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Cellular mechanisms of skin repair in humans and other mammals

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Journal of Cell Communication and Signaling Aims and scope

Abstract

The increased incidence of non-healing skin wounds in developed societies has prompted tremendous research efforts on the complex process known as “wound healing”. Unfortunately, the weak relevance of modern wound healing research to human health continues to be a matter of concern. This review summarizes the current knowledge of the cellular mechanisms that mediate wound closure in the skin of humans and laboratory animals. The author highlights the anatomical singularities of human skin vs. the skin of other mammals commonly used for wound healing research (i.e. as mice, rats, rabbits, and pigs), and discusses the roles of stem cells, myofibroblasts, and the matrix environment in the repair process. The majority of this review focuses on reepithelialization and wound closure. Other aspects of wound healing (e.g. inflammation, fibrous healing) are referred to when relevant to the main topic. This review aims at providing the reader with a clear understanding of the similarities and differences that have been reported over the past 100 years between the healing of human wounds and that of other mammals.

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References

  • Abe R, Donnelly SC, Peng T, Bucala R, Metz CN (2001) Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J Immunol 166:7556–7562

    Article  CAS  PubMed  Google Scholar 

  • Arao H, Shimada T, Hagisawa S, Ferguson-Pell M (2013) Morphological characteristics of the human skin over posterior aspect of heel in the context of pressure ulcer development. J Tissue Viability 22:42–51

    Article  PubMed  Google Scholar 

  • Arey LB (1932) Certain basic principles of wound healing. Anat Rec 51:299–313

    Article  Google Scholar 

  • Argenbright LW, Forbes PD (1982) Erythema and skin blood content. Br J Dermatol 106:569–574

    Article  CAS  PubMed  Google Scholar 

  • Arwert EN, Hoste E, Watt FM (2012) Epithelial stem cells, wound healing and cancer. Nat Rev Cancer 12:170–180

    Article  CAS  PubMed  Google Scholar 

  • Bell E, Ivarsson B, Merrill C (1979) Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc Natl Acad Sci U S A 76:1274–1278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berry DP, Harding KG, Stanton MR, Jasani B, Ehrlich HP (1998) Human wound contraction: collagen organization, fibroblasts, and myofibroblasts. Plast Reconstr Surg 102:124–131, discussion 132–124

    Article  CAS  PubMed  Google Scholar 

  • Bigelman J, Mertz PM (2004) Human and swine models of epidermal wound healing. In: Rovee DT, Maibach HI (eds) The epidermis in wound healing. CRC Press, Boca Raton, pp 113–123

    Google Scholar 

  • Billingham RE, Russell PS (1956) Studies on wound healing, with special reference to the phenomenon of contracture in experimental wounds in rabbits’ skin. Ann Surg 144:961–981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bishop GH (1945) Regeneration after experimental removal of skin in man. Am J Anat 76:153–181

    Article  Google Scholar 

  • Blanpain C, Fuchs E (2014) Stem cell plasticity. Plasticity of epithelial stem cells in tissue regeneration. Science 344: 1242281

  • Bramble DM, Lieberman DE (2004) Endurance running and the evolution of homo. Nature 432:345–352

    Article  CAS  PubMed  Google Scholar 

  • Breuss JM, Gallo J, DeLisser HM, Klimanskaya IV, Folkesson HG, Pittet JF, Nishimura SL, Aldape K, Landers DV, Carpenter W, Gillett N, Sheppard D, Matthay MA, Albelda SM, Kramer RH, Pytela R (1995) Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling. J Cell Sci 108(Pt 6):2241–2251

    CAS  PubMed  Google Scholar 

  • Butterworth RJ (1992) The histology of human granulating wounds. M.D. Thesis # U053163. University of Leicester, UK

  • Carrel A, Hartmann A (1916) Cicatrization of wounds : I. The relation between the size of a wound and the rate of its cicatrization. J Exp Med 24:429–450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Castella LF, Buscemi L, Godbout C, Meister JJ, Hinz B (2010) A new lock-step mechanism of matrix remodelling based on subcellular contractile events. J Cell Sci 123:1751–1760

    Article  CAS  PubMed  Google Scholar 

  • Clark RAF (1985) Cutaneous tissue repair: basic biologic considerations. I. J Am Acad Dermatol 13:701–725

    Article  CAS  PubMed  Google Scholar 

  • Clark RAF (1988) Overview and general considerations of wound repair. In: Clark RAF, Henson PM, Henson PM (eds) The molecular and cellular biology of wound repair. Plenum Press, New York, pp 3–33

    Chapter  Google Scholar 

  • Clark RAF (1996) Wound repair: overview and general considerations. In: Clark RAF (ed) The molecular and cellular biology of wound repair, 2nd edn. Plenum Press, New York, pp 3–50

    Google Scholar 

  • Clark RA, Winn HJ, Dvorak HF, Colvin RB (1983) Fibronectin beneath reepithelializing epidermis in vivo: sources and significance. J Investig Dermatol 80(Suppl 1):26s–30s

    Article  CAS  Google Scholar 

  • Coulombe PA (1997) Towards a molecular definition of keratinocyte activation after acute injury to stratified epithelia. Biochem Biophys Res Commun 236:231–238

    Article  CAS  PubMed  Google Scholar 

  • Cui CY, Schlessinger D (2015) Eccrine sweat gland development and sweat secretion. Exp Dermatol 24:644–650

    Article  CAS  PubMed  Google Scholar 

  • Dabiri G, Damstetter E, Phillips T (2016) Choosing a wound dressing based on common wound characteristics. Adv Wound Care 5:32–41

    Article  Google Scholar 

  • Desmoulière A, Redard M, Darby I, Gabbiani G (1995) Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am J Pathol 146:56–66

    PubMed  PubMed Central  Google Scholar 

  • Dimick AR (1988) Delayed wound closure: indications and techniques. Ann Emerg Med 17:1303–1304

    Article  CAS  PubMed  Google Scholar 

  • Discher DE, Janmey P, Wang YL (2005) Tissue cells feel and respond to the stiffness of their substrate. Science 310:1139–1143

    Article  CAS  PubMed  Google Scholar 

  • Donati G, Watt FM (2015) Stem cell heterogeneity and plasticity in epithelia. Cell Stem Cell 16:465–476

    Article  CAS  PubMed  Google Scholar 

  • Driskell RR, Watt FM (2015) Understanding fibroblast heterogeneity in the skin. Trends Cell Biol 25:92–99

    Article  CAS  PubMed  Google Scholar 

  • Du Noüy PL (1916a) Cicatrization of wounds : Iii. The relation between the age of the patient, the area of the wound, and the index of cicatrization. J Exp Med 24:461–470

    Article  PubMed  PubMed Central  Google Scholar 

  • Du Noüy PL (1916b) Cicatrization of wounds : Ii. Mathematical expression of the curve representing cicatrization. J Exp Med 24:451–460

    Article  PubMed  PubMed Central  Google Scholar 

  • Duscher D, Barrera J, Wong VW, Maan ZN, Whittam AJ, Januszyk M, Gurtner GC (2016) Stem cells in wound healing: the future of regenerative medicine? A mini-review. Gerontology 62:216–225

    Article  CAS  PubMed  Google Scholar 

  • Dyson M, Young S, Pendle CL, Webster DF, Lang SM (1988) Comparison of the effects of moist and dry conditions on dermal repair. J Investig Dermatol 91:434–439

    Article  CAS  PubMed  Google Scholar 

  • Eaglstein WH, Davis SC, Mehle AL, Mertz PM (1988) Optimal use of an occlusive dressing to enhance healing. Effect of delayed application and early removal on wound healing. Arch Dermatol 124:392–395

    Article  CAS  PubMed  Google Scholar 

  • Elias PM, Goerke J, Friend DS (1977) Mammalian epidermal barrier layer lipids: composition and influence on structure. J Investig Dermatol 69:535–546

    Article  CAS  PubMed  Google Scholar 

  • Ennis WJ, Sui A, Bartholomew A (2013) Stem cells and healing: impact on inflammation. Adv Wound Care 2:369–378

    Article  Google Scholar 

  • Fagrell B (1984) Microcirculation of the skin. In: Mortillaro NA (ed) The physiology and pharmacology of the microcirculation, vol 2. Academic, New York, pp 133–180

    Chapter  Google Scholar 

  • Ferry LL, Argentieri G, Lochner DH (1995) The comparative histology of porcine and guinea pig skin with respect to iontophoretic drug delivery. Pharm Acta Helv 70:43–56

    Article  CAS  PubMed  Google Scholar 

  • Forage AV (1962) The effects of removing the epidermis from burnt skin. Lancet 2:690–693

    Article  CAS  PubMed  Google Scholar 

  • Forbes PD (1967) Radiation effects in swine. I. Vascular supply of the skin and hair. Usnrdl-tr-67-141. Res Dev Tech Rep: 1–18

  • Forbes PD, Urbach F (1969) Vascular and neoplastic changes in mice following ultraviolet radiation. In: Urbach F (ed) The biologic effects of ultraviolet radiation (with emphasis on the skin). Pergamon Press, Oxford, pp 279–289

    Google Scholar 

  • Freedberg IM, Tomic-Canic M, Komine M, Blumenberg M (2001) Keratins and the keratinocyte activation cycle. J Investig Dermatol 116:633–640

    Article  CAS  PubMed  Google Scholar 

  • Gabbiani G, Ryan GB, Majne G (1971) Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia 27:549–550

    Article  CAS  PubMed  Google Scholar 

  • Gabbiani G, Chaponnier C, Huttner I (1978) Cytoplasmic filaments and gap junctions in epithelial cells and myofibroblasts during wound healing. J Cell Biol 76:561–568

    Article  CAS  PubMed  Google Scholar 

  • Gharzi A, Reynolds AJ, Jahoda CA (2003) Plasticity of hair follicle dermal cells in wound healing and induction. Exp Dermatol 12:126–136

    Article  CAS  PubMed  Google Scholar 

  • Gibbins JR (1968) Migration of stratified squamous epithelium in vivo. The development of phagocytic ability. Am J Pathol 53:929–951

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gillman T, Penn J, Bronks D, Roux M (1955) A re-examination of certain aspects of the histogenesis of the healing of cutaneous wounds; a preliminary report. Br J Surg 43:141–153

    Article  CAS  PubMed  Google Scholar 

  • Gordillo GM, Bernatchez SF, Diegelmann R, Di Pietro LA, Eriksson E, Hinz B, Hopf HW, Kirsner R, Liu P, Parnell LK, Sandusky GE, Sen CK, Tomic-Canic M, Volk SW, Baird A (2013) Preclinical models of wound healing: is man the model? Proceedings of the wound healing society symposium. Adv Wound Care 2:1–4

    Article  Google Scholar 

  • Greenwood JE (2010) Function of the panniculus carnosus—a hypothesis. Vet Rec 167:760

    Article  PubMed  Google Scholar 

  • Grillo HC, Gross J (1967) Collagenolytic activity during mammalian wound repair. Dev Biol 15:300–317

    Article  CAS  PubMed  Google Scholar 

  • Gross J, Farinelli W, Sadow P, Anderson R, Bruns R (1995) On the mechanism of skin wound “contraction”: a granulation tissue “knockout” with a normal phenotype. Proc Natl Acad Sci U S A 92:5982–5986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haapasalmi K, Zhang K, Tonnesen M, Olerud J, Sheppard D, Salo T, Kramer R, Clark RA, Uitto VJ, Larjava H (1996) Keratinocytes in human wounds express alpha v beta 6 integrin. J Investig Dermatol 106:42–48

    Article  CAS  PubMed  Google Scholar 

  • Hadfield G (1963) The tissue of origin of the fibroblasts of granulation tissue. Br J Surg 50:870–881

    Article  CAS  PubMed  Google Scholar 

  • Hartwell SW Sr (1929) Surgical wounds in human beings: a histologic study of healing with practical applications: I. Epithelial healing. Arch Surg 19:835–847

    Article  Google Scholar 

  • Hartwell SW (1930) Surgical wounds in human beings: a Histologic study of healing with practical applications: Ii. Fibrous healing. Arch Surg 21:76–96

    Article  Google Scholar 

  • Hartwell SW, Sr. (1955) The mechanisms of healing in human wounds; a correlation of the clinical and tissue factors involved in the healing of human surgical wounds, burns, ulcers, and donor sites. Springfield, Ill.: Thomas. 166 p

  • Havran WL, Jameson JM (2010) Epidermal t cells and wound healing. J Immunol 184:5423–5428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Higton DI, James DW (1964) The force of contraction of full-thickness wounds of rabbit skin. Br J Surg 51:462–466

    Article  CAS  PubMed  Google Scholar 

  • Hinman CD, Maibach H (1963) Effect of air exposure and occlusion on experimental human skin wounds. Nature 200:377–378

    Article  CAS  PubMed  Google Scholar 

  • Hinz B (2010) The myofibroblast: paradigm for a mechanically active cell. J Biomech 43:146–155

    Article  PubMed  Google Scholar 

  • Hinz B, Mastrangelo D, Iselin CE, Chaponnier C, Gabbiani G (2001a) Mechanical tension controls granulation tissue contractile activity and myofibroblast differentiation. Am J Pathol 159:1009–1020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hinz B, Celetta G, Tomasek JJ, Gabbiani G, Chaponnier C (2001b) Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. Mol Biol Cell 12:2730–2741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hinz B, Phan SH, Thannickal VJ, Prunotto M, Desmouliere A, Varga J, De Wever O, Mareel M, Gabbiani G (2012) Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. Am J Pathol 180:1340–1355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Holyoke JB, Lobitz WC Jr (1952) Histologic variations in the structure of human eccrine sweat glands. J Investig Dermatol 18:147–167

    Article  CAS  PubMed  Google Scholar 

  • Hwang K, Baik SH (1997) Distribution of hairs and sweat glands on the bodies of Korean adults: a morphometric study. Acta Anat (Basel) 158:112–120

    Article  CAS  Google Scholar 

  • Inoue M, Kratz G, Haegerstrand A, Stahle-Backdahl M (1995) Collagenase expression is rapidly induced in wound-edge keratinocytes after acute injury in human skin, persists during healing, and stops at re-epithelialization. J Investig Dermatol 104:479–483

    Article  CAS  PubMed  Google Scholar 

  • Ito M, Liu Y, Yang Z, Nguyen J, Liang F, Morris RJ, Cotsarelis G (2005) Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nat Med 11:1351–1354

    Article  CAS  PubMed  Google Scholar 

  • Jahoda CA, Reynolds AJ (2001) Hair follicle dermal sheath cells: unsung participants in wound healing. Lancet 358:1445–1448

    Article  CAS  PubMed  Google Scholar 

  • Jensen KB, Watt FM (2006) Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence. Proc Natl Acad Sci U S A 103:11958–11963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jonkman MF (1989) Introduction, survey of the literature and aim of this study. In: Jonkman MF (ed) Epidermal wound healing between moist and dry: the enhancing effects of a new poly(ether urethane) wound covering on the reepithelialization of partial-thickness wounds. Rijksuniversiteit Groningen, Groningen, pp 13–30

    Google Scholar 

  • Larjava H, Salo T, Haapasalmi K, Kramer RH, Heino J (1993) Expression of integrins and basement membrane components by wound keratinocytes. J Clin Invest 92:1425–1435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Qiao L, Huang X, Yuan K, Yang H (2013) Clinical evaluation of polyurethane foam dressing on wound healing of skin graft donor site. Journal of Shanghai Jiaotong University. Med Sci 33:663–666

    Google Scholar 

  • Lobitz WC Jr, Holyoke JB, Montagna W (1954) Responses of the human eccrine sweat duct to controlled injury: growth center of the epidermal sweat duct unit. J Investig Dermatol 23:329–344

    Article  PubMed  Google Scholar 

  • Lu C, Fuchs E (2014) Sweat gland progenitors in development, homeostasis, and wound repair. Cold Spring Harb Perspect Med 4:

  • Lu S, Xiang J, Qing C, Jin S, Liao Z, Shi J (2002) Effect of necrotic tissue on progressive injury in deep partial thickness burn wounds. Chin Med J 115:323–325

    PubMed  Google Scholar 

  • Lu CP, Polak L, Rocha AS, Pasolli HA, Chen S-C, Sharma N, Blanpain C, Fuchs E (2012) Identification of stem cell populations in sweat glands and ducts reveals roles in homeostasis and wound repair. Cell 150:136–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mangelsdorf S, Vergou T, Sterry W, Lademann J, Patzelt A (2014) Comparative study of hair follicle morphology in eight mammalian species and humans. Skin Res Technol 20:147–154

    Article  PubMed  Google Scholar 

  • Marples MJ (1965) Cutaneous appendages: the sweat gland. In: The ecology of human skin. Charles C. Thomas, Springfield, pp 22–45

    Google Scholar 

  • Martin CW, Muir IF (1990) The role of lymphocytes in wound healing. Br J Plast Surg 43:655–662

    Article  CAS  PubMed  Google Scholar 

  • Maruthamuthu V, Sabass B, Schwarz US, Gardel ML (2011) Cell-ecm traction force modulates endogenous tension at cell-cell contacts. Proc Natl Acad Sci U S A 108:4708–4713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsumura H, Mohri Y, Binh NT, Morinaga H, Fukuda M, Ito M, Kurata S, Hoeijmakers J, Nishimura EK (2016) Hair follicle aging is driven by transepidermal elimination of stem cells via col17a1 proteolysis. Science 351: aad4395

  • Mehendale F, Martin P (2001) The molecular and cellular events of wound healing. In: Falanga V (ed) Cutaneous wound healing. Martin Dunitz Ltd, London, pp 15–38

    Google Scholar 

  • Meyer W (2009) Hair follicles in domesticated mammals with comparison to laboratory animals and humans. In: Mecklenburg L, Linek M, Tobin DJ (eds) Hair loss disorders in domestic animals. Wiley-Blackwell, Ames, pp 43–64

    Google Scholar 

  • Miller SJ, Burke EM, Rader MD, Coulombe PA, Lavker RM (1998) Re-epithelialization of porcine skin by the sweat apparatus. J Investig Dermatol 110:13–19

    Article  CAS  PubMed  Google Scholar 

  • Montagna W (1967) Comparative anatomy and physiology of the skin. Arch Dermatol 96:357–363

    Article  CAS  PubMed  Google Scholar 

  • Montagna W (1972) The skin of nonhuman primates. Am Zool 12:109–124

    Article  Google Scholar 

  • Montagna W (1977) Morphology of cutaneous sensory receptors. J Investig Dermatol 69:4–7

    Article  CAS  PubMed  Google Scholar 

  • Montagna W (1984a) Embryology and anatomy of the cutaneous adnexa. J Cutan Pathol 11:350–351

    Article  CAS  PubMed  Google Scholar 

  • Montagna W (1984b) Some particularities of human skin and the skin of nonhuman primates. G Ital Dermatol Venereol 119:1–4

    CAS  PubMed  Google Scholar 

  • Montagna W, Yun JS (1964) The skin of the domestic pig. J Investig Dermatol 42:11–21

    Article  CAS  PubMed  Google Scholar 

  • Morimoto Y, Saga K (1995) Proliferating cells in human eccrine and apocrine sweat glands. J Histochem Cytochem 43:1217–1221

    Article  CAS  PubMed  Google Scholar 

  • Nowak JA, Polak L, Pasolli HA, Fuchs E (2008) Hair follicle stem cells are specified and function in early skin morphogenesis. Cell Stem Cell 3:33–43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Odland G, Ross R (1968) Human wound repair. I Epidermal regeneration. J Cell Biol 39:135–151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohyama M, Terunuma A, Tock CL, Radonovich MF, Pise-Masison CA, Hopping SB, Brady JN, Udey MC, Vogel JC (2006) Characterization and isolation of stem cell-enriched human hair follicle bulge cells. J Clin Invest 116:249–260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ortonne JP, Loning T, Schmitt D, Thivolet J (1981) Immunomorphological and ultrastructural aspects of keratinocyte migration in epidermal wound healing. Virchows Arch A Pathol Anat Histopathol 392:217–230

    Article  CAS  Google Scholar 

  • Page ME, Lombard P, Ng F, Gottgens B, Jensen KB (2013) The epidermis comprises autonomous compartments maintained by distinct stem cell populations. Cell Stem Cell 13:471–482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pailler-Mattei C, Debret R, Vargiolu R, Sommer P, Zahouani H (2013) In vivo skin biophysical behaviour and surface topography as a function of ageing. J Mech Behav Biomed Mater 28:474–483

    Article  CAS  PubMed  Google Scholar 

  • Poblet E, Jimenez-Acosta F, Rocamora A (1994) Qbend/10 (anti-cd34 antibody) in external root sheath cells and follicular tumors. J Cutan Pathol 21:224–228

    Article  CAS  PubMed  Google Scholar 

  • Rea TH Jr (1968) The anatomic site of vascular injury in mouse skin exposed to ultraviolet light. J Investig Dermatol 51:100–107

    Article  PubMed  Google Scholar 

  • Rendell MS, McIntyre SF, Terando JV, Kelly ST, Finney DA (1993) Skin blood flow in the wistar-kyoto rat and the spontaneously hypertensive rat. Comp Biochem Physiol A 106:349–354

    Article  CAS  Google Scholar 

  • Richardson GD, Arnott EC, Whitehouse CJ, Lawrence CM, Reynolds AJ, Hole N, Jahoda CA (2005) Plasticity of rodent and human hair follicle dermal cells: implications for cell therapy and tissue engineering. J Investig Dermatol Symp Proc 10:180–183

    Article  PubMed  Google Scholar 

  • Rinkevich Y, Walmsley GG, Hu MS, Maan ZN, Newman AM, Drukker M, Januszyk M, Krampitz GW, Gurtner GC, Lorenz HP, Weissman IL, Longaker MT (2015) Identification and isolation of a dermal lineage with intrinsic fibrogenic potential. Science 348: aaa2151

  • Rittié L (2015) Another dimension to the importance of the extracellular matrix in fibrosis. J Cell Commun Signal 9:99–100

    Article  PubMed  PubMed Central  Google Scholar 

  • Rittié L, Fisher GJ (2015) Natural and sun-induced aging of human skin. Cold Spring Harb Perspect Med 5:a015370

    Article  PubMed  Google Scholar 

  • Rittié L, Stoll SW, Kang S, Voorhees JJ, Fisher GJ (2009) Hedgehog signaling maintains hair follicle stem cell phenotype in young and aged human skin. Aging Cell 8:738–751

    Article  PubMed  CAS  Google Scholar 

  • Rittié L, Sachs DL, Orringer JS, Voorhees JJ, Fisher GJ (2013a) Eccrine sweat glands are major contributors to reepithelialization of human wounds. Am J Pathol 182:163–171

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rittié L, Orringer JS, Sachs DL, Voorhees JJ, Fisher GJ (2013b) Eccrine sweat gland-derived keratinocytes rapidly express epidermal differentiation markers during repair of human wounds. J Investig Dermatol 133:S251

    Google Scholar 

  • Rittié L, Farr EA, Orringer JS, Voorhees JJ, Fisher GJ (2016) Reduced cell cohesiveness of outgrowths from eccrine sweat glands delays wound closure in elderly skin. Aging Cell accepted:

  • Rompolas P, Mesa KR, Greco V (2013) Spatial organization within a niche as a determinant of stem-cell fate. Nature 502:513–518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ryan GB, Cliff WJ, Gabbiani G, Irle C, Montandon D, Statkov PR, Majno G (1974) Myofibroblasts in human granulation tissue. Hum Pathol 5:55–67

    Article  CAS  PubMed  Google Scholar 

  • Saarialho-Kere UK, Kovacs SO, Pentland AP, Olerud JE, Welgus HG, Parks WC (1993) Cell-matrix interactions modulate interstitial collagenase expression by human keratinocytes actively involved in wound healing. J Clin Invest 92:2858–2866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saga K (2002) Structure and function of human sweat glands studied with histochemistry and cytochemistry. Prog Histochem Cytochem 37:323–386

    Article  CAS  PubMed  Google Scholar 

  • Sato K, Sato F (1983) Individual variations in structure and function of human eccrine sweat gland. Am J Physiol 245:R203–R208

    CAS  PubMed  Google Scholar 

  • Sato K, Kang WH, Saga K, Sato KT (1989) Biology of sweat glands and their disorders. Ii Disorders of sweat gland function. J Am Acad Dermatol 20:713–726

    Article  CAS  PubMed  Google Scholar 

  • Semer NB, Adler-Lavan M (2001) Skin grafts. In: NSemer B, Adler-Lavan M (eds) Practical plastic surgery for nonsurgeons. Hanley & Belfus, Philadelphia, pp 97–109

    Google Scholar 

  • Sinclair R, Chapman A, Magee J (2005) The lack of significant changes in scalp hair follicle density with advancing age. Br J Dermatol 152:646–649

    Article  CAS  PubMed  Google Scholar 

  • Siver A, Montagna W, Karacan I (1964) Age and sex differences in spontaneous, adrenergic and cholinergic human sweating. J Investig Dermatol 43:255–265

    Article  CAS  PubMed  Google Scholar 

  • Snowden JM, Kennedy DF, Cliff WJ (1982) Wound contraction. The effects of scab formation and the nature of the wound bed. Aust J Exp Biol Med Sci 60:73–82

    Article  CAS  PubMed  Google Scholar 

  • Stanley JR, Alvarez OM, Bere EW Jr, Eaglstein WH, Katz SI (1981) Detection of basement membrane zone antigens during epidermal wound healing in pigs. J Investig Dermatol 77:240–243

    Article  CAS  PubMed  Google Scholar 

  • Stenn KS, Paus R (2001) Controls of hair follicle cycling. Physiol Rev 81:449–494

    CAS  PubMed  Google Scholar 

  • Su Y, Richmond A (2015) Chemokine regulation of neutrophil infiltration of skin wounds. Adv Wound Care 4:631–640

    Article  Google Scholar 

  • Suga H, Rennert RC, Rodrigues M, Sorkin M, Glotzbach JP, Januszyk M, Fujiwara T, Longaker MT, Gurtner GC (2014) Tracking the elusive fibrocyte: identification and characterization of collagen-producing hematopoietic lineage cells during murine wound healing. Stem Cells 32:1347–1360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sullivan TP, Eaglstein WH, Davis SC, Mertz P (2001) The pig as a model for human wound healing. Wound Repair Regen 9:66–76

    Article  CAS  PubMed  Google Scholar 

  • Szabo G (1967) The regional anatomy of the human integument with special reference to the distribution of hair follicles, sweat glands and melanocytes. Philos Trans R Soc Lond B 252:447–485

    Article  Google Scholar 

  • Taylor G, Lehrer MS, Jensen PJ, Sun TT, Lavker RM (2000) Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell 102:451–461

    Article  CAS  PubMed  Google Scholar 

  • Tiwari VK (2012) Burn wound: How it differs from other wounds? Indian J Plast Surg 45:364–373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA (2002) Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 3:349–363

    Article  CAS  PubMed  Google Scholar 

  • Turcan I, Jonkman MF (2015) Blistering disease: insight from the hemidesmosome and other components of the dermal-epidermal junction. Cell Tissue Res 360:545–569

    Article  CAS  PubMed  Google Scholar 

  • Van Winkle W Jr (1968) The epithelium in wound healing. Surg Gynecol Obstet 127:1089–1115

    PubMed  Google Scholar 

  • Vardaxis NJ, Brans TA, Boon ME, Kreis RW, Marres LM (1997) Confocal laser scanning microscopy of porcine skin: implications for human wound healing studies. J Anat 190(Pt 4):601–611

    Article  PubMed  PubMed Central  Google Scholar 

  • Viziam CB, Matoltsy AG, Mescon H (1964) Epithelialization of small wounds. J Investig Dermatol 43:499–507

    Article  CAS  PubMed  Google Scholar 

  • Wagner KJ (1964) Epithelial regeneration in anesthetic areas after spinal cord injuries. Plast Reconstr Surg 34:268–274

    Article  CAS  PubMed  Google Scholar 

  • Watts GT, Grillo HC, Gross J (1958) Studies in wound healing: Ii. The role of granulation tissue in contraction. Ann Surg 148:153–160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weiss P (1961) The biological foundations of wound repair. Harvey Lect 55:13–42

    CAS  PubMed  Google Scholar 

  • Welch MP, Odland GF, Clark RAF (1990) Temporal relationships of f-actin bundle formation, collagen and fibronectin matrix assembly, and fibronectin receptor expression to wound contraction. J Cell Biol 110:133–145

    Article  CAS  PubMed  Google Scholar 

  • Williams MG, Hunter R (1957) Studies on epidermal regeneration by means of the strip method. J Investig Dermatol 29:407–413

    Article  CAS  PubMed  Google Scholar 

  • Winstanley EW (1975) The epithelial reaction in the healing of excised cutaneous wounds in the dog. J Comp Pathol 85:61–75

    Article  CAS  PubMed  Google Scholar 

  • Winter GD (1962) Formation of the scab and the rate of epithelization of superficial wounds in the skin of the young domestic pig. Nature 193:293–294

    Article  CAS  PubMed  Google Scholar 

  • Winter GD (1971) Healing of skin wounds and the influence of dressings on the repair process. In: Harkiss KJ (ed) Surgical dressings and wound healing: proceedings of a symposium held on 7–8 July 1970 at the university of Bradford. Crosby Lockwood [for] Bradford University Press, London, pp 46–60

    Google Scholar 

  • Winter GD (1972) Epidermal regeneration studied in the domestic pig. In: Maibach HI, Rovee DT (eds) Epidermal wound healing. Year Book Medical Publishers, Chicago, pp 71–112

    Google Scholar 

  • Woodley DT, Briggaman RA (1988) Re-formation of the epidermal-dermal junction during wound healing. In: Clark RAF, Henson PM (eds) The molecular and cellular biology of wound repair. Plenum Press, New York, pp 559–586

    Chapter  Google Scholar 

  • Wu Y, Wang J, Scott PG, Tredget EE (2007) Bone marrow-derived stem cells in wound healing: a review. Wound Repair Regen 15:S18–S26

    Article  PubMed  Google Scholar 

  • Zahir M (1965) Formation of scabs on skin wounds. Br J Surg 52:376–380

    Article  CAS  PubMed  Google Scholar 

  • Zhao M, Song B, Pu J, Forrester JV, McCaig CD (2003) Direct visualization of a stratified epithelium reveals that wounds heal by unified sliding of cell sheets. FASEB J 17:397–406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The author acknowledges all the published work that was not cited because of space limitations. She also thanks the librarians at the University of Michigan for their tremendous help with retrieving the older (and newer) documents cited herein.

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Correspondence to Laure Rittié.

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Rittié, L. Cellular mechanisms of skin repair in humans and other mammals. J. Cell Commun. Signal. 10, 103–120 (2016). https://doi.org/10.1007/s12079-016-0330-1

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