Background: The efficacy of adipose-derived mesenchymal stem cells (ADMSCs) secretome for skin aging has been established, yet no studies hitherto directly investigated the best administration method for such purpose. Purpose: We aimed to compare microneedling (MN) versus fractional CO₂ laser (FL) as methods of delivery for ADMSCs secretome in the treatment of aging skin. Patients and Methods: A single-blind, randomized split-face clinical trial was conducted on 30 Indonesian women (aged 35– 59 years old) with signs of facial cutaneous senescence. Their initial aging status was assessed by dermoscopy photoaging scale (DPAS) and Janus-III measurement system. In the second and fourth weeks, all participants were treated with both MN and FL, followed by the application of a four-fold concentrated ADMSC secretome. The assignment of which side of the face received MN or FL was done by computer-based randomization. Skin parameters were reevaluated on the fourth and sixth weeks, along with patient satisfaction, level of comfort, preference for administration techniques, and also adverse events experienced during the study. Appropriate statistical analyses were subsequently performed at a significance level of 0.05. Results: Significant improvements in total DPAS and wrinkles were found in the MN and FL groups at the end of the trial. In contrast, no statistical differences in all parameters were observed between groups in the fourth and sixth weeks. FL scored higher than MN for satisfaction and preference, but lower in terms of comfort. Pain, burning sensation, and itch were the side effects experienced by subjects upon treatment. Two patients had prolonged reddish skin succeeding FL treatment, which relieved with moisturizer application. Conclusion: Both MN and FL yielded comparable results for improving several skin aging features. However, subjective preference for ADMSCs secretome administration method may differ when considering satisfaction, comfort, and possible adverse events.

Response to Letter in regards to A Comparative Study on Adipose-Derived Mesenchymal Stem Cells Secretome Delivery Using Microneedling and Fractional CO2 Laser for Facial Skin Rejuvenation [Letter]

Background/Purpose: COVID-19 pandemic has compromised healthcare services in dermatology and venereology. Given such circumstances, studies investigating the consultation pattern of related fields in hospitals were relatively scarce. The present study aimed to delineate such matter from tertiary hospital viewpoint. Methods: Details concerning referred patients from the emergency room, inpatient wards, intensive care unit, and nursery to the Department of Dermatology and Venereology, Dr. Cipto Mangunkusumo Hospital were retrospectively collected from electronic health records. Cases admitted in the 17 months span before and during COVID-19 global outbreak were included. The obtained data were presented descriptively, and Chi-squared test was performed upon attributes of interest at a significance level of 0.05. Results: A slight increase of total consultation was found in the COVID-19 era with an initial reduction at the beginning (April–May 2020). One-time consultation was the most inquired to our department in both periods of which dermatitis was the most prevalent case and Gram staining was the most common examination. Topical antibiotics and emollient were the most prescribed medications before and during the outbreak, respectively. The conformity of initial-final decision, appropriateness of initial-final diagnosis, and consult response time were significantly different (p < 0.05) between the two groups. Conclusion: There were changes of the number of consultation requests in the pandemic era with statistically significant change of decision conformity, diagnoses, appropriateness, and consult response time. Although some changes appeared, the most prevalent diagnoses remained.

Skin hypopigmentation and atrophy are the most commonly reported local adverse effects following corticosteroid application. While these changes are typically reversible, the recovery may be delayed or incomplete in older adults due to diminished physiological reserves and age‐related reductions in melanocyte function and dermal regenerative capacity. Adipose‐derived mesenchymal stem cells (ADMSCs) secretome may offer substantial benefits in reversing the alterations. In this report, we present the clinical evaluation of an elderly patient with steroid‐induced cutaneous manifestations receiving ADMSCs secretome administered with intradermal injection and microneedling. Given that corticosteroid‐induced atrophy and hypopigmentation may improve spontaneously, this case does not establish treatment efficacy; rather, it describes a clinical observation. The potential mechanisms by which ADMSCs secretome may facilitate improvement are also discussed.

Skin aging is characterized by epidermal atrophy, reduced keratinocyte proliferation, and the accumulation of senescent cells that sustain a chronic, low-grade inflammatory secretome known as the senescence-associated secretory phenotype (SASP). We previously showed that Y-box binding protein 1 (YBX1) limits keratinocyte senescence in human epidermis by acting as a translational repressor of SASP chemokines, including CXCL1 and IL8. How this brake is regulated during skin aging, however, remains undefined. Here we demonstrate that, although total YBX1 protein is reduced in keratinocytes from aged human epidermis, the fraction of phosphorylated YBX1 (pYBX1) is increased relative to young donors, resulting in an elevated pYBX1/total YBX1 ratio that correlates with chronological age. Because pYBX1 is predominantly nuclear, whereas unphosphorylated YBX1 is cytoplasmic, this shift is predicted to deplete the cytoplasmic pool available for translational repression of CXCL1 and IL8. Consistent with this model, treatment of immortalized (Ker-CT) and primary human keratinocytes (HK) with the PI3K inhibitors PI-103 and GDC-0941 suppressed YBX1 phosphorylation without altering total YBX1 abundance, thus retaining YBX1 in the cytoplasm. This allows cytoplasmic YBX1 to re-engage and repress the translation of CXCL1 and IL8 mRNAs, lower chemokine secretion, and reduce the fraction of senescent keratinocytes. Moreover, conditioned medium from PI-103- or GDC-0941-treated cells sufficiently decreased senescence in recipient cells, consistent with a paracrine, secretome-mediated effect. Together, these findings support an association between YBX1 phosphorylation and SASP chemokine output in aging human keratinocytes and nominate YBX1-directed modulation as a candidate strategy for selectively attenuating senescence-associated secretory phenotypes in intrinsic skin aging.