The Role of UCMSC Derived Secretome in Collagen Remodeling During Skin Photoaging Molecular Mechanisms and Therapeutic Potential

Abstract

Introduction: Skin photoaging is characterized by progressive disruption of the dermal extracellular matrix, particularly an imbalance between collagen synthesis and degradation. Umbilical cord mesenchymal stem cell-derived secretome has emerged as a promising cell-free regenerative approach because it contains soluble factors and extracellular vesicles capable of influencing skin repair and collagen homeostasis.Methods: A structured literature search was conducted in PubMed, Scopus, and ScienceDirect for studies published from January 2016 to June 2026. Studies evaluating conditioned medium, whole secretome, extracellular vesicles, or exosomes derived from umbilical cord or Wharton’s jelly mesenchymal stem cells in skin aging, photoaging, ultraviolet-induced skin damage, or collagen remodeling were included. The study-selection process followed the PRISMA 2020 framework. Of 166 identified records, 14 studies were included in the narrative synthesis.Results: Most evidence was derived from in vitro, ex vivo, and animal studies, while human evidence was limited to small, short-term investigations. UCMSC-derived products were associated with increased collagen expression, procollagen production, collagen deposition, and improved dermal organization. They also reduced collagen-degrading matrix metalloproteinases and supported fibroblast survival. The proposed mechanisms involved antioxidant, anti-inflammatory, antisenescence, and extracellular-matrix-regulatory pathways. Comparative findings suggested that UCMSC-derived secretome may have particular antioxidant and antisenescence advantages, although it was not consistently superior to secretomes from other MSC sourcesConclusion: UCMSC-derived secretome shows potential for supporting collagen remodeling in photoaged skin. However, methodological heterogeneity, inconsistent product characterization, and limited controlled clinical evidence prevent definitive conclusions. Standardized manufacturing and well-designed clinical trials are required to establish its efficacy, safety, and clinical applicability