The influence of CD26+ and CD26- fibroblasts on the regeneration of human dermo-epidermal skin substitutes

Sci Rep. 2022 Feb 4;12(1):1944. doi: 10.1038/s41598-022-05309-5.


CD26, also known as dipeptidyl peptidase IV (DPPIV), is a multifunctional transmembrane protein playing a significant role in the cutaneous wound healing processes in the mouse skin. However, only scarce data are available regarding the distribution and function of this protein in the human skin. Therefore, the aim of this study was to investigate the impact of CD26 deficiency in human primary fibroblasts on the regeneration of human tissue-engineered skin substitutes in vivo. Dermo-epidermal skin analogs, based on collagen type I hydrogels, were populated either with human CD26+ or CD26knockout fibroblasts and seeded with human epidermal keratinocytes. These skin substitutes were transplanted onto the back of immune-incompetent rodents. Three weeks post-transplantation, the grafts were excised and analyzed with respect to specific epidermal and dermal maturation markers. For the first time, we show here that the expression of CD26 protein in human dermis is age-dependent. Furthermore, we prove that CD26+ fibroblasts are more active in the production of extracellular matrix (ECM) both in vitro and in vivo and are necessary to achieve rapid epidermal and dermal homeostasis after transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Cell Communication*
  • Cell Proliferation*
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Coculture Techniques
  • Dipeptidyl Peptidase 4 / deficiency
  • Dipeptidyl Peptidase 4 / genetics
  • Dipeptidyl Peptidase 4 / metabolism*
  • Extracellular Matrix / metabolism
  • Female
  • Fibroblasts / enzymology
  • Fibroblasts / transplantation*
  • Heterografts
  • Humans
  • Infant
  • Keratinocytes / metabolism
  • Keratinocytes / transplantation*
  • Male
  • Rats
  • Rats, Nude
  • Regeneration*
  • Signal Transduction
  • Skin Transplantation*
  • Skin, Artificial*
  • Time Factors


  • DPP4 protein, human
  • Dipeptidyl Peptidase 4