Women with hypertensive disorders of pregnancy have an increased risk of subsequent heart failure and cardiovascular disease when compared with women with normotensive pregnancies. Although the mechanisms underlying these findings are unclear, elevated levels of the biomarker activin A are associated with myocardial dysfunction and may have predictive value. We hypothesized that elevated levels of antepartum activin A levels would correlate with postpartum cardiac dysfunction in women with hypertensive disorders of pregnancy. We prospectively studied 85 women to determine whether increased antepartum activin A levels were associated with cardiac dysfunction at 1 year postpartum as measured by global longitudinal strain. Thirty-two patients were diagnosed with preeclampsia, 28 were diagnosed with gestational or chronic hypertension, and the remainder were nonhypertensive controls. Activin A levels were measured with ELISA both in the third antepartum trimester and at 1 year postpartum. Comprehensive echocardiograms including measurement of global longitudinal strain were also performed at enrollment and at 1 year postpartum. Antepartum activin A levels correlated with worsening antepartum global longitudinal strain (=0.70; =0.0001). Across the entire cohort, elevated antepartum activin A levels were associated with the development of abnormal global longitudinal strain at 1 year (C statistic 0.74;=0.004). This association remained significant after multivariable adjustment for clinically relevant confounders (C statistic 0.93; =0.01). Postpartum activin A levels also correlated with increasing left ventricular mass index (=0.02), increasing mean arterial pressures (=0.02), and decreasing E' values (=0.01). Activin A may be a useful tool for identifying and monitoring patients at risk for postpartum development of cardiovascular disease.

Hormone replacement therapies have become important for treating diseases such as premature ovarian failure or menopausal complications. The clinical use of bioidentical hormones might significantly reduce some of the potential risks reportedly associated with the use of synthetic hormones. In the present study, we demonstrate the utility and advantage of a microfluidic chip culture system to enhance the development of personalized, on-demand, treatment modules using embryoid bodies (EBs). Functional EBs cultured on microfluidic chips represent a platform for personalized, patient-specific treatment cassettes that can be cryopreserved until required for treatment. We assessed the viability, differentiation, and functionality of EBs cultured and cryopreserved in this system. During extended microfluidic culture, estradiol, progesterone, testosterone, and anti-müllerian hormone levels were measured, and the expression of differentiated steroidogenic cells was confirmed by immunocytochemistry assay for the ovarian tissue markers anti-müllerian hormone receptor type II, follicle-stimulating hormone receptor, and inhibin b-A and the estrogen biosynthesis enzyme aromatase. Our studies showed that under microfluidic conditions, differentiated steroidogenic EBs continued to secrete estradiol and progesterone at physiologically relevant concentrations (30-120 pg/ml and 150-450 pg/ml, respectively) for up to 21 days. Collectively, we have demonstrated for the first time the feasibility of using a microfluidic chip system with continuous flow for the differentiation and extended culture of functional steroidogenic stem cell-derived EBs, the differentiation of EBs into cells expressing ovarian antigens in a microfluidic system, and the ability to cryopreserve this system with restoration of growth and functionality on thawing. These results present a platform for the development of a new therapeutic system for personalized medicine. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:261-268

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Preeclampsia-related morbidity and mortality is rising predominantly because of delayed identification of patients at risk for preeclampsia with severe features and associated complications. This study explored the association between angiogenic markers (sFlt1 [soluble fms-like tyrosine kinase-1]) and PlGF [placental growth factor]) and preeclampsia-related peripartum complications. Normotensive women or those with hypertensive disorders of pregnancy were enrolled. Blood samples were collected within 96 hours before delivery, and angiogenic markers were measured on an automated platform. Our study included 681 women, 375 of which had hypertensive disorders. Of these, 127 (33.9%) had severe preeclampsia, and 71.4% were black. Compared with normotensive women, women with severe preeclampsia had higher levels of sFlt1 (9372.5 versus 2857.0 pg/mL; P <0.0001), lower PlGF (51.0 versus 212.0 pg/mL; P <0.0001), and a high sFlt1/PlGF (212.0 versus 14.0; all P <0.0001). A similar trend in sFlt1, PlGF, and sFlt1/PlGF was found in those women with complications secondary to preeclampsia (all P <0.001). The highest tertile of sFlt1/PlGF was strongly associated with severe preeclampsia in a multivariable analysis. Among patients with a hypertensive disorder of pregnancy, 340 (90.7%) developed postpartum hypertension, of which 50.4% had mild, and 40.3% had severe postpartum hypertension. The sFlt1/PlGF ratio was significantly higher for severe and mild postpartum hypertension compared with women with normal postpartum blood pressures (73.5, 46.0, and 13.0, respectively; P values<0.0001). Furthermore, the highest tertile of antepartum sFlt1/PlGF was associated with postpartum hypertension ( P =0.004). This study demonstrates a significant association between an abnormal angiogenic profile before delivery and severe preeclampsia and peripartum complications.