Mesenchymal Stem Cell-Derived Exosome Treatment for Acne Scars: An Alternative Therapy

Table 2. Patient and Observer Scar Assessment Scale (POSAS).

Treatment

The goal of acne scar treatment is to reduce the appearance of scars and smooth the skin. Below is a summary of treatment options:

Topical treatments

• Topical Retinoids: Can improve skin texture and reduce the appearance of superficial scars.
• Silicone Gel or Patch: Used to improve the appearance of hypertrophic scars and keloids.

Procedural treatments

• Microneedling: Uses fine needles to create small punctures in the skin, stimulating collagen and elastin production, thus promoting mechanical abrasion over damaged areas. The penetration is superficial, removing the outer layer of the dermis and accelerating the natural exfoliation process.
• Laser Therapy (Fractional CO2 Laser, Erbium Laser): Removes superficial skin layers and stimulates collagen production, improving texture and reducing scar depth. The choice of laser type should consider the nature of the scar, patient tolerance, and expectations. Patients with boxcar scars are the best candidates [10].
• Sub Cision: A procedure where a Nokor needle is inserted under the skin adjacent to the scar with the bevel up on the deep dermis. Fan-like movements are performed to break the fibrous bands causing the rolling scars. Improvement is observed 6 months post- treatment [11].
• Dermal Fillers (Hyaluronic Acid): Used to elevate depressed scars, providing a more even skin surface. Effective for boxcar scars but not for ice-pick scars [12].
• High-Power Chemical Peels: Apply strong acids to remove superficial skin layers and promote regeneration. More effective on macular scars compared to deeper ice-pick and rolling scars, which require periodic sequential peels for better results [13].

Biological and regenerative treatments

• Platelet-Rich Plasma (PRP): A mixture of high-concentration platelets with growth factors, obtained by one-phase centrifugation of blood tissue. It contains large amounts of proteins like platelet-derived growth factor, beta fraction growth factor, epithelial growth factor, and adhesion molecules. Injected into the skin to promote cellular regeneration and collagen production [14].
• Mesenchymal Stem Cell-Derived Exosomes: Contain growth factors and bioactive molecules that promote skin repair and regeneration, significantly improving acne scars.
• Treating acne scars involves a multifaceted approach, and the choice of treatment should be tailored to the scar type, skin type, and specific patient preferences. A combination of multiple treatments often yields the best results.

Exosomes

Exosomes are    extracellular      nanovesicles, typically between 30-200 nanometers in diameter, released by cells as a means of communication, tissue repair, and immunomodulation (Figure 2.A). These nanovesicles contain a significant amount of lipids, proteins, and genetic material such as mRNA and miRNA. Additionally, exosomes possess anti-inflammatory and immunomodulatory properties, making them ideal for addressing facial laxity (Figure 2.B).

Recently, exosomes have gained prominence in the cosmetic world. Studies have shown that exosomes are beneficial for skincare due to their high content of proteins, lipids, and other molecules that can promote healing, hydration, and skin protection. These molecules have the potential to stimulate collagen production, reduce inflammation, and protect the skin against the negative effects of the environment. Exosomes also have the ability to reduce reactive oxygen species (ROS) and TNF-α while increasing TGF- β, leading to an increase in MMP-1 and type I procollagen [15].

Moreover, cytokines, nucleic acids, proteins, and other bioactive substances present in exosomes can help protect the skin from harmful environmental factors and reduce dark spots and discoloration. Exosome therapy can be applied topically or injected directly into scar tissue. Injections are often used to treat deeper scars due to their effective penetration into the dermis where the scar tissue resides. Topical applications may be more suitable for treating superficial scars, as they allow for a more uniform distribution of therapeutic agents. Clinical studies have confirmed that exosome therapy is safe and effective for scar removal. It has the potential to reduce the appearance of skin marks, increase skin hydration and elasticity, and decrease inflammation. Additionally, it can help strengthen the skin's natural defenses against infections.

Exosomes derived from umbilical cord mesenchymal stem cells (UCMSC) have an increased concentration of certain microRNAs, such as miR-21, miR-23a, miR-125b, and miR- 145 [16]. Furthermore, exosomes rich in miR-21-3p were found to promote epithelial regeneration, reduce scar size, and stimulate the formation of new blood vessels by inhibiting PTEN and SPRY1 [17].

Accordingly, it can be inferred that exosomes derived from mesenchymal stem cells (MSCs), including ADSC-exos, could regulate fibroblast function and collagen production to promote scar- free healing. Therefore, exosomes derived from umbilical cord mesenchymal stem cells could be a viable therapeutic option for promoting wound healing, preventing scar formation and reducing scar appearance.

Figure 2 (A): Schematic Representation of Exosome Biogenesis and Secretion

 Figure 2 (B): Molecular Components of Exosomes (Tenchov 2022).

Case Report

A 33-year-old female patient with no relevant medical history experienced recurrent nodules and papules of acne vulgaris on her face during adolescence. Initial treatment included facial cleanings and laser sessions without the need for antibiotics. To maintain the treatment, weekly facial cleanings were conducted along with the use of topical medications, which temporarily controlled the condition.

Subsequently, at the age of 24, the patient developed nodular cystic acne, a more severe form of the condition, which persisted for two to three years. During this period, she was administered isotretinoin at a dose of 20 mg per day for eight months on three different occasions. The patient noted that during this period, she did not use facial moisturizers or UV sunblock and engaged in self-manipulation of the acne. Nevertheless, she continued with biweekly facial cleanings and the use of antiseborrheic soap.

At the age of 30, the patient observed an improvement in her acne condition. However, she began to develop residual ice pick scars, boxcar scars, rolling scars, and hyperpigmentation (Figure 3). To address these scars, she underwent several aesthetic procedures. Initially, three sessions of glycolic acid chemical peels were performed, significantly improving skin hyperpigmentation. Subsequently, four sessions of CO2 laser treatment were applied, resulting in a notable improvement in ice pick scars. To complement these treatments, the patient incorporated subcision treatments and topical treatments, which included the use of sunscreen, morning vitamin C, moisturizer both in the morning and at night, topical and oral retinol (soluble vitamin A), and three applications of collagenase.

Figure 3: Patient Admission with Ice Pick, Boxcar, and Rolling Scars. (A) Right Hemisphere (B) Right Hemisphere (C) Left Hemisphere

Additionally, advanced therapies such as the use of Skin Booster and PRP were implemented, with continuous deep cleanings once a month. The patient also began supplementing with megadoses of vitamin C, observing a significant disappearance of acne along with a drastic change in diet. Furthermore, hyaluronic acid filler was applied directly to the scars in three sessions, with a frequency of once every four months.

The patient presented to the clinic with boxcar scars, rolling scars, ice pick scars, and hyperpigmentation, scoring 180 points on the Acne Scar Clinical Evaluation Scale (ECCA). After the examination, pre-treatment photos were taken for case follow-up. The patient's treatment plan included two sessions of subcision and Flow exosome treatment, followed by two sessions of PRP applied with microneedling, with a 45-60 day interval between each treatment.

Figure 4: Control photos at the beginning of the treatment showing ice pick scars, rolling scars, boxcar scars, and hyperpigmentation. Scoring 180 on the ECCA scale (A) Right hemisphere (B) Left hemisphere.

The treatment was applied using subcision with a Nokor needle and exosome infiltration with a 25g cannula in a radiated manner in the deep dermal plane to stimulate extracellular matrix production, reduce fibrosis, and decrease inflammation. Flow exosomes from the Cellgenic brand were used, containing 30 billion exosomes derived from umbilical cord mesenchymal stem cells from Wharton's jelly. These exosomes contain trace elements, amino acids, interleukins, vitamins, growth factors, and proteins (Table 3-5).

Results

The patient showed a remarkable evolution in the condition of her skin, from common acne to nodular cystic acne and scarring acne of different types. Multiple management strategies, including dermatological procedures, changes in skincare regimen, and diet, allowed the patient's dermis to appear more uniform. Therapeutic novelties offered, such as exosomes and PRP, which efficiently complement traditional and aesthetic therapies, proved to be highly effective in substantially improving skin tissue and reducing residual marks in the discussed patient. The ECCA score decreased from 180 to 90 points over the course of the sessions, demonstrating a significant improvement in skin appearance.

Conclusion

Subcision with Flow exosomes proved highly effective for severe acne scars. Precise infiltration of exosomes into affected areas led to significant regeneration of scar tissue by promoting collagen formation, improving skin texture, and color. Additionally, angiogenesis promoted by exosomes enhanced skin oxygen supply while also promoting greater nutrition, favoring skin tissue repair and a healthy facial appearance. Furthermore, PRP sessions with microneedling were a beneficial addition to the treatment, contributing to regenerative action and accelerating the healing process. As PRP has regenerative effects, the combination of PRP and exosomes created a favorable environment for skin restoration. The comprehensive treatment of acne and its scars in this patient highlights the need for advanced and individualized approaches. This combination of subcision, exosomes, and PRP was highly effective for the treatment of severe acne scars and resulted in notable improvements in scar regeneration and appearance. In this case, the potential aesthetic benefits of exosomes in dermatology were demonstrated, highlighting their potential as an effective tool for skin regeneration and the treatment of difficult-to-treat scars.

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