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Fibroblast-derived Extracellular Vesicles Effectively Induce Wound Healing

Review of "Extracellular vesicles derived from fibroblasts promote wound healing by optimizing fibroblast and endothelial cellular functions" from STEM CELLS by Stuart P. Atkinson

While mesenchymal stem cell-derived extracellular vesicles can contribute to enhanced wound healing [1, 2], their isolation suffers from certain drawbacks that represent barriers to their widespread use [3-5]. This vexing problem led researchers from the laboratories of Ho Yun Chung and Byeong‐Cheol Ahn (Kyungpook National University, Daegu, South Korea) to identify another cell source that produced large numbers of extracellular vesicles with pro‐wound healing abilities. In their recent STEM CELLS article [6], Oh et al. now report that extracellular vesicles derived from mouse skin fibroblasts [7] represent an exciting alternative to those derived from mesenchymal stem cells, as shown by their studies employing an in vivo mouse model of full‐thickness wound healing.

The authors isolated and purified extracellular vesicles from mouse connective tissue fibroblasts (L929 cell line) and then demonstrated how they possessed the ability to induce fibroblast proliferation and migration and increase the expression of genes associated with scarless wound healing (i.e., MMP1, MMP3, and COL3A1) following uptake, suggesting pro‐wound healing capabilities. In this respect, fibroblast-derived extracellular vesicles also induced migration and enhanced tube forming ability following uptake by endothelial cells.

Given these positive indications, the authors moved in vivo, where they evaluated a combination of fibroblast-derived extracellular vesicles with a commercially available fibrin glue as a novel approach to improve wound healing in a mouse model of full‐thickness wound healing. Encouragingly, they discovered that extracellular vesicles accelerated full‐thickness wound healing by supporting normal skin density and composition, enhancing collagen formation and maturation, increasing blood vessel growth, and possibly initiating hair growth.

Overall, these findings provide evidence of fibroblast‐derived extracellular vesicle administration as a novel and effective wound healing approach that avoids the involvement of mesenchymal stem cells. The authors' subsequent research hopes to explore the extracellular vesicle cargoes responsible for wound healing (e.g., proteins and microRNAs) and establish the mechanism by which extracellular vesicles regulate proliferation, migration, and tube formation.

For more on the wound healing power of fibroblasts-derived extracellular vesicles, stay tuned to the Stem Cells Portal!


  1. Hu P, Yang Q, Wang Q, et al., Mesenchymal stromal cells-exosomes: a promising cell-free therapeutic tool for wound healing and cutaneous regeneration. Burns & Trauma 2019;7.
  2. Casado-Díaz A, Quesada-Gómez JM, and Dorado G, Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing. Frontiers in Bioengineering and Biotechnology 2020;8:146.
  3. Ramakrishnan A, Torok-Storb B, and Pillai MM, Primary Marrow-Derived Stromal Cells: Isolation and Manipulation, in Stem Cell Niche: Methods and Protocols, K. Turksen, Editor. 2013, Humana Press: Totowa, NJ. p. 75-101.
  4. Horn P, Bork S, and Wagner W, Standardized Isolation of Human Mesenchymal Stromal Cells with Red Blood Cell Lysis, in Mesenchymal Stem Cell Assays and Applications, M. Vemuri, L.G. Chase, and M.S. Rao, Editors. 2011, Humana Press: Totowa, NJ. p. 23-35.
  5. Maumus M, Rozier P, Boulestreau J, et al., Mesenchymal Stem Cell-Derived Extracellular Vesicles: Opportunities and Challenges for Clinical Translation. Frontiers in Bioengineering and Biotechnology 2020;8:997.
  6. Oh EJ, Gangadaran P, Rajendran RL, et al., Extracellular vesicles derived from fibroblasts promote wound healing by optimizing fibroblast and endothelial cellular functions. STEM CELLS 2021;39:266-279.
  7. Li B and Wang JHC, Fibroblasts and myofibroblasts in wound healing: Force generation and measurement. Journal of Tissue Viability 2011;20:108-120.