Wound Healing

Exosomes have gained significant attention in recent years as a cell-secreted product, with their potential applications becoming a major focus in the field of biomedicine. In the context of wound healing, exosomes are emerging as a promising new therapeutic approach.

Wound healing is a complex process involving the coordinated action of multiple cells and biological molecules, and can be primarily divided into four stages:

1. Hemostasis Phase: This phase i promotes platelet aggregation and blood clotting at the wound site to prevent further blood loss and protect the wound.

2. Inflammation Phase: Platelets contain various cytokines and growth factors in their cytoplasmic α-granules, such as PDGF, TGF-β, EGF, and IGF, which can attract neutrophils, macrophages, endothelial cells, and fibroblasts to the wound site. Neutrophils function to remove debris from the wound site and prevent bacterial infections. Macrophages, in addition to phagocytosing consumed neutrophils, bacteria, and damaged tissue, also induce and activate cells that play crucial roles in the subsequent proliferative phase, such as keratinocytes, fibroblasts, and endothelial cells, while also promoting angiogenesis.

3. Proliferation Phase: As inflammation subsides and the numbers of neutrophils and macrophages decrease, it signifies the start of the proliferation phase. During this period, the hypoxic environment near the wound can stimulate surrounding cells to release a range of angiogenesis-related factors, such as FGF, VEGF, PDGF, angiogenin, TGF-α, and TGF-β. These factors promote the proliferation of endothelial cells to form new microvessels, enabling the newly formed vessels to supply oxygen and nutrients necessary for the proliferation of fibroblasts. Fibroblasts also synthesize a series of provisional extracellular matrix components, including collagen, to enhance the strength of the healing wound. At this stage, the wound is occupied by proliferating fibroblasts, endothelial cells, new blood vessels, inflammation-related cells, and collagen, forming granulation tissue.

4. Maturation and Remodeling Phase: At this stage, the wound has completely healed, with fibroblasts covering the entire wound and forming new epidermis. Type III collagen, which is prevalent during the proliferation phase, is replaced by type I collagen. The disorganized collagen fibers are realigned, cross-linked, and arranged along tension lines, increasing in strength over time. Scar tissue loses its red appearance as new blood vessels are removed through apoptosis due to reduced activity in the wound area.

In the treatment strategy for wound healing, human mesenchymal stem cells (hMSCs) have gathered attention for their therapeutic efficacy in promoting wound repair. Due to their multi-lineage differentiation potential and immunomodulatory effects mediated by the paracrine secretion of various cytokines, hMSCs can accelerate the repair process described above, showing promising therapeutic effects on wound healing. Moreover, hMSCs can be isolated from various tissues in the human body, including adipose tissue, muscle, umbilical cord, and bone marrow. However, challenges such as high culture costs, difficult preservation, and potential carcinogenic risks hinder the widespread use of stem cell therapy.

Exosomes, as mediators of intercellular communication, can directly deliver messages and bioactive components to damaged tissues, effectively promoting wound repair and regeneration. Numerous studies have demonstrated that exosomes derived from hMSCs can release bioactive molecules including growth factors, messenger RNA, and other factors that regulate cell proliferation, promote angiogenesis, reduce inflammation, and accelerate the wound healing process. Studies have shown the potential of exosomes in promoting healing for various types of wounds, including chronic wounds, burns, and surgical wounds. Exosome therapy not only accelerates healing but also improves wound quality, reduces scar formation and infection risk, and enhances patients' quality of life.

Although exosome therapy is still in its early stages of clinical application, its potential has gathered widespread attention and expectations. With further understanding of the biological functions of exosome and continuous technological advancements, it is believed that exosomes will become a highly promising approach for wound healing, offering more effective and quicker treatment options for a wide range of patients.

Reference:

Huynh, P. D., Tran, Q. X., Nguyen, V. Q., & Vu, N. B. (2022). Mesenchymal stem cell therapy for wound healing: an update to 2022. Biomedical Research and Therapy, 9(12), 5437-5449.

Narauskaitė, D., Vydmantaitė, G., Rusteikaitė, J., Sampath, R., Rudaitytė, A., Stašytė, G., Aparicio Calvente, MI., & Jekabsone, A. (2021). Extracellular vesicles in skin wound healing. Pharmaceuticals, 14(8), 811.

Velnar, T., Bailey, T., & Smrkolj, V. (2009). The wound healing process: an overview of the cellular and molecular mechanisms. Journal of international medical research, 37(5), 1528-1542.

Zhao, H., Li, Z., Wang, Y., Zhou, K., Li, H., Bi, S., ... & Zhang, Z. (2023). Bioengineered MSC-derived exosomes in skin wound repair and regeneration. Frontiers in Cell and Developmental Biology, 11, 1029671.

Zhou, C., Zhang, B., Yang, Y., Jiang, Q., Li, T., Gong, J., ... & Zhang, Q. (2023). Stem cell-derived exosomes: emerging therapeutic opportunities for wound healing. Stem Cell Research & Therapy, 14(1), 107.