An investigation of the biological mechanisms initiated in wounded skin following application of mesenchymal stem cells (MSCs) and nanoparticles (NPs) (Ag, ZnO), alone or combined, was performed in mice, with the aim to determine the most optimal approach to accelerate the healing processes. The samples were collected seven days after injury. When compared with the wounded untreated animals (controls), combined (MSCs+NPs) treatment induced the expression of Sprr2b, encoding Small proline-rich protein 2B, which is involved in keratinocyte differentiation, response to tissue injury and inflammation. The pathways associated with keratinocyte differentiation were also affected. Ag NP treatment (alone or combined) modulated the DNA methylation changes in the genes involved in desmosome organization. The percentage of activated regulatory macrophages at the wound site was increased by the MSC and Ag alone treatment, while the production of nitric oxide, an inflammatory marker, by stimulated macrophages was decreased by MSCs/Ag alone and MSCs+Ag treatment. Ag induced the expression of Col1, encoding collagen-1, at the injury site. In summary, MSC and NP treatment of skin wounds (alone or combined) suggests induction of the processes accelerating the proliferative phase of healing; MSCs-NP interactions are a key factor affecting global mRNA expression changes in the wound.