New Fibroblast Type Identified as Key Player in Overgrown Scar Formation and Recurrence

Recent research has uncovered a specific subtype of fibroblast that may play a crucial role in the development and recurrence of keloids—raised, overgrown scars that often extend beyond the original wound area. These scars can cause significant physical discomfort, including pain, itching, and limited mobility, making their management particularly challenging. Current treatments such as surgical removal, steroid injections, and radiation therapy often face high recurrence rates, sometimes reaching 30%, underscoring the need for better understanding and targeted therapies.

Keloids have long puzzled scientists because they grow uncontrollably, unlike hypertrophic scars which typically remain contained. While excess collagen production by fibroblasts is known to be involved, the triggers for this abnormal tissue growth and the cellular mechanisms behind it remain unclear. A recent study published in the Journal of Pathology on September 1, 2025, by a research team at Chiba University in Japan, offers new insights by examining the molecular and cellular differences in keloid tissue.

Leading researcher Professor Yuzuru Ikehara explained that by comparing fibrotic tissues from different conditions—specifically keloids and lymphedema, which involves fibrosis without significant mechanical tension—the team aimed to identify unique features of keloid fibroblasts. Advanced techniques like gene expression profiling and single-cell RNA sequencing revealed that keloids exhibit heightened expression of PIEZO2, a mechanosensitive ion channel that functions as a cellular force sensor.

Interestingly, fibroblasts expressing high levels of PIEZO2, termed FB PZ2+, were found to be particularly active in producing collagen and other extracellular matrix components. These cells tend to cluster around blood and lymphatic vessels within the scar tissue, especially in areas of active growth, suggesting their pivotal role in driving scar expansion and recurrence.

The study emphasizes that connective tissue—is composed not only of fibroblasts but also immune cells, blood vessels, and nerves—all working together to maintain tissue homeostasis. By isolating and understanding the role of PIEZO2-expressing fibroblasts, researchers hope to develop targeted therapies. For instance, PIEZO2 inhibitors could potentially reduce the mechanical stimuli that trigger abnormal scar growth, alleviating symptoms such as pain and itching.

This discovery marks an important step toward precision medicine for keloid treatment. It hints at the possibility of novel diagnostic tools that identify risk of recurrence by measuring PIEZO2 levels and opens avenues for therapies that directly modulate mechanosensitive pathways. Future approaches could modify scar tissue formation at the cellular level, ultimately improving patient outcomes and quality of life.

For more detailed information, see the full study: Shinsuke Akita et al, "Increased expression of the PIEZO2 mechanoreceptor in fibroblasts and endothelial cells within the lymphatic and vascular vessels of keloids," The Journal of Pathology, 2025. Source: https://medicalxpress.com/news/2025-10-fibroblast-contribute-formation-recurrence-overgrown.html