Influences of umbilical cord mesenchymal stem cells and their exosomes on tumor cell phenotype

Resumen

Backgrounds: Umbilical cord mesenchymal stem cells (UCMSCs) are derived from umbilical cord tissue. Due to their low immunogenicity, easy availability, mature culture technology, and lack of ethical controversy, they have gradually emerged as a focal point in stem cell research. Exosomes are cell-derived vesicles with a structure consistent with the cell membrane, primarily functioning as carriers to transport substrates for intercellular communication and regulation. Presently, both stem cells and their exosomes have emerged as highly promising biopharmaceuticals widely utilized in various clinical studies, including wound healing, spinal cord injury, post-operative rehabilitation, neurological disorders, and autoimmune diseases. However, the safety of these biologics remains uncertain, with some studies suggesting the potential tumorigenicity of stem cells and their exosomes. The objective of this study was to investigate the effects of UCMSCs and their exosomes on four types of tumor cells. Methods: In this study, first of all, UCMSCs and their exosomes were isolated and characterized. Subsequently, the study was performed in cell experiments. The effects of UCMSCs and their exosomes on four types of tumor cells (blast cancer cell line, gastric cancer cell line, glioma cell line, lung cancer cell line) were observed through co-culture experiments. The observables included the effects on in vitro phenotype and in vivo growth characteristics. Changes in gene expression were analyzed using high-throughput sequencing technology to elucidate the biological functions and roles of UCMSCs and their exosomes on tumor cells. Results: UCMSCs were successfully isolated, cultured, and identified. They demonstrated the capacity for differentiation into adipocytes, osteoblasts, chondrocytes, and neuron-like cells, indicating their multi-lineage differentiation potential. The UCMSCs-exos exhibited a diameter ranging from 30 to 150 nm, with an average size of 126.62 ± 1.64 nm, and showed increased expression of Tsg101, CD9, and CD63 proteins (P < 0.05). In cell experiments, the intervention of UCMSCs and UCMSCs-exos led to increased invasion and migration of MDA-MB-231 and BGC-823 cells (P < 0.05). A549 cells displayed enhanced migratory capacity (P < 0.05) with minimal change in invasiveness, while LN-229 cells exhibited suppressed activity (P < 0.05). Molecular experiments revealed no significant difference in ROS, MDA, and SOD assays between the primary cells, UCMSCs group, and UCMSCs-exos group (P > 0.05). However, in LN-229 cells, ROS and MDA levels were reduced, and SOD levels were increased in the UCMSCs group compared to the UCMSCs-exos group (P < 0.05). Furthermore, UCMSCs and UCMSCs-exos did not affect the expression of NF-B and p53 proteins in MDA-MB-231, BGC-823, and A549 cells (P > 0.05). In contrast, they inhibited the expression of NF-B and p53 proteins in LN-229, with UCMSCs-exos demonstrating a more pronounced inhibitory effect (P < 0.05). Conclusions: In conclusion, this study successfully isolated UCMSCs and their exosomes. They promote the proliferation, migration, and invasion of four types of tumor cells involves altering the cell cycle. Additionally, UCMSCs and their extracellular vesicles are influenced by oxidative stress, and the NF-B/P53 signaling pathway is implicated. These findings provide preliminary evidence that stem cells and their exosomes may not be suitable for patients with tumor diseases, offering an experimental basis for the potential clinical application safety of this technology in treatment.