (PDGF-AA). In two mouse models, topical treatment of senescence-free wounds with recombinant PDGF-AA rescued the delayed wound closure and lack of myofibroblast differentiation. These findings define a beneficial role for the SASP in tissue repair and help to explain why the SASP evolved.

KW - Animals

KW - Apoptosis

KW - Cell Aging

KW - Cell Differentiation

KW - Endothelial Cells

KW - Female

KW - Fibroblasts

KW - Luminescence

KW - Male

KW - Mesoderm

KW - Mice

KW - Mice, Transgenic

KW - Myofibroblasts

KW - Platelet-Derived Growth Factor

KW - Transgenes

KW - Wound Healing

U2 - 10.1016/j.devcel.2014.11.012

DO - 10.1016/j.devcel.2014.11.012

M3 - Article

C2 - 25499914

SN - 1534-5807

VL - 31

SP - 722

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JO - Developmental Cell

JF - Developmental Cell

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ER -