Abstract
Introduction: Skin aging arises from intrinsic processes and extrinsic insults (e.g., ultraviolet exposure and oxidative stress). Mesenchymal stromal cell (MSC)-derived secretome offers a cell-free approach to skin regeneration. Wharton's jelly-derived MSCs (WJ-MSCs) may outperform adipose-derived (AD-MSCs) and bone marrow-derived MSCs (BM-MSCs). Methods: Secretomes from WJ-MSCs, AD-MSCs, and BM-MSCs were compared in vitro for human dermal fibroblast proliferation, scratch-wound closure, extracellular-matrix (ECM) remodeling, and type I procollagen secretion. Anti-inflammatory and antioxidant activities were assessed by IL-6, IL-1β, TNF-α, COX-2 and intracellular reactive oxygen species (ROS). Antibody arrays profiled secreted factors. An exploratory, single-arm human pilot (n = 21; 1-week) evaluated topical WJ-MSC secretome with paired analyses. Safety was monitored, and a separate occlusive patch test (n = 33) was conducted. Results: The WJ-MSC secretome increased fibroblast proliferation, ECM remodeling, and type I procollagen, and reduced cytokines and ROS, exceeding the effects of AD-MSC and BM-MSC secretomes. Profiling highlighted apolipoprotein A4 (ApoA4) and SERPINH1 as enriched, functionally active mediators; recombinant ApoA4 and SERPINH1 enhanced fibroblast activity, collagen-related readouts, and accelerated in vitro wound closure. In the pilot study, within-subject increases in instrument-derived hydration and elasticity were observed over one week (paired tests). No treatment-related adverse events were noted. Patch testing showed no irritation (ICDRG scores all 0; non-irritant classification). Conclusions: The WJ-MSC secretome demonstrated consistent in-vitro pro-regenerative, anti-inflammatory, and antioxidant activities, with ApoA4 and SERPINH1 as candidate mediators. Human findings are preliminary/exploratory and suggest potential short-term benefits that require confirmation in adequately powered, controlled trials.