# Efficacy and Tolerability of a Microneedling Device Plus Exosomes for Treating Melasma
## 4 Discussion
Stem cell-derived exosomes (SC-Exos) are lipid-bilayer nanovesicles with 30-200 nm molecular diameter. They are produced and secreted from the cells and act as extracellular messengers. SC-Exos share attributes to stem cells (SCs), in addition to the advantages of enhanced stability and low immunogenicity. With antiaging, anti-inflammatory, and antioxidation properties, SC-Exos contribute to skin whitening and promote skin regeneration. In particular, rose stem cell exosomes (RSCEs) promote growth of skin fibroblasts and collagen production, reduced melanin production in melanocytes, and inhibition of inflammation [35]. However, exosomes encounter difficulty penetrating the skin barrier. Recently, it has been demonstrated that microneedling is an effective and safe penetration-promoting method in the treatment of melasma, enhancing the percutaneous penetration of SC-Exos [33]. The presented study underscores the potential efficacy of the combination of _Rosa damascena_ stem cell exosomes and microneedling in addressing melasma. It is noteworthy to emphasize that our work benefits from a highly diversified patient sample, representing a strong point of our research. The analysis encompassed both male and female participants, individuals spanning various age groups, and those with different Fitzpatrick skin types. Ninety percent of subjects demonstrated a significant improvement in mMASI scores, while only ten percent showed no change. GAIS assessment further supports overall improvement, with just 10% categorized as \"not changed\". Tolerability was favorable, marked by mild and transient side effects. It is essential to highlight the variability in responses among subjects, particularly the distinctions between those experiencing better outcomes (transition to mild mMASI) and those with less improvement (transition to moderate mMASI). Notably, half of the subjects not improving in mMASI had a mild form at baseline. This could be attributed to their condition being closer to the desired outcome with fewer pigmentary changes. The totality of subjects with moderate melasma at baseline responded well to treatment, transitioning to mild mMASI. This indicates that this kind of patient may be more receptive to the combined therapy, possibly due to less entrenchedmelanin deposition or more responsive skin physiology. Fifty percent of the subjects exhibited severe melasma, and all demonstrated a positive response, indicating the efficacy of the combined therapy even in challenging cases. This raises optimism for individuals traditionally deemed to have less favorable prognosis. However, within the severe melasma group, diverse responses were observed. While 40% showed improvement to mild mMASI, 60% transitioned to moderate mMASI, possibly indicating a subgroup less responsive to the intervention, influenced by intrinsic factors or a longer history of melasma. Notably, the absence of severe adverse reactions and post-inflammatory hyperpigmentation, with increased attention to individuals with darker skin types (Fitzpatrick III), along with the perception of the treatment as well-tolerated, indicates a positive safety profile. Finally, the observation that the only subjects not experiencing improvement in GAIS were those who did not undergo the maximum five sessions raises questions about the correlation between the number of sessions and treatment efficacy. This suggests that completing the entire treatment course is crucial for achieving optimal outcomes and discontinuing prematurely might limit the intervention's effectiveness.