In recent years, anti-angiogenic therapeutic agents (anti-VEGF) have contributed to the treatment of retinal vein occlusion (RVO). At the same time, Mesenchymal Stromal Cells (MSCs) secretory agents protect the ganglion cells, limiting eye degeneration. An in vitro model to evaluate medicines that may be effective in RVO therapy is missing. In an attempt to evaluate such a model, MEK kinase inhibitor-PD0325901 was used to induce the expression of EPCR (Endothelial Protein C Receptor) on HUVEC (Human Umbilical Cord Endothelial Cell) culture. Anti-VEGF encapsulated in thiolated chitosan (ThioCHI) nanoparticles, MSCs and a combination of these was applied to the cultures and their effect was monitored. Net nanoparticles of CHI and ThioCHI were prepared by ionic gelation technique while ThioCHI was selected as polymeric matrix for anti-VEGF encapsulation. Their full characterization was followed using Fourier-transform infrared spectroscopy, Differential scanning calorimetry and X-ray diffraction. MSCs were prepared from human adipose tissue liposuction cultured up to five passages. Following 24- hour exposure of HUVEC to PD0325901, the effect of anti-VEGF nanoparticles, MSCs, and a combination of these was assessed by quantifying the secreted EPCR and time-controlled anti-VEGF release using a commercial ELISA assay. The modified prepared nanoparticles showed no cytotoxic effect while antibody release was constant for 8 days. The abnormal EPCR levels were statistically significantly reduced after 24 and 48 hours following exposure of the abnormal endothelium either to the anti-VEGF nanoparticles or to MSCs. A combination of both agents was more effective than either agent separately on 24 hours. The expression of EPCR on PD0325901 induced HUVEC cultures may be used as a novel in vitro-RVO simulation model to test the efficacy of pharmaceuticals and other therapeutics, on RVO, reducing the animal cost for such experiments. Using this model anti-VEGF ThioCHI nanoparticles, MSCs and a combination of these agents have been positively evaluated.