The cellular players that enable wound healing

A coordinated effort between the stroma, the immune system, and the skin microbiome restores damaged skin.

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The cellular players that enable wound healing
By luisa torres phd, designed by imran chowdhury





From Cut to Cure 

Healing skin injuries such as cuts, burns, or puncture wounds requires diverse cell types and signaling molecules, including mesenchymal stem cells (MSCs), immune cells, and commensal skin bacteria. Interactions between these key players result in effective tissue repair and help restore the skin’s integrity and functionality.

Cleaning Up 

Injured cells release signaling molecules such as alarmins that activate MSCs to produce chemokines, which attract macrophages and neutrophils to the injury site. Macrophages and neutrophils clear debris and dead cells, causing swelling, heat, redness, and pain (1,2).

Closing the Wound 

Macrophages secrete growth factors, and commensal skin bacteria activate CD8+ T cells that prompt keratinocytes, specialized epithelial cells, to proliferate. Keratinocytes migrate from the wound edges to rapidly cover the wound surface (3,4).

Letting Nutrients In 

MSCs, macrophages, and neutrophils produce vascular endothelial growth factor (VEGF), which helps form new blood vessels. These vessels deliver nutrients, oxygen, and anti-inflammatory immune cells that facilitate tissue regrowth (1,5).

Reducing Wound Size 

Macrophages release cytokines that help MSCs differentiate into myofibroblasts, which form a collagen-rich layer that provides a scaffold for tissue regeneration (5). They also help contract the wound and apply tension to the wound edges, reducing wound size.

Making a Scar 

Myofibroblasts produce new collagen fibers that form strong and flexible scar tissue (2). Macrophages prevent excessive scarring by engulfing surplus collagen.

Fully Healed 

As the scar matures, most blood vessels, myofibroblasts, and inflammatory cells disappear through apoptosis. The final scar primarily consists of collagen and other structural components (5).

References 

  1. Harrell, C.R., Djonov, V., & Volarevic, V. The cross-talk between mesenchymal stem cells and immune cells in tissue repair and regeneration. Int J Mol Sci  22, 2472 (2021). 
  2. Guillamat-Prats, R. The role of MSC in wound healing, scarring, and regeneration. Cells  10, 1729 (2021). 
  3. Pastar, I. et al. Epithelialization in wound healing: a comprehensive review. Advances in wound care  3, 445-464 (2014). 
  4. Johnson, T. R. et al. The cutaneous microbiome and wounds: new molecular targets to promote wound healing. International Journal of Molecular Sciences  19, 2699 (2018). 
  5. Gonzalez, A.C., Costa, T.F., Andrade, Z.A., & Medrado, A.R. Wound healing - a literature review. Anais brasileiros de dermatologia  91, 614–620 (2016).
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