Background and Objectives There have been contradictory reports on the pro-cancer or anti-cancer effects of mesenchymal stem cells. In this study, we investigated whether conditioned medium (CM) from hypoxic human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) (H-CM) showed enhanced anti-cancer effects compared with CM from normoxic hUC-MSCs (N-CM). Methods and Results Compared with N-CM, H-CM not only strongly reduced cell viability and increased apoptosis of human cervical cancer cells (HeLa cells), but also increased caspase-3/7 activity, decreased mitochondrial membrane potential (MMP), and induced cell cycle arrest. In contrast, cell viability, apoptosis, MMP, and cell cycle of human dermal fibroblast (hDFs) were not significantly changed by either CM whereas caspase-3/7 activity was decreased by H-CM. Protein antibody array showed that activin A, Beta IG-H3, TIMP-2, RET, and IGFBP-3 were upregulated in H-CM compared with N-CM. Intracellular proteins that were upregulated by H-CM in HeLa cells were represented by apoptosis and cell cycle arrest terms of biological processes of Gene Ontology (GO), and by cell cycle of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In hDFs, negative regulation of apoptosis in biological process of GO and PI3K-Akt signaling pathway of KEGG pathways were represented. Conclusions H-CM showed enhanced anti-cancer effects on HeLa cells but did not influence cell viability or apoptosis of hDFs and these different effects were supported by profiling of secretory proteins in both kinds of CM and intracellular signaling of HeLa cells and hDFs.

Light‐based therapy such as photobiomodulation (PBM) reportedly produces beneficial physiological effects in cells and tissues. However, most reports have focused on the immediate and instant effects of light. Considering the physiological effects of natural light exposure in living organisms, the latent reaction period after irradiation should be deliberated. In contrast to previous reports, we examined the latent reaction period after light exposure with optimized irradiating parameters and validated novel therapeutic molecular mechanisms for the first time. we demonstrated an organic light‐emitting diode (OLED)‐based PBM (OPBM) strategy that enhances the angiogenic efficacy of human adipose‐derived stem cells (hADSCs) via direct irradiation with red OLEDs of optimized wavelength, voltage, current, luminance, and duration, and investigated the underlying molecular mechanisms. Our results revealed that the angiogenic paracrine effect, viability, and adhesion of hADSCs were significantly intensified by our OPBM strategy. Following OPBM treatment, significant changes were observed in HIF‐1α expression, intracellular reactive oxygen species levels, activation of the receptor tyrosine kinase, and glycolytic pathways in hADSCs. In addition, transplantation of OLED‐irradiated hADSCs resulted in significantly enhanced limb salvage ratio in a mouse model of hindlimb ischemia. Our OPBM might serve as a new paradigm for stem cell culture systems to develop cell‐based therapies in the future.

Mesenchymal stem cells such as human adipose tissue‐derived stem cells (hADSCs) have been used as a representative therapeutic agent for tissue regeneration because of their high proliferation and paracrine factor‐secreting abilities. However, certain points regarding conventional ADSC delivery systems, such as low cell density, secreted cytokine levels, and cell viability, still need to be addressed for treating severe wounds. In this study, we developed a three‐dimensional (3D) cavity‐structured stem cell‐laden system for overdense delivery of cells into severe wound sites. Our system includes a hydrophobic surface and cavities that can enhance the efficiency of cell delivery to the wound site. In particular, the cavities in the system facilitate hADSC spheroid formation, increasing therapeutic growth factor expression compared with 2D cultured cells. Our hADSC spheroid‐loaded patch exhibited remarkably improved cell localization at the wound site and dramatic therapeutic efficacy compared to the conventional cell injection method. Taken together, the hADSC spheroid delivery system focused on cell delivery, and stem cell homing effect at the wound site showed a significantly enhanced wound healing effect. By overcoming the limitations of conventional cell delivery methods, our overdense cell delivery system can contribute to biomedical and clinical applications.