Cell therapy based on adipose tissue-derived stromal cells promotes physiological and pathological wound healing

Arterioscler Thromb Vasc Biol. 2009 Apr;29(4):503-10. doi: 10.1161/ATVBAHA.108.178962. Epub 2009 Feb 5.

Abstract

Objective: We hypothesized that adipose tissue may contain progenitors cells with cutaneous and angiogenic potential.

Methods and results: Adipose tissue-derived stroma cells (ADSCs) were administrated to skin punched wounds of both nonirradiated and irradiated mice (20 Gy, locally). At day 14, ADSCs promoted dermal wound healing and enhanced wound closure, viscolesticity, and collagen tissue secretion in both irradiated and nonirradiated mice. Interestingly, GFP-positive ADSCs incorporated in dermal and epidermal tissue in vivo and expressed epidermal markers K5 and K14. Cultured ADSCs in keratinocyte medium have been shown to differentiate into K5- and K14-positive cells and produced high levels of KGF. At Day 7, ADSCs also improved skin blood perfusion assessed by laser Doppler imaging, capillary density, and VEGF plasma levels in both irradiated and nonirradiated animals. GFP-positive ADSCs incorporated into capillary structures in vivo and expressed the endothelial cell marker CD31. Finally, in situ interphase fluorescence hybridization showed that a small number of ADSCs have the potential to fuse with endogenous keratinocytes.

Conclusions: ADSCs participate in dermal wound healing in physiological and pathological conditions by their ability to promote reepithelialization and angiogenesis. Hence, adipose lineage cells represent a new cell source for therapeutic dermal wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism
  • Adipose Tissue / transplantation*
  • Animals
  • Capillaries / metabolism
  • Cell Differentiation
  • Cell Fusion
  • Cell Lineage
  • Cell Transplantation*
  • Cells, Cultured
  • Dermatologic Surgical Procedures*
  • Endothelial Cells / metabolism
  • Endothelial Cells / transplantation*
  • Fibroblast Growth Factor 7 / metabolism
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Keratinocytes / metabolism
  • Keratinocytes / transplantation*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Neovascularization, Physiologic
  • Regional Blood Flow
  • Skin / blood supply
  • Skin / physiopathology
  • Skin / radiation effects
  • Stromal Cells / metabolism
  • Stromal Cells / transplantation*
  • Time Factors
  • Vascular Endothelial Growth Factor A / blood
  • Wound Healing*

Substances

  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 7
  • Green Fluorescent Proteins