Targeted delivery of adipose-derived stem cells via acellular dermal matrix enhances wound repair in diabetic rats

Authors

  • Chunlei Nie,

    1. Department of Head and Neck Surgery, Third Affiliated Hospital of Harbin Medical University, People's Republic of China
    2. Tissue Repair and Engineering Laboratory, Harbin Medical University, People's Republic of China
    Search for more papers by this author
    • These authors contributed equally to this study.

  • Guoyou Zhang,

    1. Department of Dermatology, University of Lübeck, Germany
    2. Department of Hand and Plastic Surgery, Second Affiliated Hospital of Wenzhou Medical College, Zhejiang, People's Republic of China
    Search for more papers by this author
    • These authors contributed equally to this study.

  • Daping Yang,

    1. Tissue Repair and Engineering Laboratory, Harbin Medical University, People's Republic of China
    2. Department of Plastic Surgery, Second Affiliated Hospital of Harbin Medical University, People's Republic of China
    Search for more papers by this author
  • Tong Liu,

    1. Department of Head and Neck Surgery, Third Affiliated Hospital of Harbin Medical University, People's Republic of China
    Search for more papers by this author
  • Dan Liu,

    1. Department of Plastic Surgery, Second Affiliated Hospital of Harbin Medical University, People's Republic of China
    Search for more papers by this author
  • Jin Xu,

    Corresponding author
    1. Department of Cell Biology, Harbin Medical University, People's Republic of China
    • Correspondence to: Jiewu Zhang, Department of Head and Neck Surgery, Third Affiliated Hospital of Harbin Medical University, 150 Ha Ping Road, Harbin 150040, People's Republic of China. E-mail: Jiewu_zhang@yahoo.com.cn or Jin Xu, Department of Cell Biology, Harbin Medical University. E-mail: xujinyd@sohu.com

    Search for more papers by this author
  • Jiewu Zhang

    Corresponding author
    1. Department of Head and Neck Surgery, Third Affiliated Hospital of Harbin Medical University, People's Republic of China
    • Correspondence to: Jiewu Zhang, Department of Head and Neck Surgery, Third Affiliated Hospital of Harbin Medical University, 150 Ha Ping Road, Harbin 150040, People's Republic of China. E-mail: Jiewu_zhang@yahoo.com.cn or Jin Xu, Department of Cell Biology, Harbin Medical University. E-mail: xujinyd@sohu.com

    Search for more papers by this author

Abstract

Cell-based therapeutic intervention has emerged as a new approach to accelerate wound closure. Adipose-derived stem cells (ASCs), as a fascinating cell source, have received much attention in tissue repair and regeneration. In this study we evaluated the potential of acellular dermal matrix (ADM) scaffold serving as a carrier for the delivery of ASCs and investigated its therapeutic effects on wound healing. First, ASCs were isolated and characterized for multidifferentiation potential. ASCs–ADM grafts were then prepared, and ADM scaffold was shown to support the in vitro growth and proliferation of ASCs. Next, we analysed paracrine factors in conditioned medium and found that ASCs–ADM grafts secreted various cytokines, including VEGF, HGF, TGFβ and bFGF. Moreover, ASCs–ADM conditioned medium notably stimulated the migration and proliferation of fibroblasts. In vivo, we established an excisional wound model in diabetic rats which received phosphate-buffered saline (PBS), ADM or ASCs–ADM grafts, respectively. Our results demonstrated that implantation of ASCs–ADM significantly enhanced tissue regeneration and increased epithelialization, resulting in accelerated wound closure. Immunofluorescence analysis further indicated that capillary density was evidently increased in the ASCs–ADM group compared with the control or ADM group. In addition, western blot analysis showed that ASCs–ADM significantly increased the expression of angiogenic factors, which was consistent with in vitro data. Taken together, our results suggest that targeted delivery of ASCs via ADM scaffold accelerate diabetic wound healing through a paracrine mechanism, with enhanced granulation tissue formation and increased re-epithelialization and neovascularization. Copyright © 2012 John Wiley & Sons, Ltd.

Ancillary