Skip to main content

Advertisement

SpringerLink
Log in

Detection of fibrocytes in human skin wounds and its application for wound age determination

  • Original Article
  • Published:
International Journal of Legal Medicine Aims and scope Submit manuscript

Abstract

Fibrocytes, a newly identified cell type, are bone marrow-derived mesenchymal progenitors that coexpress hematopoietic cell antigens and fibroblast products. In this study, a double-color immunofluorescence analysis was carried out using anti-CD45 and anti-collagen type I antibodies to examine the time-dependent appearance of fibrocytes, using 53 human skin wounds with different wound ages (group I, 0–3 days; group II, 4–7 days; group III, 9–14 days; and group IV, 17–21 days). In wound specimens with an age of less than 3 days, CD45+/collagen type I+ fibrocytes were not detected. The fibrocytes were initially observed in wounds aged 4 days, and their number increased in lesions with advances in wound age. In a semiquantitative morphometrical analysis, the average number of fibrocytes was highest in the wounds of group III. These findings imply that human skin wounds containing fibrocytes are at least 4 days old. Moreover, a fibrocyte number of over 10 indicates a wound age between 9 and 14 days (i.e., group III). Based on the average number of fibrocytes in each group, a fibrocyte number of over 15 more strongly suggests a wound age of 9–14 days. Together, our observations indicate the participation of fibrocytes in wound healing of human skin inducing the accumulation of extracellular matrix components, and therefore, detection of fibrocytes could be a useful marker for wound age determination.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Laiho K (1998) Myeloperoxidase activity in skin lesions. I. Influence of the loss of blood, depth of excoriations and thickness of the skin. Int J Legal Med 111:6–9

    Article  PubMed  CAS  Google Scholar 

  2. Laiho K (1998) Myeloperoxidase activity in skin lesions. II. Influence of alcohol and some medicines. Int J Legal Med 111:10–12

    Article  PubMed  CAS  Google Scholar 

  3. Oehmichen M, Cropelin A (1995) Temporal course of intravital and postmortem proliferation of epidermal cells after mechanical injury. An immunohistochemical study using bromodeoxyuridine in rats. Int J Legal Med 107:257–262

    Article  PubMed  CAS  Google Scholar 

  4. Betz P (1994) Histological and enzyme histochemical parameters for the age estimation of human skin wounds. Int J Legal Med 107:60–68

    Article  PubMed  CAS  Google Scholar 

  5. Dressler J, Hanisch U, Kuhlisch E, Geiger KD (2007) Neuronal and glial apoptosis in human traumatic brain injury. Int J Legal Med 121:365–375

    Article  PubMed  CAS  Google Scholar 

  6. Eisenmenger W, Nerlich A, Glück G (1988) Die Bedeutung des Kollagens bei Wundaltersbestimmung. Z Rechtsmed 100:79–100

    Article  PubMed  CAS  Google Scholar 

  7. Betz P, Eisenmenger W (1996) Morphometrical analysis of hemosiderin deposits in relation to wound age. Int J Legal Med 108:262–264

    Article  PubMed  CAS  Google Scholar 

  8. Kondo T (2007) Timing of skin wounds. Leg Med (Tokyo) 9:109–114

    Google Scholar 

  9. Martin P (1997) Wound healing—aiming for perfect skin regeneration. Science 276:75–81

    Article  PubMed  CAS  Google Scholar 

  10. Singer AJ, Clark RA (1999) Cutaneous wound healing. N Engl J Med 341:738–746

    Article  PubMed  CAS  Google Scholar 

  11. Gillitzer R, Goebeler M (2001) Chemokines in cutaneous wound healing. J Leukoc Biol 69:513–521

    PubMed  CAS  Google Scholar 

  12. Martin P, Leibovich SJ (2005) Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol 15:599–607

    Article  PubMed  CAS  Google Scholar 

  13. Ishida Y, Gao JL, Murphy PM (2008) Chemokine receptor CX3CR1 mediates skin wound healing by promoting macrophage and fibroblast accumulation and function. J Immunol 180:569–579

    PubMed  CAS  Google Scholar 

  14. Ishida Y, Kimura A, Takayasu T, Eisenmenger W, Kondo T (2008) Expression of oxygen-regulated protein 150 (ORP150) in skin wound healing and its application for wound age determination. Int J Legal Med 122:409–414

    Article  PubMed  CAS  Google Scholar 

  15. Betz P, Nerlich A, Wilske J, Tubel J, Penning R, Eisenmenger W (1993) Analysis of the immunohistochemical localization of collagen type III and V for the time-estimation of human skin wounds. Int J Legal Med 105:329–332

    Article  PubMed  CAS  Google Scholar 

  16. Betz P, Nerlich A, Wilske J, Tubel J, Penning R, Eisenmenger W (1993) Immunohistochemical localization of collagen types I and VI in human skin wounds. Int J Legal Med 106:31–34

    Article  PubMed  CAS  Google Scholar 

  17. Betz P (1995) Immunohistochemical parameters for the age estimation of human skin wounds. A review. Am J Forensic Med Pathol 16:203–209

    Article  PubMed  CAS  Google Scholar 

  18. Betz P, Nerlich A, Tubel J, Wiest I, Hausmann R (1997) Detection of cell death in human skin wounds of various ages by an in situ end labeling of nuclear DNA fragments. Int J Legal Med 110:240–243

    Article  PubMed  CAS  Google Scholar 

  19. Dressler J, Bachmann L, Kasper M, Hauck JG, Muller E (1997) Time dependence of the expression of ICAM-1 (CD 54) in human skin wounds. Int J Legal Med 110:299–304

    Article  PubMed  CAS  Google Scholar 

  20. Dressler J, Bachmann L, Koch R, Muller E (1999) Estimation of wound age and VCAM-1 in human skin. Int J Legal Med 112:159–162

    Article  PubMed  CAS  Google Scholar 

  21. Kondo T, Ohshima T (1996) The dynamics of inflammatory cytokines in the healing process of mouse skin wound: a preliminary study for possible wound age determination. Int J Legal Med 108:231–236

    Article  PubMed  CAS  Google Scholar 

  22. Kondo T, Ohshima T, Eisenmenger W (1999) Immunohistochemical and morphometrical study on the temporal expression of interleukin-1α (IL-1α) in human skin wounds for forensic wound age determination. Int J Legal Med 112:249–252

    Article  PubMed  CAS  Google Scholar 

  23. Ohshima T, Sato Y (1998) Time-dependent expression of interleukin-10 (IL-10) mRNA during the early phase of skin wound healing as a possible indicator of wound vitality. Int J Legal Med 111:251–255

    Article  PubMed  CAS  Google Scholar 

  24. Guan DW, Ohshima T, Kondo T (2000) Immunohistochemical study on Fas and Fas ligand in skin wound healing. Histochem J 32:85–91

    Article  PubMed  CAS  Google Scholar 

  25. Sato Y, Ohshima T (2000) The expression of mRNA of proinflammatory cytokines during skin wound healing in mice: a preliminary study for forensic wound age estimation (II). Int J Legal Med 113:140–145

    Article  PubMed  CAS  Google Scholar 

  26. Rebolledo Godoy M, Rebolledo Godoy AP, Oehmichen M (2000) AgNORs during the process of wound healing. Time dependency as evaluated in vital and postmortem biopsy. Int J Legal Med 113:244–246

    Article  PubMed  CAS  Google Scholar 

  27. Hayashi T, Ishida Y, Kimura A, Takayasu T, Eisenmenger W, Kondo T (2004) Forensic application of VEGF expression to skin wound age determination. Int J Legal Med 118:320–325

    Article  PubMed  Google Scholar 

  28. Kondo T, Ohshima T, Mori R, Guan DW, Ohshima K, Eisenmenger W (2002) Immunohistochemical detection of chemokines in human skin wounds and its application to wound age determination. Int J Legal Med 116:87–91

    Article  PubMed  CAS  Google Scholar 

  29. Metz CN (2003) Fibrocytes: a unique cell population implicated in wound healing. Cell Mol Life Sci 60:1342–1350

    Article  PubMed  CAS  Google Scholar 

  30. 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

    PubMed  CAS  Google Scholar 

  31. Bellini A, Mattoli S (2007) The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses. Lab Invest 87:858–870

    Article  PubMed  CAS  Google Scholar 

  32. Gomperts BN, Strieter RM (2007) Fibrocytes in lung disease. J Leukoc Biol 82:449–456

    Article  PubMed  CAS  Google Scholar 

  33. Quan TE, Cowper S, Wu SP, Bockenstedt LK, Bucala R (2004) Circulating fibrocytes: collagen-secreting cells of the peripheral blood. Int J Biochem Cell Biol 36:598–606

    Article  PubMed  CAS  Google Scholar 

  34. Kisseleva T, Uchinami H, Feirt N, Quintana-Bustamante O, Segovia JC, Schwabe RF, Brenner DA (2006) Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis. J Hepatol 45:429–438

    Article  PubMed  CAS  Google Scholar 

  35. Chesney J, Metz C, Stavitsky AB, Bacher M, Bucala R (1998) Regulated production of type I collagen and inflammatory cytokines by peripheral blood fibrocytes. J Immunol 160:419–425

    PubMed  CAS  Google Scholar 

  36. Schmidt M, Sun G, Stacey MA, Mori L, Mattoli S (2003) Identification of circulating fibrocytes as precursors of bronchial myofibroblasts in asthma. J Immunol 171:380–389

    PubMed  CAS  Google Scholar 

  37. Phillips RJ, Burdick MD, Hong K, Lutz MA, Murray LA, Xue YY, Belperio JA, Keane MP, Strieter RM (2004) Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J Clin Invest 114:438–446

    PubMed  CAS  Google Scholar 

  38. Ishida Y, Kimura A, Kondo T, Hayashi T, Ueno M, Takakura N, Matsushima K, Mukaida N (2007) Essential roles of the CC chemokine ligand 3-CC chemokine receptor 5 axis in bleomycin-induced pulmonary fibrosis through regulation of macrophage and fibrocyte infiltration. Am J Pathol 170:843–854

    Article  PubMed  CAS  Google Scholar 

  39. Yang L, Scott PG, Giuffre J, Shankowsky HA, Ghahary A, Tredget EE (2002) Peripheral blood fibrocytes from burn patients: identification and quantification of fibrocytes in adherent cells cultured from peripheral blood mononuclear cells. Lab Invest 82:1183–1192

    PubMed  CAS  Google Scholar 

  40. Pilling D, Tucker NM, Gomer RH (2006) Aggregated IgG inhibits the differentiation of human fibrocytes. J Leukoc Biol 79:1242–1251

    Article  PubMed  CAS  Google Scholar 

  41. Wang JF, Jiao H, Stewart TL, Shankowsky HA, Scott PG, Tredget EE (2007) Fibrocytes from burn patients regulate the activities of fibroblasts. Wound Repair Regen 15:113–121

    Article  PubMed  Google Scholar 

  42. Ishida Y, Kondo T, Kimura A, Matsushima K, Mukaida N (2006) Absence of IL-1 receptor antagonist impaired wound healing along with aberrant NF-κB activation and a reciprocal suppression of TGF-β signal pathway. J Immunol 176:5598–5606

    PubMed  CAS  Google Scholar 

  43. Kondo T, Tanaka J, Ishida Y, Mori R, Takayasu T, Ohshima T (2002) Ubiquitin expression in skin wounds and its application to forensic wound age determination. Int J Legal Med 116:267–272

    Article  PubMed  CAS  Google Scholar 

  44. Furuichi K, Gao JL, Murphy PM (2006) Chemokine receptor CX3CR1 regulates renal interstitial fibrosis after ischemia-reperfusion injury. Am J Pathol 169:372–387

    Article  PubMed  CAS  Google Scholar 

  45. Betz P, Nerlich A, Wilske J, Tubel J, Penning R, Eisenmenger W (1992) Time-dependent appearance of myofibroblasts in granulation tissue of human skin wounds. Int J Legal Med 105:99–103

    Article  PubMed  CAS  Google Scholar 

  46. Betz P, Nerlich A, Wilske J, Tubel J, Wiest I, Penning R, Eisenmenger W (1992) Time-dependent pericellular expression of collagen type IV, laminin, and heparan sulfate proteoglycan in myofibroblasts. Int J Legal Med 105:169–172

    Article  PubMed  CAS  Google Scholar 

  47. Kondo T, Ohshima T, Sato Y, Mayama T, Eisenmenger W (2000) Immunohistochemical study on the expression of c-Fos and c-Jun in human skin wounds. Histochem J 32:509–514

    Article  PubMed  CAS  Google Scholar 

  48. Mori L, Bellini A, Stacey MA, Schmidt M, Mattoli S (2005) Fibrocytes contribute to the myofibroblast population in wounded skin and originate from the bone marrow. Exp Cell Res 304:81–90

    Article  PubMed  CAS  Google Scholar 

  49. Wang J, Jiao H, Stewart TL, Lyons MV, Shankowsky HA, Scott PG, Tredget EE (2007) Accelerated wound healing in leukocyte-specific, protein 1-deficient mouse is associated with increased infiltration of leukocytes and fibrocytes. J Leukoc Biol 82:1554–1563

    PubMed  CAS  Google Scholar 

  50. Betz P, Nerlich A, Wilske J, Tubel J, Wiest I, Penning R, Eisenmenger W (1992) The time-dependent rearrangement of the epithelial basement membrane in human skin wounds—immunohistochemical localization of collagen IV and VII. Int J Legal Med 105:93–97

    Article  PubMed  CAS  Google Scholar 

  51. Hartlapp I, Abe R, Saeed RW, Peng T, Voelter W, Bucala R, Metz CN (2001) Fibrocytes induce an angiogenic phenotype in cultured endothelial cells and promote angiogenesis in vivo. FASEB J 15:2215–2224

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was financially supported by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

Author information

Authors and Affiliations

  1. Department of Forensic Medicine, Wakayama Medical University, 811-1 Kimiidera, 641-8509, Wakayama, Japan

    Yuko Ishida, Akihiko Kimura & Toshikazu Kondo

  2. Department of Forensic and Social Environmental Medicine, Graduate School of Medical Science, Kanazawa University, 920-8640, Kanazawa, Japan

    Tatsunori Takayasu

  3. Institute of Legal Medicine, University of Munich, Nuβbaumstraβe 26, 80336, Munich, Germany

    Wolfgang Eisenmenger

Authors
  1. Yuko Ishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akihiko Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tatsunori Takayasu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wolfgang Eisenmenger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Toshikazu Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toshikazu Kondo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ishida, Y., Kimura, A., Takayasu, T. et al. Detection of fibrocytes in human skin wounds and its application for wound age determination. Int J Legal Med 123, 299–304 (2009). https://doi.org/10.1007/s00414-009-0320-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00414-009-0320-4

Keywords

Search

Navigation