Shaping vessels and microenvironment: adipose stromal cells in retinal-related diseases

Diabetes causes several complications in the body. In this thesis, we focused on diabetic retinopathy. Retinopathy affects primarily the microcirculation in the retina. Subsequently, more retinal cellular constituents become sensitive to the glucose imbalanced. A possible solution is to implement the retinal microenvironment with stem cells. Stem cells, specifically adipose stromal cells (ASC), could potentially be integrated in the eyes to restore the damaged caused by diabetes. ASC function as supporting cells, in other words, microvessels damaged by glucose can be reinforced by injection of autologous ASC. The aim of this work was to understand which mechanisms are involved in the ASC potential to restore damaged microenvironments and therefore, improve stem cells therapy. We found that notch signaling is involved in ASC communication with microvessels. Microvessels have a fundamental role in giving nutrients and protection to the delicate retinal microenvironment. From this study, we concluded that future work on notch signaling could improve stem cells integration in the retina. This thesis includes a review which the complexity of diabetic retinopathy is further analyzed. Inflammation plays also a role in the developing of the disease and need to be considered for potential human trials. In the second part of the manuscript, temporal dynamics of ASC and microvessels formation and assembly were studied in three-dimensional cultures in vitro. We proposed a step by step formation of microvessels guided by ASC including extracellular matrix formation. Future research on stem cells therapy should include cells metabolism and extracellular matrix involvement during the disease progression.