It takes two to form a functional blood vessel - the endothelial cell and the perivascular supporting cell; - the pericyte, in the microvasculature. Pericyte abnormalities is key to  the pathogenesis of Adult Type 2 diabetic retinopathy. Despite several animal models of Diabetes, it is frustrating that none of them consistently reproduce adult human Type 2 proliferative retinopathy. Furthermore, the long term evaluation of vascular progenitor cells in Diabetes and vascular tissue engineering remains challenging, necessitating biologically relevant animal models and sophisticated imaging tools.

 

In India, 20-70% of Gestational Diabetes Mellitus (GDM) women and new borns will develop T2D post partum. We isolated and characterized foetal endothelial progenitor cells and pericytes from GDM and healthy women from South India.  Transmission Electron Microscopy demonstrated pericyte ghosts, increased micro vessel density and thickening of capillary basement in healthy placentas (p ≤ 0.001). Endothelial cell irregularity was noted in 76% GDM vs. 10.4% healthy placentas (p ≤ 0.001). Placental fetal GDM -EPCs and pericytes showed functional abnormalities and when implanted in subcutaneous matrigel plugs in SCID mice, as compared with healthy control placental EPCs and pericytes. We demonstrate in particular a unique placental phenotype in South Indian women. We believe that certain angiogenic and other molecular cues may be responsible for the particular phenotype observed in placental vascular progenitor cells.

The GDM placenta is a research tool that enhances our understanding of pathophysiology and molecular signatures of Adult Type 2 Proliferative Diabetic Retinopathy, and the cross talk between diabetic endothelial cells and pericytes. A combination of genetic, epigenetic and environmental factors is responsible for in utero reprogramming that results in the development of diseases in later life such as Type 2 Diabetes. We stipulate that adult diabetic vascular disease might also be influenced by the intrauterine hyperglycemic milieu.