Autologous adipose-derived regenerative cell therapy modulates development of hypertrophic scarring in a red Duroc porcine model

Stem Cell Res Ther. 2017 Nov 15;8(1):261. doi: 10.1186/s13287-017-0704-1.

Abstract

Background: Effective prevention and treatment of hypertrophic scars (HTSs), a common consequence of deep-partial thickness injury, remain a significant clinical challenge. Previous studies from our group have shown that autologous adipose-derived regenerative cells (ADRCs) represent a promising approach to improve wound healing and, thereby, impact HTS development. The purpose of this study was to assess the influence of local delivery of ADRCs immediately following deep-partial thickness cutaneous injury on HTS development in the red Duroc (RD) porcine model.

Methods: Bilateral pairs of deep-partial thickness excisional wounds (2 mm depth; 58 cm2 area) were created using an electric dermatome on RD pigs (n = 12). Autologous ADRCs were isolated from the inguinal fat pad and then sprayed directly onto the wound at a dose of 0.25 × 106 viable cells/cm2. The paired contralateral wound received vehicle control. Wound healing and development of HTS were assessed over 6 months using digital imaging, quantitative measurement of skin hardness and pigmentation, and histology.

Results: Data showed that ADRC treatment led to reduced scar hyperpigmentation compared to control (p < 0.05). Using the Durometer, at 2 and 6 months post-injury, skin hardness was 10-20% lower in ADRCs-treated wounds compared to control vehicle (p < 0.05). A similar trend was observed with the skin fibrometer. ADRC treatment promoted more normal collagen organization, improvement in the number of rete ridges (p < 0.01), longer elastic fiber length (p < 0.01), and reduced hypervascularity (blood vessel density; p < 0.05). ADRC treatment was associated with modulation of IL-6 expression within the wound/scar with upregulation 2 weeks after injury (wound healing phase) and downregulation at 2 months (early scarring phase) post-treatment compared to control CONCLUSIONS: These findings support the potential therapeutic value of autologous ADRC administration for reduction of HTS development following deep-partial cutaneous injury.

Keywords: Adipose-derived regenerative cells; Hypertrophic scarring; Inflammation; Wound healing.

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / metabolism
  • Adipose Tissue / cytology
  • Adipose Tissue / physiology
  • Animals
  • Cell Transplantation / methods
  • Cell- and Tissue-Based Therapy / methods*
  • Cicatrix, Hypertrophic / pathology
  • Cicatrix, Hypertrophic / prevention & control*
  • Collagen / genetics
  • Collagen / metabolism
  • Collagen / ultrastructure
  • Elasticity
  • Female
  • Gene Expression
  • Hardness
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Neovascularization, Pathologic / prevention & control
  • Skin / injuries*
  • Skin Pigmentation / physiology
  • Surgical Wound / metabolism
  • Surgical Wound / pathology
  • Surgical Wound / therapy*
  • Swine
  • Transplantation, Autologous
  • Wound Healing / physiology*

Substances

  • Interleukin-6
  • Collagen