Abstract
Repair of damaged dermal tissue is accomplished by dynamic cell-cell and cell-matrix interactions involving activation of resident cells as well as cells that migrate into the lesion. Immediately after injury there is a hemostatic response that activates platelets. Platelets release transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF), which begin the recruitment of inflammatory cells and activate several resident dermal cell types. The most notable early inflammatory response is the infiltration of neutrophils. These are necessary to control infection and begin clearing the damaged tissue but are not critical to the healing process. Wound healing begins a few days later with the infiltration of monocyte/macrophages at the site. These cells release a number of cyotokines, synthesize extracellular matrix (ECM), and serve as a source of stem cells. The ECM becomes vascularized by angiogenesis and forms granulation tissue. Neovascularization is accomplished using both resident endothelial cells and circulating progenitor cells from the blood. Scar formation proceeds with the activation, migration, and proliferation of fibroblasts and the formation of a three-dimensional scaffold of ECM. A hematologically derived monocyte/stem cell may be the major contributor to early matrix synthesis. These blood-derived stem cells are able to produce a wide variety of proinflammatory cytokines (IL-1β, TNF-α, MIP-1α, MIP-1β, PDGF-A and TGF-β), which make major contributions to the healing process. Contraction of the wound is driven by activation and differentiation of mesenchymal cells into myofibroblasts that are able to draw the edges of the damaged tissue over the deficit. Migration of viable keratinocytes within the wound and from the edges of it stimulated by types I and IV collagen, fibronectin and vitronectin, as well as serum factors is responsible for reepithelialization of the surface. The cells include both the basal stem cells of the epidermis and the transit-amplifying cells. If epidermal stem cells are lost, migrating stem cells from surviving hair follicles are able to supply epidermal cells.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Abe, R., Donnelly, S. C., Peng, T., Bucala, R., and Metz, C. N. (2001) Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J. Immunol. 166:7556–7562.
Bucala, R., Spiegel, L. A., Chesney, J., Hogan, M., and Cerami, A. (1994) Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol. Med. 1:71–81.
Carmeliet, P. and Luttun, A. (2001) The emerging role of the bone marrow-derived stem cells in (therapeutic) angiogenesis. Thromb. Haemost. 86:289–297.
Chen-Kiang, S., Cardinale, G. J., and Udenfriend, S. (1977) Expression of collagen biosynthetic activities in lymphocytic cells. Proc. Natl. Acad. Sci. USA 75:1379–1383.
Chesney, J., Metz C., Stavitsky, A. B., Bacher, M., and Bucala, R. (1998) Regulated production of type I collagen and inflammatory cytokines by peripheral blood fibrocytes. J. Immunol. 160:419–425.
Clark, R. A. F. (1996) Overview of wound repair. In: The Molecular and Cellular Biology of Wound Repair (Clark, R. A. F., ed.), Plenum, New York, pp. 3–50.
Clark, R. A. F., Lanigan, J. M., DellaPelle, P., Manseau, E., Dvorak, H. F. and Colvin, R. B. (1982) Fibronecin and fibrin provide a provisional matrix for epidermal cell migration during wound reepithelialization. J. Invest. Dermatol. 79:264–269.
Cohen, I. K., Diegelmann, R. F., and Lindblad, W. J., eds. (1992) Wound Healing: Biochemical and Clinical Aspects, Saunders, Philadelphia, PA.
Cohnheim, J. (1867) Ueber entzundung und eiterung. Virchows Arch. 40:1.
Desmoulière, A., Redard, M., Darby, I., and Gabbiani, G. (1995) Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am. J. Pathol. 146:56–66.
Dunphy, J. E. and Upuda, K. N. (1955) Chemical and histochemical sequences in the normal healing of wounds. N. Engl. J. Med. 253: 847–851.
Gabbiani, G., Ryan, G. B., and Majno, G. (1971) Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia 27:549–550.
Gillman, T. and Wright, L. J. (1966) Autoradiographic evidence suggesting in vivo transformation of some blood mononuclears in repair and fibrosis. Nature 209:1086–1090.
Goldberg, B. and Green, H. (1968) The synthesis of collagen and protocollagen hydroxylase by fibroblastic and nonfibroblastic cell lines. Pathology 59:1110–1116.
Graham, M. F., Diegelmann, R. F., Lindblad, W. J., Gay, S., Gay, R., and Cohen, I. K. (1984) Effects of inflammation on wound healing: in vitro studies and in vivo studies. In: Soft and Hard Tissue Repair: Biological and Clinical Aspects (Hunt, T. K., Heppenstall, R. B., Pines, E., Rovee, D., eds.), Praeger Scientific, New York, pp. 361–379.
Gross, J. (1996) Getting to mammalian wound repair and amphibian limb regeneration: A mechanistic link in the early events. Wound Rep. Reg. 4:190–202.
Jang, Y.-C., Arumugam S., Gibran, N. S., and Isik, F. F. (1999) Role of αv integrins and angiogenesis during wound repair. Wound Rep. Reg. 7:375–380.
Jensen, U., Lowell, S., and Watt, F. M. (1999) The spatial relationship between stem cells and their progeny in the basal layer of human epidermis: a new view based on whole-mount labeling and lineage analysis. Development 126:2409–2418.
Jones, P. H. and Watt, F. M. (1993) Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell 73:713–724.
Jones, P. H., Harper, S., and Watt, F. M. (1995) Stem cell patterning and fate in human epidermis. Cell 80:83–93.
Leibovich, S. J. and Ross, R. (1975) The role of the macrophage in wound repair: a study with hydrocortisone and antimacrophage serum. Am. J. Pathol. 78:71–100.
Lindblad, W. J., French, J. A., Redford, K. S., Buenaventura, S. K., and Cohen, I. K. (1987) Induction of prolyl hydroxylase activity in a nonadherent population of human leukocytes. Biochem. Biophys. Res. Commun. 147:486–493.
Lindblad, W. J. (1998) Collagen expression by novel cell populations in the dermal wound environment. Wound Rep. Reg. 6:186–193.
Madri, J. A. and Bell, L. (1992) Vascular cell responses to injury: Modulation by extracellular matrix and soluble factors. In: Ultrastructure, Membranes and Cell Interactions in Atherosclerosis (Robenek, H. and Severs, N., eds.), CRC, Boca Raton, FL, pp. 167–181.
Mast, B. A. and Schultz, G. S. (1996) Interactions of cytokines, growth factors, and proteases in acute and chronic wounds. Wound Rep. Reg. 4:411–420.
Metchnikoff, E. (1893) Lectures on the Comparative Pathology of Inflammation, Keegan, Paul, and Trubner, London, UK.
Myllyla, R. and Seppa, H. (1979) Studies on the enzymes of collagen biosynthesis and the synthesis of hydroxyproline in macrophages and mast cells. Biochem. J. 182:311–316.
Odland, G. and Ross, R. (1968) Human wound repair. I. Epidermal regeneration. J. Cell Biol. 39:135–151.
Oshima, H., Rochat, A., Kedzia, C., Kobayashi, K., and Barrandon, Y. (2001) Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell 104:233–245.
Rappolee, D. A., Mark, D., Banda, M. J., and Werb, Z. (1988) Wound macrophages express TGF-α and other growth factors in vivo: analysis by mRNA phenotyping. Science 241:708–712.
Reyes, M., Dudek, A., Jahagirdar, B., Koodie, L., Marker, P. H., and Verfaillie, C. M. (2002) Origin of endothelial progenitors in human postnatal bone marrow. J. Clin. Invest. 109:337–315.
Roberts, A. B., (1995) Transforming growth factor-β: activity and efficacy in animal models of wound healing. Wound Rep. Reg. 3: 408–418.
Rochat, A., Kobayashi, K., and Barrandon, Y. (1994) Location of stem cells of human hair follicles by clonal analysis. Cell 76:1063–1073.
Rogers, A. A., Burnett, S., Moore, J. C., Shakespeare, P. G., and Chen, W. Y. J. (1995) Involvement of proteolytic enzymes (plasminogen activators and matrix metalloproteinases) in the pathophysiology of pressure ulcers. Wound Rep. Reg. 3:273–283.
Ross, R., Everett, N. B., and Tyler, R. (1970) Wound healing and collagen formation. VI. The origin of the wound fibroblast studied in parabiosis. J. Cell Biol. 44:645–654.
Savill, J. (1997) Apoptosis in the resolution of inflammation. J. Leukoc. Biol. 61:375–380.
Shelton, E., and Rice, M. E. (1959) Growth of normal peritoneal cells in diffusion chambers: a study in cell modulation. Am. J. Anat. 105: 281–303.
Simpson, D. M. and Ross, R. (1972) The neutrophilic leukocyte in wound repair: a study with antineutrophil serum. J. Clin. Invest. 51: 2009–2023.
Squier, M. K., Sehnert, A. J., and Cohen, J. J. (1995) Apoptosis in leukocytes. J. Leukoc. Biol. 57:2–10.
Stenn, K. S. and Dvoretzky, I. (1979) Human serum and epithelial spread in tissue culture. Arch. Dermatol. Res. 246:3–15.
Vaage, J. and Lindblad, W. J. (1990) Production of collagen type I by mouse peritoneal macrophages. J. Leukoc. Biol. 48:274–280.
Woodley, D. T., Wynn, K. C., and O’Keefe, E. J. (1990) Type IV collagen and fibronectin enhance human keratinocyte thymidine incorporation. J. Invest. Dermatol. 94:139–143.
Yager, D. R. and Nwomeh, B. C. (1999) The proteolytic environment of chronic wounds. Wound Rep. Reg. 7:433–441.
Yamada, K. M. and Clark, R. A. F. (1996) Provisional matrix. In: The Molecular and Cellular Biology of Wound Repair (Clark, R. A. F., ed.), Plenum, New York, pp. 51–94.
Zhai Y., Vaage, J., and Lindblad, W. J. (1996) Expression of type I procollagen by cultured mouse peritoneal macrophages detected by in situ hybridization and immunohistochemical staining. Wound Rep. Reg. 4:185 (abstract).
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Springer Science+Business Media New York
About this chapter
Cite this chapter
Lindblad, W.J. (2004). Stem Cells in Dermal Wound Healing. In: Sell, S. (eds) Stem Cells Handbook. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-411-5_9
Download citation
DOI: https://doi.org/10.1007/978-1-59259-411-5_9
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-367-1
Online ISBN: 978-1-59259-411-5
eBook Packages: Springer Book Archive