Advanced lyophilized mesenchymal stem cell-conditioned medium formulation improves therapeutic efficacy in skin wound repair

Abstract The secretome of human umbilical cord mesenchymal stem cells (hUC-MSCs) represents a promising cell-free therapeutic approach for wound healing because of its rich composition of bioactive factors that promote tissue repair. However, the clinical translation of secretome-based therapies is hindered by the instability of its bioactive components during storage. To address this challenge, we developed a lyophilization strategy using cryoprotectants to produce a stable, powdered form of hUC-MSC-conditioned medium (CM). Our results demonstrated that the lyophilized CM (Lyo-CM), particularly when formulated with specific cryoprotectants, maintained excellent bioactivity of CM while showing superior reproducibility and stability. Furthermore, both in vitro and in vivo experiments revealed that Lyo-CM significantly enhanced wound closure during inflammation and proliferation phases, including inflammation resolution, cell proliferation, angiogenesis, and extracellular matrix remodeling. Our study provides a valuable approach to establishing a clinically viable, shelf-stable formulation of hUC-MSC secretome to advance the field of cell-free regenerative therapy.