Relationship Between Keloid Pathogenesis and Endothelial Progenitor Cells: A Review Study

Context: Keloid scars are disfiguring lesions (ie, reddish-brown bulges on the skin surface) formed after a minor injury or surgical invasion. They lead to severe itching or pain, thereby causing physical and psychological distress in patients. Evidence Acquisition: Scholarly databases, including Web of Science, PubMed, and Google Scholar, were searched for relevant articles using keywords such as “keloids,” “endothelial progenitor cells” (EPCs), and “CD34-positive cells.” Results: Keloid scars are classified as an intractable disease; their cause is unknown, and there is no specific therapy. Their pathogenic effects on inflammation around wounds and fibroblasts have been extensively studied. However, details regarding their onset mechanism and definitive factors that contribute to their formation have not yet been elucidated. Adult stem cell therapy, especially regenerative therapy aimed at recovering tissue structure and function, has been extensively studied globally. In our recently published study, we identified an association between keloid scar development and EPCs. However, there is still no systematic review in this regard. Conclusions: This paper provides information on preventing keloids and further understanding the cause of this disease by reviewing previous studies on the association between keloids and EPCs.

Evaluating serum level of thymidylate synthase in post burn keloid patients before and after intralesional injection of 5-fluorouracil

Background Keloids are fibrous lesions formed at the site of trauma due to types I and III collagen irregular production. The presence of thymidylate synthase (TS) is a must for DNA synthesis and repairs causing cell death. 5-fluorouracil (5-FU) is a fluorinated pyrimidine analogue acting as an anti-metabolic agent that inhibits thymidylate synthase and interferes with ribo-nucleic acid (RNA) synthesis. Objectives we aimed to evaluate the level of thymidylate synthase in post burn keloid patients before and after intralesional injection of 5-fluorouracil. Methods The study included 20 keloid patients and 20 healthy subjects as a control. Serum TS was estimated using commercially available enzyme-linked immunosorbent assay (ELISA) kits before and after treatment with 5-fluorouracil. Results There was a statistically significant difference in TS levels before and after 5-FU treatment (p < 0.05). Also, results have shown that 5-FU injection has good satisfactory results in treatment of keloid causing reduction in scar volume and symptoms improvement (90% of the patients improved). On the other hand, there was no statistically significant difference in TS levels and the outcomes of the treatment. Conclusion Our findings suggest that intralesional 5-FU injection in keloid has very satisfactory results. However, thymidylate synthase enzyme has a minimal role in evaluating the treatment of keloid, so further studies are required to elaborate the relation between this enzyme and keloid scars.

Umbilical trocar port site keloid management using a transposition flap after laparoscopic surgery

Background Keloids can occur anywhere in the human body. They are difficult to remove and can cause distress in patients. Although many options are available to treat keloids, no single method is considered the optimal treatment of choice. The authors encountered cases where an umbilical keloid developed at the trocar site after laparoscopic surgery and managed the keloid using a transposition flap.Methods A total of 10 umbilical keloid patients treated from 2013 to 2020 were included in this study. All patients developed a keloid due to the placement of a laparoscopic trocar incision port, and their major complaints varied from an asymptomatic nodule to pruritus or pain. All excisions were performed under local anesthesia, and transposition flaps were planned afterward. The surrounding tissue was rearranged so that the shape of the umbilicus was deformed to the minimum extent possible. The keloid scars were examined both preoperatively and 6 months postoperatively using the Patient and Observer Scar Assessment Scale (POSAS).Results All surgical wounds healed well without complications. The average time interval from laparoscopic surgery to keloid scar revision was 4.3 years. The mean postoperative follow-up period was 10.9 months, and no patient underwent reoperation. Four patients were treated with triamcinolone after surgery due to mild hypertrophy or pruritus. The POSAS observer scale showed significantly decreasing scores over time in all patients (P=0.002).Conclusions Cosmetically unfavorable keloids that form in the umbilicus following laparoscopic surgery can be improved with a simple procedure using excision and transposition flaps.

Therapeutic candidates for keloid scars identified by qualitative review of scratch assay research for wound healing

The scratch assay is an in vitro technique used to analyze cell migration, proliferation, and cell-to-cell interaction. In the assay, cells are grown to confluence and then ‘scratched’ with a sterile instrument. For the cells in the leading edge, the resulting polarity induces migration and proliferation in attempt to ‘heal’ the modeled wound. Keloid scars are known to have an accelerated wound closure phenotype in the scratch assay, representing an overactivation of wound healing. We performed a qualitative review of the recent literature searching for inhibitors of scratch assay activity that were already available in topical formulations under the hypothesis that such compounds may offer therapeutic potential in keloid treatment. Although several shortcomings in the scratch assay literature were identified, caffeine and allicin successfully inhibited the scratch assay closure and inflammatory abnormalities in the commercially available keloid fibroblast cell line. Caffeine and allicin also impacted ATP production in keloid cells, most notably with inhibition of non-mitochondrial oxygen consumption. The traditional Chinese medicine, shikonin, was also successful in inhibiting scratch closure but displayed less dramatic impacts on metabolism. Together, our results partially summarize the strengths and limitations of current scratch assay literature and suggest clinical assessment of the therapeutic potential for these identified compounds against keloid scars may be warranted.