Exogenous peripheral blood mononuclear cells affect the healing process of deep‑degree burns

Mol Med Rep. 2017 Dec;16(6):8110-8122. doi: 10.3892/mmr.2017.7672. Epub 2017 Sep 29.

Abstract

The regenerative repair of deep‑degree (second degree) burned skin remains a notable challenge in the treatment of burn injury, despite improvements being made with regards to treatment modality and the emergence of novel therapies. Fetal skin constitutes an attractive target for investigating scarless healing of burned skin. To investigate the inflammatory response during scarless healing of burned fetal skin, the present study developed a nude mouse model, which was implanted with normal human fetal skin and burned fetal skin. Subsequently, human peripheral blood mononuclear cells (PBMCs) were used to treat the nude mouse model carrying the burned fetal skin. The expression levels of matrix metalloproteinase (MMP)‑9 and tissue inhibitor of metalloproteinases (TIMP)‑1 were investigated during this process. In the present study, fetal skin was subcutaneously implanted into the nude mice to establish the murine model. Hematoxylin and eosin staining was used to detect alterations in the skin during the development of fetal skin and during the healing process of deep‑degree burned fetal skin. The expression levels of MMP‑9 and TIMP‑1 were determined using immunochemical staining, and their staining intensity was evaluated by mean optical density. The results demonstrated that fetal skin subcutaneously implanted into the dorsal skin flap of nude mice developed similarly to the normal growth process in the womb. In addition, the scarless healing process was clearly observed in the mice carrying the burned fetal skin. A total of 2 weeks was required to complete scarless healing. Following treatment with PBMCs, the burned fetal skin generated inflammatory factors and enhanced the inflammatory response, which consequently resulted in a reduction in the speed of healing and in the formation of scars. Therefore, exogenous PBMCs may alter the lowered immune response environment, which is required for scarless healing, resulting in scar formation. In conclusion, the present study indicated that the involvement of inflammatory cells is important during the healing process of deep‑degree burned skin, and MMP‑9 and TIMP‑1 may serve important roles in the process of scar formation.

MeSH terms

  • Adult
  • Animals
  • Burns / diagnosis
  • Burns / genetics
  • Burns / immunology
  • Burns / metabolism*
  • Cicatrix / metabolism
  • Cicatrix / pathology
  • Disease Models, Animal
  • Humans
  • Leukocytes, Mononuclear / physiology*
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Regeneration
  • Skin / metabolism
  • Skin / pathology
  • Skin Transplantation
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Wound Healing*
  • Young Adult

Substances

  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinase 9