Mesenchymal stromal cells isolated from gestationally diabetic human placenta exhibit insulin resistance, decreased clonogenicity and angiogenesis

Pregnancy is known to be a diabetogenic state. With sedentary lifestyle and wrong dietary choices, gestational diabetes mellitus is on the rise. This raises a concern as placenta is becoming an acceptable choice, as a source of Mesenchymal Stromal Cells (MSCs). In our current study we questioned whether there exists a difference between MSCs isolated from normal and diabetic (Gd-P-MSCs) placenta, as the health of the cells used in therapy is of prime importance. We isolated and verified the Gd-P-MSCs based on their surface markers and differentiation potential. We looked at viability and proliferation and did not see a difference between the two. We analysed the glucose uptake potential of these cells by assessing the remnant glucose in the media, glucose within the cells by 2-NBDG and by glycogen storage. Despite only a slight downregulation of mRNA expression levels of glucose transporters, Gd-P-MSCs exhibited decreased glucose uptake even upon insulin stimulation and decreased glycogen storage, indicative of an insulin resistant state. We then assessed the colony forming ability of the cells and found a decreased clonogenicity in Gd-P-MSCs. We also examined the angiogenic potential of the cells by tube formation. Gd-P-MSCs showed decreased angiogenic potential when compared to normal cells. Thus we show for the first time, the effect of gestational diabetes on cells isolated from the chorionic villi of term placenta. Gd-P-MSCs are indeed insulin resistant, exhibit decreased clonogenicity and angiogenic potential. The present investigation is of relevance to the choice of sample for MSC isolation for therapeutic purposes.