Carlos Salomon Gallo

The Role of Placental Exosomes in Gestational Diabetes Mellitus

Gestational Diabetes Mellitus (GDM) affects ~5% of all pregnancies and parallels the global increase in obesity and type 2 diabetes. In the USA alone, GDM affects more than 135,000 pregnancies per year. Lifestyle changes that impact adversely on caloric balance are thought to be a contributing factor in this emerging pandemic (Ferrara, Kahn et al. 2004; Robitaille and Grant 2008). The current ‘gold standard’ for the diagnosis of GDM is the oral glucose tolerance test (OGTT) at 24–28 weeks of gestation (Salomon, Westermeier et al. 2012). When GDM is diagnosed in the late second or early third trimester of pregnancy the ‘pathology’ is most likely well-established and the possibility to reverse or limit potential adverse effect on perinatal outcomes may be limited (Agarwal, Weigl et al. 2011). Early detection of predisposition to and/or onset of GDM, thus, is the first step in developing, evaluating and implementing efficacious treatment. If such early detection tests were available, they would represent a major advance and contribution to the discipline and afford the opportunity to evaluate alternate treatment and clinical management strategies to improve health outcomes for both mother and baby. Based upon recent technological developments and studies, we consider it realistic that a clinically useful antenatal screening test can be developed. Unlike diseases such as cancer where biomarkers need to be exquisitely specific, a useful antenatal screening test would ideally be highly sensitive, but not necessarily highly specific. The consequence of a false positive would be no worse than an erroneous triage to high-risk care.

Recent studies highlight the putative utility of tissue-specific nanovesicles (e.g. exosomes) in the diagnosis of disease onset and treatment monitoring (Taylor and Gercel-Taylor 2005; Armitage, Poston et al. 2008; Simpson, Jensen et al. 2008; Atay, Gercel-Taylor et al. 2011; Atay, Gercel-Taylor et al. 2011; Chen, Ge et al. 2012). To date there is a paucity of data defining changes in the release, role and diagnostic utility of placenta-derived nanovesicles (e.g. exosomes) in pregnancies complicated by GDM.

Extracellular vesicles and ovarian cancer

Ovarian cancer (OC) is one of the most diagnosed gynecological cancers in women. Due to the lack of effective early stage screening, women are more often diagnosed at an advanced stage; therefore, it is associated with poor patient outcomes. There are a lack of tools to identify patients at the highest risk of developing this cancer. Moreover, early detection strategies, therapeutic approaches, and real-time monitoring of responses to treatment to improve survival and quality of life are also inadequate. Tumor development and progression are dependent upon cell-to-cell communication, allowing cancer cells to re-program cells not only within the surrounding tumor microenvironment, but also at distant sites. Recent studies established that extracellular vesicles (EVs) mediate bi-directional communication between normal and cancerous cells. EVs are highly stable membrane vesicles that are released from a wide range of cells, including healthy and cancer cells. They contain tissue-specific signaling molecules (e.g., proteins and miRNA) and, once released, regulate target cell phenotypes, inducing a pro-tumorigenic and immunosuppressive phenotype to contribute to tumor growth and metastasis as well as proximal and distal cell function. Thus, EVs are a "fingerprint" of their cell of origin and reflect the metabolic status. Additionally, via the capacity to evade the immune system and remain stable over long periods in circulation, EVs can be potent therapeutic agents.