A Comparative Study of the Bone Marrow- and Umbilical Cord-Derived Mesenchymal Stem Cells (MSCs) Efficiency on Generating MSC-Educated Macrophages (MEMs)

BACKGROUND: Mesenchymal stem cells (MSCs) have gained much more attention in cell therapy and regenerative medicine due to their immunosuppressive effects. MSCs have interaction with other immune cells, such as macrophages (MQs). Bone marrow (BM)-derived MSCs can educate MQs toward MSC-educated MQs (MEMs) which possess an anti-inflammatory immunophenotype. Given this and based on the important limitations of BM collection, we hypothesized whether co-culture of MQs with umbilical cord (UC)-derived MSCs can result in the MEM phenotype. METHODS: First, isolated monocytes cultured for five days to obtain M0 MQs. Then, they were co-cultured with either BM- or UC-MSCs under direct and indirect conditions. After three days of co-culture, MEM-specific surface markers, as well as the gene expression of inflammatory and anti-inflammatory cytokines, were evaluated. RESULTS: Surface expression of CD163/CD206, as specific markers for M2 MQs, increased in MEMs after co-culture with BM- and UC-derived MSCs, while CD80/CD86 expression (specific markers for M1 MQs) didn’t change significantly. The mRNA expressions of PDL-1 as well as anti-inflammatory cytokines, including IL-6, IL-10, and TGFβ also increased in MEMs after co-culture of UC-MSCs compared to control MQs (p <.05), while the expression of IL-12 was significantly decreased (p<.001). CONCLUSIONS: To the best of our knowledge, this study shows for the first time that the co-culture of MQs with UC-derived MSCs efficiently contributes to the generation of MEMs even greater than BM-MSCs; shedding light on the promising potential of UC as an alternative source to educate MQs in vitro.