Chao-Nin Wang

Functional Network Analysis of the Transcriptomes of Mesenchymal Stem Cells Derived from Amniotic Fluid, Amniotic Membrane, Cord Blood, and Bone Marrow

Using high‐density oligonucleotide microarrays and functional network analyses, we examined whether MSCs derived from four different origins exhibited unique gene expression profiles individually and then compared the gene expression profiles of all MSCs with those of fetal organs. Our results indicated that within each group of MSCs from the same origin, the variability of the gene expression levels was smaller than that between groups of different origins. Functional genomic studies revealed the specific roles of MSCs from different origins. Our results suggest that amniotic fluid MSCs may initiate interactions with the uterus by upregulating oxytocin and thrombin receptors. Amniotic membrane MSCs may play a role in maintaining homeostasis of fluid and electrolytes by regulating the networks of endothelin, neprilysin, bradykinin receptors, and atrial natriuretic peptide. Cord blood MSCs may be involved in innate immune systems as the neonatal defense system against the earliest encountered pathogens. Adult bone marrow MSCs may be an important source not only of all blood lineages but also of bone formation. However, in spite of the different gene expression profiles seen in MSCs derived from different origins, a set of core gene expression profiles was preserved in these four kinds of MSCs. The core signature transcriptomes of all MSCs, when contrasted against those of fetal organs, included genes involved in the regulation of extracellular matrix and adhesion, transforming growth factor‐β receptor signaling, and the Wnt signaling pathways.

Clinical outcome and placental territory ratio of monochorionic twin pregnancies and selective intrauterine growth restriction with different types of umbilical artery Doppler

To evaluate the clinical outcome and placental territory ratio in monochorionic diamniotic (MCDA) twin pregnancies and selective intrauterine growth restrictions (sIUGR) with different types of umbilical artery (UA) Doppler.

Change in amniotic fluid levels of multiple anti-angiogenic proteins before development of preeclampsia and intrauterine growth restriction.

CONTEXT The cause of preeclampsia remains unknown. Excessive antiangiogenic proteins have been proposed to play a pathogenic role in preeclampsia. OBJECTIVE Our objective was to determine the differences in soluble endoglin (sEndoglin), soluble fms-like tyrosine kinase receptor-1 (sFLT1), leptin, adiponectin, and endothelin 1 concentrations between normal and preeclampsia amniotic fluid (AF). Such results may help us understand the pathophysiology of preeclampsia. METHODS We performed a nested case-control study. Seventy-one women with preeclampsia were matched to 71 normotensive controls. The preeclamptic women were broken into two subgroups according to the association with fetal intrauterine growth restriction (IUGR). AF concentrations of sEndoglin, sFLT1, leptin, adiponectin, and endothelin 1 were measured by ELISA. Receiver-operating characteristics curve analysis was used to compare the discriminative values of these potential biomarkers. Functional network analysis was performed using MetaCore to reveal the common functions of the interacting proteins. RESULTS Increased AF concentrations of sFLT1, sEndoglin, endothelin 1, and leptin were found in women who later developed preeclampsia. sFLT1, sEndoglin, leptin, and adiponectin were significantly higher in the preeclampsia with IUGR than those without IUGR. Leptin has the largest area under the curve (0.753). Network analysis revealed that elevated amniotic proteins are involved in the inflammatory process of the human placenta. CONCLUSIONS Significant elevation of leptin can be detected in AF 2 months earlier than the appearance of symptoms; thus, it may be used as a predictive marker for preeclampsia. The increase of these antiangiogenic proteins supports the roles of inflammation and oxidative stress in pathogenesis of preeclampsia.

MicroRNA and Messenger RNA Analyses of Mesenchymal Stem Cells Derived from Teeth and the Wharton Jelly of Umbilical Cord

Microarray analyses of transcriptomes have been used to characterize mesenchymal stem cells (MSCs) of various origins. MicroRNAs (miRNAs) are short, nonprotein-coding RNAs involved in post-transcriptional gene inhibition in a variety of tissues, including cancer cells and MSCs. This study has integrated the use of miRNA and mRNA expression profiles to analyze human MSCs derived from Whartons jelly (WJ) of the umbilical cord, milk teeth (MT), and adult wisdom teeth (AT). Because both miRNA and mRNA expression in MT and AT MSCs were so similar, they were combined together as tooth MSCs for comparison with WJ MSCs. Twenty-five genes that were up-regulated in tooth MSCs and 41 genes that were up-regulated in WJ MSCs were identified by cross-correlating miRNA and mRNA profiles. Functional network analysis show that tooth MSCs signature genes, represented by SATB2 and TNFRSF11B, are involved in ossification, bone development, and actin cytoskeleton organization. In addition, 2 upregulated genes of tooth MSCs-NEDD4 and EMP1-have been shown to be involved in neuroectodermal differentiation. The signature genes of WJ MSCs, represented by KAL1 and PAPPA, are involved in tissue development, regulation of cell differentiation, and bone morphogenetic protein signaling pathways. In conclusion, the combined interrogation of miRNA and mRNA expression profiles in this study proved useful in extracting reliable results from a genome-wide comparison of multiple types of MSCs. Subsequent functional network analysis provided further functional insights about these MSCs.

The individual fetal weight/estimated placental weight ratios in monochorionic twins with selective intrauterine growth restriction.

To evaluate the individual fetal weight/estimated placental weight ratios (F/P ratio) of the two fetuses in monochorionic (MC) twins with selective intrauterine growth restriction (IUGR).

Elevated amniotic fluid F2-isoprostane: A potential predictive marker for preeclampsia

In the complex mechanism of preeclampsia, oxidative stress is an important pathogenic factor, and F₂-isoprostane is a marker of oxidative stress and lipid peroxidation. The objective of this study was to identify if the amniotic fluid (AF) levels of F₂-isoprostanes were elevated in women who later developed preeclampsia. In this study, we analyzed AF F₂-isoprostane concentrations with enzyme immunoassay (EIA), and the EIA results could be validated by quantitative mass spectrometry. The mean AF concentration of F₂-isoprostanes was significantly higher in pregnancies with subsequent development of preeclampsia (123.1 ± 57.6 pg/ml, n = 85) than in controls (73.8 ± 36.6 pg/ml, n = 85). The AF elevation of F₂-isoprostanes was even higher in the preeclampsia with intrauterine growth restriction group (138.3 ± 65.2 pg/ml, n = 39). The area under the curve of the receiver operating characteristics analysis for AF F₂-isoprostanes assay was 0.81, supporting its potential as a biomarker for preeclampsia. These results indicate that oxidative stress existed before the onset of clinical preeclampsia, further suggesting that the elevation of AF F₂-isoprostanes may be used as a guide for antioxidant supplementation to reduce the risk and/or severity of preeclampsia.

Increased autophagy in the placental territory of selective intrauterine growth-restricted monochorionic twins

This study investigates the placental autophagic activity in growth‐restricted fetuses in the monochorionic (MC) twin model.

The neurological outcomes of surviving twins in severe twin–twin transfusion syndrome treated by fetoscopic laser photocoagulation at a newly established center

To evaluate the incidence and predictive factors of poor neurological outcome in survivors of twin‐to‐twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP).

Short-term outcomes of fetoscopic laser surgery for severe twin–twin transfusion syndrome from Taiwan single center experience: Demonstration of learning curve effect on the fetal outcomes

OBJECTIVE To evaluate the learning curve effect on fetal outcomes while using fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS) as managed by a newly established single center in Taiwan. MATERIALS AND METHODS Between October 2005 and October 2010, women diagnosed to have TTTS before 26 weeks of gestation were offered FLP surgery. Cases were divided into first-half and second-half groups to evaluate the learning effect on fetal outcomes including at least one survival rate, two survival rate, and gestational age of delivery. RESULTS A total of 44 cases with a median gestational age of 20.1 weeks (range 16-25) at operation were included in the study. Overall, both twins survived in 22 (50.0%) cases, whereas only one twin was born alive in 13 (29.5%), and neither was born alive in the remaining nine cases (20.5%). The total survival rate was 64.8%. When comparing the first-half 22 cases and the second-half 22 cases, there were significant improvements in total survival rate (54.7% vs. 75.0%, p = 0.045), a prolonged interval between operation and delivery (62.1 vs. 89.1 days, p = 0.042), and more advanced gestational age of delivery (28.3 vs. 33.0 weeks, p = 0.008) in the second-half 22 cases. CONCLUSIONS With increasing experience in using fetoscopic guide laser therapy for TTTS, the fetal survival rate could be improved with advanced gestational age at delivery.

The Relationships of Umbilical Venous Volume Flow, Birthweight and Placental Share in Monochorionic Twin Pregnancies with and without Selective Intrauterine Growth Restriction

This study was conducted to investigate the relationship among umbilical venous volume flow, birthweight and placental share in monochorionic twins with or without selective growth restriction. Having excluded cases complicated with twin-to-twin transfusion syndrome and one co-twin suffering intrauterine fetal death, a total of 51 monochorionic twin pregnancies were divided into two groups as with (group 1) and without (group 2) selective intrauterine growth restriction. Umbilical venous volume flow was calculated by multiplying the umbilical vein cross-sectional area by half of the maximal velocity around mid-trimester. The placentas were cut along the vascular equator into two individual placental masses. The discordance of birthweight was calculated as [(birthweight of larger twin-birthweight of smaller twin)/birthweight of larger twin 100%]. The discordances of umbilical venous volume flow and placental share were calculated in a similar fashion. The median umbilical venous volume flow discordances (68.4% and 15.3% in groups 1 and 2 monochorionic twins, respectively) were similar and correlated well with the placental share discordances (66.6% and 18.5% in groups 1 and 2 monochorionic twins, respectively) but not with the birthweight discordance (28.6% and 6.4% in groups 1 and 2 monochorionic twins, respectively) in both groups. We concluded that the umbilical venous volume flow discordance reflects the placental share discordance rather than the birthweight discordance in monochorionic twin pregnancies.