Cytoskeletal and Cytocontractile Features of Myofibroblasts

  • Giulio Gabbiani


Two phenomena play an essential role for the closing of an open wound: one is formation and contraction of granulation tissue, and the second is epithelialization, i.e. movement and replication of epithelial cells over the wounded area. Similar to placenta during pregnancy, granulation tissue is a new and temporary organ which disappears as soon as the wound is closed by epithelialization. The main functions of granulation tissue are: 1) synthesis of new connective tissue, and 2) production of a contractile movement which brings together the margins of the wound. Old experiments by Carrel1 had shown that this contractile force is produced within the granulation tissue itself. We have studied the morphologic, functional and pharmacological characteristics of fibroblasts under normal conditions and during wound healing or fibrocontractive diseases. Our results indicate that during wound healing and fibrocontractive diseases, fibroblasts assume several characteristics of smooth muscle cells. These modified fibroblasts or myofibroblasts probably play the key role in granulation tissue contraction or in pathological connective tissue retractions.


Granulation Tissue Normal Fibroblast Wound Contraction Antimyosin Antibody Ulation Tissue 
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  1. 1.
    Carrel A., Cicatrisation of wounds. I. The relation between the size of a wound and the rate of its cicatrisation, J. Exp. Med. 24:429 (1916).CrossRefGoogle Scholar
  2. 2.
    Ross R., The connective tissue fiber forming cell, in: “Treatise on Collagen”, Vol. 2, Part A, G.N. Ramachandran, ed., Academic Press, New York (1968).Google Scholar
  3. 3.
    Movat H. Z. and Fernando N. V. P., The fine structure of connective tissue. I. The fibroblast, Exp. Mol. Pathol., 1:509 (1962).CrossRefGoogle Scholar
  4. 4.
    Ross R., and Benditt E. P., Wound healing and collagen formation. Sequential changes in components of guinea pig skin wounds observed in the electron microscope, J. Biophys. Biochem. Cytol. 11:677 (1961).CrossRefGoogle Scholar
  5. 5.
    Palade G. E., A small particulate component of the cytoplasm, in: “Rantiers in Cytology”, L.P. Sandford, ed., Yale University Press, New Haven (1958).Google Scholar
  6. 6.
    Greenle T. K. and Ross R., The development of the rat flexor digital tendon. A fine structure study, J. Ultrastruct. Res. 18:354 (1967).CrossRefGoogle Scholar
  7. 7.
    Ross R. and Greenle T.K., Electron microscopy: attachment sites between connective tissue cells, Science 153:997 (1966).CrossRefGoogle Scholar
  8. 8.
    Trelstad R. L., Kang A. H., Igarashi S., and Gross J., Isolation of two distinct collagens from chick cartilage, Biochemistry 9:4993 (1970).CrossRefGoogle Scholar
  9. 9.
    Gabbiani G., Ryan G. B., and Majno G., Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction, Experientia 27:549 (1971).CrossRefGoogle Scholar
  10. 10.
    Gabbiani G., Chaponnier C., and Huttner I., Cytoplasmic filaments and gap junctions in epithelial cells and myofibroblasts during wound healing, J. Cell Biol. 76:561 (1978).CrossRefGoogle Scholar
  11. 11.
    Majno G., Gabbiani G., Hirschel B. J., Ryan G. B., and Statkov P. R., Contraction of granulation tissue in vitro: similarity to smooth muscle, Science 173:548 (1971).CrossRefGoogle Scholar
  12. 12.
    Ryan G. B., Cliff W. J., Gabbiani G., Irle C., Statkov P. R., and Majno G., Myofibroblasts in an avascular fibrous tissue, Lab. Invest. 29:197 (1973).Google Scholar
  13. 13.
    Ryan G. B., Cliff W. J., Gabbiani G., Irle C., Montandon D., Statkov P. R., and Majno G., Myofibroblasts in human granulation tissue, Hum. Pathol. 5:55 (1974).CrossRefGoogle Scholar
  14. 14.
    Laemmli U. K., Cleavage of structural proteins during the assembly of the head of bacteriophage T4, Nature 227:680 (1970).CrossRefGoogle Scholar
  15. 15.
    Gabbiani G., The myofibroblast: A key cell for wound healing and fibrocontractive diseases, Progr. Clin. Biol. Res. 54:182 (1981).Google Scholar
  16. 16.
    O’Farrel P. H., High resolution two-dimensional electrophoresis of proteins, J. Biol. Chem. 250:4007 (1975).Google Scholar
  17. 17.
    Gabbiani G, Schmid E., Winter S., Chaponnier C., de Chastonay C., Vandekerckhove J., Weber K., and Franke W. W., Vascular smooth muscle cells differ from other smooth muscle cells: predominance of vimentin filaments and a specific type actin, Proc. Natl. Acad. Sci., U.S.A. 78:298 (1981).CrossRefGoogle Scholar
  18. 18.
    Madden J. W., and Peacock E. E., Studies on the biology collagen during wound healing. III. Dynamic metabolism of scar collagen and remodelling of dermal wounds, Ann. Surg. 174: 511 (1971).CrossRefGoogle Scholar
  19. 19.
    Bailey A. J., Bazin S., and Delaunay A., Changes in the nature of the collagen during development and resorption of granulation tissue, Biochem., Biophys. Acta 328–383 (1973).Google Scholar
  20. 20.
    Hansen T. M., Collagen development in granulation tissue as compared with collagen of skin and aorta from injured and non-injured rats, Acta Path. Microbiol. Scand. A, 83:721 (1975).Google Scholar
  21. 21.
    Bailey A. J., Sims T. J., Le Lous M., and Bazin S., Collagen polymorphism in experimental granulation tissue, Biochem. Biophys. Res. Commun. 66:1160 (1975).CrossRefGoogle Scholar
  22. 22.
    Babbiani G., Le Lous M., Bailey A. J., Bazin S. and Delaunay A., Collagen and myofibroblasts of granulation tissue. A chemical, ultrastructural and immunologic study, Virchows Arch. (Cell Pathol) 21:133 (1976).Google Scholar
  23. 23.
    Bazin S., Le Lous M., Duance V. C., Sims T. J., Bailey A. J., Gabbiani G., D’Andiran G., Pizzolato G., Browski A., Nicoletis C., and Delaunay A., Biochemistry and histology of the connective tissue of Dupuytrenfs disease lesions, Eur. J. Clin. Invest. 10:9 (1980).Google Scholar
  24. 24.
    Narayanan A. S., Page R. C., and Kuzan F., Collagens synthesized in vitro by diploid fibroblasts obtained from chronically inflamed connective tissue, Lab. Invest. 39:61 (1978).Google Scholar
  25. 25.
    Vande Berg J. S., Rudoph R., and Woodward M., Comparative growth dynamics and morphology between cultured myofibroblasts from granulating wounds and dermal fibroblasts, Am. J. Pathol. 114:187 (1984).Google Scholar
  26. 26.
    Somers K. D., Dawson D. M., Wright G. L., Leffell M. S., Rowe J. J., Bluemink G. G., Vande Berg. J. S., Gleischman S. H., Devine C. J., and Horton C. E., Cell culture of Peyronie’s disease plaque and normal penile tissue, J. Urol. 127:585 (1982).Google Scholar
  27. 27.
    Azzarone B., Failly-Crepin C., Daya-Grosjean J., Chaponnier C., and Gabbiani G., Abnormal behavior of cultured fibroblasts from nodule and non-affected aponeurosis of Dupuytren’s disease, J. Cell. Physiol. 117:353 (1983).CrossRefGoogle Scholar
  28. 28.
    Gabbiani G., Hirschel B. J., Ryan G. B., Statkov P. R., and Majno G., Granulation tissue as a contractile organ. A Study of structure and function, J. Exp. Med. 135:719 (1972). CrossRefGoogle Scholar
  29. 29.
    Adelstein R. S., Conti M. A., Johnson G. S., and Pastan I., Isolation and characterization of myosin from cloned mouse fibroblasts, Proc. Natl. Acad. Sci. U.S.A. 69:3693 (1972).CrossRefGoogle Scholar
  30. 30.
    Bray D., and Thomas C., The actin consert of fibroblasts, Biochem. J. 147:221 (1975).Google Scholar
  31. 31.
    Gabbiani G., Majno G., and Ryan G. B., The fibroblast as a contractile cell: the myofibroblast, in: “Biology of Fibroblast”, E. Kulonen and J. Pikkarainen, eds., Academic Press, London (1973).Google Scholar
  32. 32.
    Lazarides E., and Weber K., Actin antibody: the specific visualization of actin filaments in non-muscle cells, Proc. Natl. Acad. Sci U.S.A. 71:2268 (1974).CrossRefGoogle Scholar
  33. 33.
    Painter R. G., Sheetz M., and Singer S. J., Detection and ultrastructural localization of human smooth muscle myosin-like molecules in human non-muscle cells by specific antibodies, Proc. Natl. Acad. Sci, U.S.A. 72:1359 (1975).CrossRefGoogle Scholar
  34. 34.
    Weber K., and Groeschel-Stewart U., Antibody to myosin: the specific visualization of myosin-containing filaments in non-muscle cells, Proc. Natl. Acad. Sci., U.S.A. 71: 4561 (1974).CrossRefGoogle Scholar
  35. 35.
    James D. W., and Taylor J. F., The stress developed by sheets of chick fibroblasts in vitro, Exp. Cell Res. 54:107 (1969).CrossRefGoogle Scholar
  36. 36.
    Ariyan S., Enriquez R., and Krizek T. J., Wound contraction and fibrocontractive disorders, Arch. Surg. 113:1034 (1978).Google Scholar
  37. 37.
    Baur P.S., Larson D. L., and Stacey T. R., The observation of myofibroblasts in hypertrophic scars, Surg. Gynecol. Obstet. 141:22 (1975).Google Scholar
  38. 38.
    Baur P.S., Parks D. H., and Larson D. L., The healing of burn wounds, Clin. Plast. Surg. 4:389 (1977).Google Scholar
  39. 39.
    Dabelsteen E., and Kremenak C. R., Demonstration of actin in the fibroblasts of healing palatal wounds, Plast. Reconstr. Surg. 62:429 (1978).CrossRefGoogle Scholar
  40. 40.
    Grimaud J. A., and Borojevic R., Myofibroblasts in hepatic schistosomal fibrosis, Experientia 33:890 (1977).CrossRefGoogle Scholar
  41. 41.
    Guber S., and Rudolph R., The myofibroblast, Surg. Gynecol. Obstet. 146:641 (1978).Google Scholar
  42. 42.
    Larson D. L., Abston S., Willis B., Linares H., Dobrkovsky M., Evans E. B., and Lewis S. R., Contracture and scar formation in the burn patient, Clin. Plast. Surg. 1:653 (1974).Google Scholar
  43. 43.
    Madden J. W., On “the contractile fibroblast”, Plast. Reconstr. Surg. 52:291 (1973).CrossRefGoogle Scholar
  44. 44.
    Peacock E. E., Wound contraction and scar contracture, Plast. Reconstr. Surg. 62:600 (1978).Google Scholar
  45. 45.
    Roland J., Fibroblaste et myofibroblaste dans le processus granulomateux, Ann. Anat. Pathol. 21:37 (1976).Google Scholar
  46. 46.
    Rudolph R., and Woodward M., Spatial orientation of microtubules in contractile fibroblasts in vivo, Anat. Ree. 191:169 (1978).CrossRefGoogle Scholar
  47. 47.
    Rudolph R., Guber S., Suzuki M., and Woodward M., The life cycle of the myofibroblast, Surg. Gynecol. Obstet. 145:389 (1977).Google Scholar
  48. 48.
    Rudolph R., McClure W. J., and Woodward M., Contractile fibro blasts in chronic alcoholic cirrhosis, Gastroenterol. 76: 704 (1979).Google Scholar
  49. 49.
    Zimman O. A., Robles J. M., and Lee J. C., The fibrous capsule around mammary implants: an investigation, Aest. Plast. Surg. 2:217 (1978).CrossRefGoogle Scholar
  50. 50.
    Benjamin S. P., Mercer R. D., and Hawk W. A., Myofibroblastic contraction in spontaneous regression of multiple congenital mesenchymal haematomas, Cancer 40:2343 (1977).CrossRefGoogle Scholar
  51. 51.
    Chiu H. F., and McFarlane R. M., Pathogenesis of Dupuytren’s contracture: a correlative clinical-pathological study, J. Hand Surg. 3:1 (1978).Google Scholar
  52. 52.
    Feiner H., and Kaye G. I., Ultrastructural evidence of myofibro blasts in circumscribed fibromatosis, Arch. Path. Lab. Med. 100:265 (1976).Google Scholar
  53. 53.
    Fisher E. R., Paulson J. D., and Gregorio R. M., The myofibro blasts nature of the uterine plexiform tumor, Arch. Pathol. Lab. Med. 102:477 (1978).Google Scholar
  54. 54.
    Gabbiani G., and Majno G., Dupuytren’s contracture: fibroblast contraction? An ultrastructural study, Am. J. Pathol. 66:131 (1972).Google Scholar
  55. 55.
    Gokel J. M., and Hubner G., Occurrence of myofibroblasts in the different phases of morbus Dupuytren (Dupuytren’s contracture), Beitr. Pathol. 161:166 (1977).Google Scholar
  56. 56.
    Hueston J. T., Hurley V. J. and Whittingham S., The contracting fibroblast as a clue to Dupuytren’s contracture, The Hand 8:10 (1976).CrossRefGoogle Scholar
  57. 57.
    Katenkamp D., and Stiller D., Cellular composition of the so called dermatofibroma (histiocytoma cutis), Virchows Arch. (Pathol. Anat.) 367:325 (1975).Google Scholar
  58. 58.
    Madden J. W., Carolson E. C., and Hines J., Presence of modified fibroblasts in ischemic contracture of the intrinsic musculature of the hand, Surg. Gynecol. Obstet. 140:509 (1975).Google Scholar
  59. 59.
    Schwarzlmuller B., and Hofstadter F., Fibromatose der Schilddrusenregion. Eine elektronenmikroskopische und enzym- histochemische studie, Virchows Arch. (Pathol. Anat.) 377: 145 (1978).Google Scholar
  60. 60.
    Weathers D. R., and Campbell W. G., Ultrastructure of the giant cell fibroma of the oral mucosa, Oral Surg. 38:550 (1974).CrossRefGoogle Scholar
  61. 61.
    Wirman J. A., Nodular fasciitis, a lesion of myofibroblasts. An ultrastrueturai study, Cancer 38:2378 (1976).Google Scholar
  62. 62.
    Bhathal P. S., Presence of modified fibroblasts in cirrhotic livers in man, Pathology 4:139 (1972).CrossRefGoogle Scholar
  63. 63.
    Rudolph R., McClure W. J., and Woodward M, Contractile fibroblasts in chronic alcoholic cirrhosis, Gastroenterol. 76:704 (1979).Google Scholar
  64. 64.
    Nagle R. B., Evans L. W., and Reynolds D. G., Contractility of renal cortex following complete ureteral obstruction, Proc. Soc. Exp. Biol. Med. 148:611 (1975).Google Scholar
  65. 65.
    Churg A. M., and Kahn L. B., Myofibroblasts and related cells in malignant fibrous and fibrohistiocytic tumors, Hum. Pathol. 8:205 (1977).CrossRefGoogle Scholar
  66. 66.
    Stiller D., and Katenkamp D., Cellular features in desmoid fibromatosis and well-differentiated fibrosarcomas. An electron microscopic study, Virchows Arch. (Pathol. Anat.) 369:155 (1975).Google Scholar
  67. 67.
    Vasudev K. S., Harris M., A sarcoma of myofibroblasts. An ultrastructural study, Arch. Pathol. Lab. Med. 102:185 (1978).Google Scholar
  68. 68.
    D’Andiran G., and Gabbiani G., A metastasizing sarcoma of the pleura composed of myofibroblasts, in: “Progress in Surgical Pathology”, Vol. II, C. M. Fenoglio and M. Wolff, eds., Masson Publishing U.S.A. Inc., New York (1980).Google Scholar
  69. 69.
    Pollard T. D., and Wihing R. R., Actin and myosin and cell movement, CRC Crit. Rev. Biochem. 2:1 (1974).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Giulio Gabbiani
    • 1
  1. 1.Department of PathologyUniversity of GenevaGeneva 4Switzerland

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