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Time-dependent appearance of myofibroblasts in granulation tissue of human skin wounds

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Summary

Human skin wounds (66) inflicted between 20 h and 7 months prior to biopsy were studied. In order to identify the type of cellular differentiation of the fibroblastic cells in the granulation tissue, alpha-smooth muscle actin and desmin were immunohistochemically localized. The value of any presumed time-dependent appearance and/or disappearance of positively stained cells was tested for the estimation of wound age. In skin specimens with a wound age less than 5 days (n =15) no typical granulation tissue had developed and no alpha-actin-positive myofibroblasts could be detected. The first appearance of positively reacting myofibroblasts was noted in a 5-day-old wound. In 57% of the lesions with a wound age between 5 and 31 days (25 out of 44 cases) typical granulation tissue formation was present and myofibroblasts with positive reaction for alpha-smooth muscle actin could be identified. Numerous positively reacting cells could generally be found in wounds aged between 16 and 31 days, but also in wounds less than 16 days old. In 29% of the cases with a wound age of more than 31 days (2 out of 7 cases) alpha-sma-positive myofibroblasts also occured. Fibroblastic cells positive for desmin could not be seen at all in our series. Our results demonstrate the appearance of alpha-sma-positive myofibroblasts with the initial formation of typical granulation tissue in human skin lesions as early as approximately 5 days after wounding. In contrast to recent experimental results these cells remained detectable in wounds aged more than 2 months in some cases. The immunohistochemical detection of actin-positive cells, therefore, demonstrates whether an unknown skin wound is aged approximately 5 days or more. Even though a time-dependent decrease of myofibroblasts in human granulation tissue after 31 days in human wounds seems probable, the extended presence (up to about 2 months) of these cells allows no further exact age determination of older wounds.

Zusammenfassung

Es wurden 66 menschliche Hautwunden mit einem Wundalter zwischen 20 Stunden und 7 Monaten sowie komplikationsloser Wundheilung ausgewertet. Nach immunhistochemischer Darstellung von alpha-Aktin und Desmin wurde das zeitabhängige Auftreten positiv reagierender Myofibroblasten im Wundgebiet untersucht. Es zeigte sich hierbei, daß in Hautwunden mit einem Wundalter unter 5 Tagen keine positiv anfärbbaren Zellen zu beobachten waren. In 57% (25 von 44 Fällen) der Hautverletzungen, die zwischen 5 und 31 Tagen überlebt worden waren, fanden sich im Granulationsgewebe alpha-Aktin haltige Myofibroblasten. Besonders zahlreiche, positiv reagierende Zellen traten zwischen ca. 16 bis 31 Tagen nach Wundsetzung auf, konnten jedoch auch bereits in Hautwunden jüngeren Alters beobachtet werden. In 2 von 7 Fällen mit einem Wundalter zwischen 1 und 7 Monaten (29%) liesen sich ebenfalls alpha-Aktin positive Myofibroblasten im Wundgebiet nachweisen. Desmin-haltige Myofibroblasten konnten nicht beobachtet werden. Die Ergebnisse zeigen, daß alpha-Aktin positive Myofibroblasten bereits mit Ausbildung typischen Granulationsgewebes ab ca. dem 5. Tag nach Verletzung im Wundgebiet auftreten. Der Nachweis positiv reagierender Zellen im Wundgebiet läßt jedoch aufgrund der Variabilität der Befunde keine weitere Differenzierung des Wundalters zu. Da alpha-Aktin-positive Myofibroblasten im Untersuchungsgut auch noch in einer Hautwunde mit einem Alter von 2 Monaten und 13 Tagen beobachtet werden konnten, ist die im Tierexperiment gefundene maximale Nachweisbarkeitsdauer von 30 Tagen auf das Granulationsgewebe menschlicher Hautwunden nicht übertragbar.

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This study was supported by a grant from the “Deutsche Forschungsgemeinschaft” (grant Ei 209/3-1) and by a grant from the “Friedrich-Baur-Stiftung”, University of Munich, FRG.

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Betz, P., Nerlich, A., Wilske, J. et al. Time-dependent appearance of myofibroblasts in granulation tissue of human skin wounds. Int J Leg Med 105, 99–103 (1992). https://doi.org/10.1007/BF02340832

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