Wound repair: a showcase for cell plasticity and migration.

A skin wound requires several cell lineages to exhibit considerable plasticity as they migrate towards and over the site of damage to contribute to repair. The keratinocytes that re-epithelialize the tissue, the dermal fibroblasts and potentially other mesenchymal stem cell populations that repopulate damaged connective tissue, the immune cells that counter infections, and endothelial cells that re-establish blood supply and facilitate the immune response - all of these cells are 'dynamic' in that they are activated by immediate wound cues, they reprogram to adopt cell behaviours essential for repair including migration, and finally they must resolve. In adult tissues, repair is unique in its requirement for dramatic cell changes and movements otherwise associated only with development and disease.

[1]  I. Helfrich,et al.  A wound size-dependent effect of myeloid cell-derived vascular endothelial growth factor on wound healing. , 2011, The Journal of investigative dermatology.

[2]  V. Kadirkamanathan,et al.  A Zebrafish Compound Screen Reveals Modulation of Neutrophil Reverse Migration as an Anti-Inflammatory Mechanism , 2014, Science Translational Medicine.

[3]  S. Mckercher,et al.  Wound Healing in the PU.1 Null Mouse—Tissue Repair Is Not Dependent on Inflammatory Cells , 2003, Current Biology.

[4]  A. Huttenlocher,et al.  Lyn is a redox sensor that mediates leukocyte wound attraction in vivo , 2011, Nature.

[5]  L. Ryan,et al.  Cellular sources and inducers of cytokines present in acute wound fluid , 2011, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[6]  Albrecht Schwab,et al.  Directional Cell Migration and Chemotaxis in Wound Healing Response to PDGF-AA are Coordinated by the Primary Cilium in Fibroblasts , 2010, Cellular Physiology and Biochemistry.

[7]  B. Ju,et al.  Histone H3K27 Demethylase JMJD3 in Cooperation with NF-κB Regulates Keratinocyte Wound Healing. , 2016, The Journal of investigative dermatology.

[8]  A. Desmoulière,et al.  Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. , 1995, The American journal of pathology.

[9]  A. Joyner,et al.  Nerve-derived sonic hedgehog defines a niche for hair follicle stem cells capable of becoming epidermal stem cells. , 2011, Cell stem cell.

[10]  S. Werner,et al.  A Glutathione-Nrf2-Thioredoxin Cross-Talk Ensures Keratinocyte Survival and Efficient Wound Repair , 2016, PLoS genetics.

[11]  R. Ross,et al.  The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. , 1975, The American journal of pathology.

[12]  D. Prockop Marrow Stromal Cells as Stem Cells for Nonhematopoietic Tissues , 1997, Science.

[13]  Wei Li,et al.  Extracellular heat shock protein‐90α: linking hypoxia to skin cell motility and wound healing , 2007, The EMBO journal.

[14]  L. Bruckner-Tuderman,et al.  Collagen VII plays a dual role in wound healing. , 2013, The Journal of clinical investigation.

[15]  R. Medzhitov,et al.  Tissue-Specific Signals Control Reversible Program of Localization and Functional Polarization of Macrophages , 2014, Cell.

[16]  Ash A. Alizadeh,et al.  Gene Expression Signature of Fibroblast Serum Response Predicts Human Cancer Progression: Similarities between Tumors and Wounds , 2004, PLoS biology.

[17]  FeisstVaughan,et al.  Characterization of mesenchymal progenitor cell populations directly derived from human dermis. , 2014 .

[18]  A. Brooks,et al.  Characterization of mesenchymal progenitor cell populations directly derived from human dermis. , 2014, Stem cells and development.

[19]  B. Hinz,et al.  The nano-scale mechanical properties of the extracellular matrix regulate dermal fibroblast function. , 2014, The Journal of investigative dermatology.

[20]  E. Fuchs,et al.  A Role for Skin γδ T Cells in Wound Repair , 2002, Science.

[21]  Allon M. Klein,et al.  Interfollicular Epidermal Stem Cells Self-Renew via Autocrine Wnt Signaling , 2013, Science.

[22]  Ichiro Ono,et al.  The mechanisms underlying fibroblast apoptosis regulated by growth factors during wound healing , 2010, The Journal of pathology.

[23]  W. Parks,et al.  Induction and Repression of Collagenase-1 by Keratinocytes Is Controlled by Distinct Components of Different Extracellular Matrix Compartments* , 1997, The Journal of Biological Chemistry.

[24]  H. Pasolli,et al.  Identification of Stem Cell Populations in Sweat Glands and Ducts Reveals Roles in Homeostasis and Wound Repair , 2012, Cell.

[25]  F. Watt,et al.  Integrin expression by human epidermal keratinocytes can be modulated by interferon-γ, transforming growth factor-β, tumor necrosis factor-α, and culture on a dermal equivalent , 1995 .

[26]  C. Nobes,et al.  An early molecular component of the wound healing response in rat embryos—induction of c-fos protein in cells at the epidermal wound margin , 1992, Mechanisms of Development.

[27]  T. Lecuit,et al.  Actomyosin networks and tissue morphogenesis , 2014, Development.

[28]  Paul Martin,et al.  Calcium Flashes Orchestrate the Wound Inflammatory Response through DUOX Activation and Hydrogen Peroxide Release , 2013, Current Biology.

[29]  Werner Müller,et al.  Differential Roles of Macrophages in Diverse Phases of Skin Repair , 2010, The Journal of Immunology.

[30]  R. Paus,et al.  Hair Follicle Bulge Stem Cells Appear Dispensable for the Acute Phase of Wound Re‐epithelialization , 2016, Stem cells.

[31]  S. O'Kane,et al.  Scar-free healing: from embryonic mechanisms to adult therapeutic intervention. , 2004, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[32]  H. Shimizu,et al.  Mesenchymal Stem Cells Are Recruited into Wounded Skin and Contribute to Wound Repair by Transdifferentiation into Multiple Skin Cell Type1 , 2008, The Journal of Immunology.

[33]  W. Bloch,et al.  Interleukin-4 Receptor α Signaling in Myeloid Cells Controls Collagen Fibril Assembly in Skin Repair. , 2015, Immunity.

[34]  N. Gibran,et al.  Mesenchymal stem cells induce dermal fibroblast responses to injury. , 2010, Experimental cell research.

[35]  Paul Martin,et al.  Prioritization of Competing Damage and Developmental Signals by Migrating Macrophages in the Drosophila Embryo , 2010, Current Biology.

[36]  T. Shaw,et al.  Histone deacetylase 2 is upregulated in normal and keloid scars. , 2012, The Journal of investigative dermatology.

[37]  L. Hudson,et al.  Developmental transcription factor slug is required for effective re‐epithelialization by adult keratinocytes , 2005, Journal of cellular physiology.

[38]  R. Bucala,et al.  Peripheral Blood Fibrocytes: Differentiation Pathway and Migration to Wound Sites1 , 2001, The Journal of Immunology.

[39]  F. Watt,et al.  Aberrant integrin expression during epidermal wound healing and in psoriatic epidermis. , 1992, The Journal of clinical investigation.

[40]  J. Albina,et al.  The Monocyte to Macrophage Transition in the Murine Sterile Wound , 2014, PloS one.

[41]  Qingfeng Li,et al.  Identification of biomechanical force as a novel inducer of epithelial-mesenchymal transition features in mechanical stretched skin. , 2015, American journal of translational research.

[42]  J. Albina,et al.  The phenotype of murine wound macrophages , 2010, Journal of leukocyte biology.

[43]  C. Glass,et al.  Molecular control of activation and priming in macrophages , 2015, Nature Immunology.

[44]  B. Ebert,et al.  Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis. , 2015, Cell stem cell.

[45]  Timothy J. Mitchison,et al.  A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish , 2009, Nature.

[46]  G. Gabbiani,et al.  Alpha-smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. , 1990, Laboratory investigation; a journal of technical methods and pathology.

[47]  F. Ellett,et al.  Defining the phenotype of neutrophils following reverse migration in zebrafish , 2015, Journal of leukocyte biology.

[48]  G. Natoli,et al.  Transcriptional regulation of macrophage polarization: enabling diversity with identity , 2011, Nature Reviews Immunology.

[49]  R. Clark,et al.  Fibrinogen and fibrin are anti-adhesive for keratinocytes: a mechanism for fibrin eschar slough during wound repair. , 2001, The Journal of investigative dermatology.

[50]  Paul Martin,et al.  Wound healing and inflammation genes revealed by array analysis of 'macrophageless' PU.1 null mice , 2004, Genome Biology.

[51]  Santosh A. Khedkar,et al.  RhoB controls coordination of adult angiogenesis and lymphangiogenesis following injury by regulating VEZF1-mediated transcription , 2013, Nature Communications.

[52]  C. Pullar,et al.  ATP Release and P2Y Receptor Signaling are Essential for Keratinocyte Galvanotaxis , 2016, Journal of cellular physiology.

[53]  A. Sonnenberg,et al.  Integrin α3β1 inhibits directional migration and wound re-epithelialization in the skin , 2009, Journal of Cell Science.

[54]  M. Nieto Epithelial Plasticity: A Common Theme in Embryonic and Cancer Cells , 2013, Science.

[55]  Hiroyuki Miyoshi,et al.  The Role of Stromal Stem Cells in Tissue Regeneration and Wound Repair , 2009, Science.

[56]  K. Khosrotehrani,et al.  In Vivo Imaging Reveals a Pioneer Wave of Monocyte Recruitment into Mouse Skin Wounds , 2014, PloS one.

[57]  P. Kubes,et al.  Resolution Mediator Chemerin15 Reprograms the Wound Microenvironment to Promote Repair and Reduce Scarring , 2014, Current Biology.

[58]  J. Pollard,et al.  Macrophage Wnt-Calcineurin-Flt1 signaling regulates mouse wound angiogenesis and repair. , 2013, Blood.

[59]  W. Jiang,et al.  Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization , 2015, Cell reports.

[60]  G. Cotsarelis,et al.  Epithelial stem cells and implications for wound repair. , 2012, Seminars in cell & developmental biology.

[61]  Christian Moritz,et al.  Long-range Ca2+ waves transmit brain-damage signals to microglia. , 2012, Developmental cell.

[62]  K. Khosrotehrani,et al.  Correction: In Vivo Imaging Reveals a Pioneer Wave of Monocyte Recruitment into Mouse Skin Wounds , 2014, PLoS ONE.

[63]  P. Kubes,et al.  Intravascular Danger Signals Guide Neutrophils to Sites of Sterile Inflammation , 2010, Science.

[64]  D. Kaplan,et al.  Sox2-Mediated Regulation of Adult Neural Crest Precursors and Skin Repair , 2013, Stem cell reports.

[65]  M. Tomic-Canic,et al.  Keratins and the keratinocyte activation cycle. , 2001, The Journal of investigative dermatology.

[66]  S. Gordon,et al.  Macrophage recruitment during limb development and wound healing in the embryonic and foetal mouse. , 1994, Journal of cell science.

[67]  William J. Zuercher,et al.  Serum and Glucocorticoid–Regulated Kinase 1 Regulates Neutrophil Clearance during Inflammation Resolution , 2014, The Journal of Immunology.

[68]  Christiana Ruhrberg,et al.  Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. , 2010, Blood.

[69]  Paul G Scott,et al.  Mesenchymal Stem Cells Enhance Wound Healing Through Differentiation and Angiogenesis , 2007, Stem cells.

[70]  Janice L. Walker,et al.  Cells activated for wound repair have the potential to direct collective invasion of an epithelium , 2016, Molecular biology of the cell.

[71]  Paul Martin,et al.  Epigenetic reprogramming during wound healing: loss of polycomb‐mediated silencing may enable upregulation of repair genes , 2009, EMBO reports.

[72]  F. Watt,et al.  Epidermal β-catenin activation remodels the dermis via paracrine signalling to distinct fibroblast lineages , 2016, Nature Communications.

[73]  R. Bucala,et al.  Circulating Fibrocytes Define a New Leukocyte Subpopulation That Mediates Tissue Repair , 1994, Molecular medicine.

[74]  B. Hinz,et al.  Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. , 2001, Molecular biology of the cell.

[75]  V. Castronovo,et al.  Histone deacetylase 4 is required for TGFbeta1-induced myofibroblastic differentiation. , 2007, Biochimica et biophysica acta.

[76]  A. Hayday,et al.  The Intraepithelial T Cell Response to NKG2D-Ligands Links Lymphoid Stress Surveillance to Atopy , 2011, Science.

[77]  G. King,et al.  PKCδ inhibition normalizes the wound-healing capacity of diabetic human fibroblasts. , 2016, The Journal of clinical investigation.

[78]  Paul Martin,et al.  Corpse Engulfment Generates a Molecular Memory that Primes the Macrophage Inflammatory Response , 2016, Cell.

[79]  E. Tredget,et al.  Toll‐like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring , 2011, Journal of cellular physiology.

[80]  A. Zychlinsky,et al.  Neutrophil Extracellular Traps Kill Bacteria , 2004, Science.

[81]  Philipp J. Keller,et al.  Direct In Vivo Manipulation and Imaging of Calcium Transients in Neutrophils Identify a Critical Role for Leading-Edge Calcium Flux. , 2015, Cell reports.

[82]  B. King,et al.  Comparative transcriptomic profiling of hydrogen peroxide signaling networks in zebrafish and human keratinocytes: Implications toward conservation, migration and wound healing , 2016, Scientific Reports.

[83]  Paul Martin,et al.  Recapitulation of morphogenetic cell shape changes enables wound re-epithelialisation , 2014, Development.

[84]  Paul Martin,et al.  Immediate early genes krox‐24 and krox‐20 are rapidly up‐regulated after wounding in the embryonic and adult mouse , 2002, Developmental dynamics : an official publication of the American Association of Anatomists.

[85]  Fiona M. Watt,et al.  Distinct fibroblast lineages determine dermal architecture in skin development and repair , 2013, Nature.

[86]  T. Sutherland,et al.  Host protective roles of type 2 immunity: Parasite killing and tissue repair, flip sides of the same coin , 2014, Seminars in immunology.

[87]  T. Shaw,et al.  Molecular mechanisms linking wound inflammation and fibrosis: knockdown of osteopontin leads to rapid repair and reduced scarring , 2008, The Journal of experimental medicine.