Application of Tissue Engineering and Regenerative Medicine in Maternal-Fetal Medicine.

A rapid development of ultrasonography has enabled physicians to make earlier prenatal diagnosis of various fetal congenital diseases, in maternal-fetal medicine. Due to the significant mortality and irreversible damage to fetal vital organs during pregnancy, fetal surgeries have been tried in some congenital disease including congenital diaphragmatic hernia, twin-to-twin transfusion syndrome (TTTS), myelomeningocele (MMC), and lower urinary tract obstruction. However, open fetal surgery requires laparotomy followed by hysterotomy, which can cause preterm premature rupture of membrane (pPROM), oligohydramnios, preterm delivery, dehiscence of uterine wall, and other maternal complications during pregnancy. Minimally invasive approach using fetoscopy has been tried, and fetoscopic laser photocoagulation of vascular communications is currently considered as a treatment of choice for TTTS before 26 weeks' gestation. However, more development of surgical instrument and innovative materials using tissue engineering are required to improve outcomes of fetoscopic surgery. Because iatrogenic pPROM is the major challenge after fetoscopic surgery, this review focuses on current development of materials for treatment of spontaneous or iatrogenic pPROM and recent experimental progress of tissue engineering-based technology in prenatal treatment of MMC. Placental tissue is an emerging material for regenerative medicine. This chapter will also review regenerative potential and experiments of placenta and placenta-derived stem cells, as well as prospects of "in utero stem cell therapy."

The Educational Effects of a Pregnancy Simulation in Medical/Nursing Students and Professionals.

BACKGROUND: The objective of this study was to investigate whether a pregnancy experience program (PREP) simulating physical changes in a mother during the last trimester of pregnancy could increase empathy, understanding, and positive attitude of medical/nursing students and their professional counterparts. METHODS: This was a prospective observational study on medical/nursing students and their professional counterparts. Jefferson Scale of Physician Empathy (JSPE), physical difficulty and positive attitude score, and perceived effectiveness scores prior to PREP were compared to those after PREP. RESULTS: A total of 189 participants completed PREP and questionnaires both prior to and after PREP. Mean JSPE score, physical difficulty score, and positive attitude scores were significantly increased following PREP (p<0.001, all). Perceived effectiveness scores about awareness, empathy, and understanding after PREP were significantly high in the professional group than in the student group (p=0.004, p=0.01, and p=0.017, respectively). Multiple stepwise linear regression analysis revealed that major in medicine (p = 0.014), health care professionals (nurse or physician) (p<0.001), and marriage experience (p < 0.001) were significant predictors of increasing empathy, difficulty feelings and effectiveness scores, respectively. CONCLUSION: PREP is an effective simulation program that can improve empathy, positive attitude, and awareness in medical/nursing students as well as their professional counterparts.

Efficacy and safety of ferric carboxymaltose versus ferrous sulfate for iron deficiency anemia during pregnancy: subgroup analysis of Korean women.

BACKGROUND: We performed a post-hoc subgroup analysis in Korean women who participated in the Phase III FER-ASAP (FERric carboxymaltose-Assessment of SAfety and efficacy in Pregnancy) study to compare the efficacy and safety of ferric carboxymaltose (FCM) with oral ferrous sulfate (FS). METHODS: Pregnant Korean women (gestational weeks 16-33) with iron-deficiency anemia (IDA) were randomized 1:1 to FCM (n = 46; 1000-1500 mg iron) or FS (n = 44; 200 mg iron/day) group for 12 weeks. The primary objective was to compare the mean hemoglobin (Hb) increase at week 3; secondary objectives included change in iron parameters, quality of life (QoL), and safety. RESULTS: Baseline characteristics of the Korean subgroup were consistent with those of non-Korean FER-ASAP population except for lower body-mass index and higher maternal age. Hb level increases were comparable between the two treatment groups in Korean women at week 3 (FCM 1.23 ± 0.89 g/dL vs FS 1.14 ± 1.72 g/dL). Iron parameters improved over time as secondary endpoints were significantly in favor of FCM. In terms of QoL, FCM treatment significantly improved the mental and physical components as well as vitality prior to delivery. Both treatments were well tolerated. CONCLUSIONS: FCM provided significantly greater improvements in iron parameters and QoL compared to FS in the Korean subgroup. FCM may be a preferable alternative to currently available treatments for IDA during pregnancy.

Optimal Timing of Delivery Based on the Risk of Stillbirth and Infant Death Associated with Each Additional Week of Expectant Management in Multiple Pregnancies: a National Cohort Study of Koreans.

BACKGROUND: The purpose of this study was to compare the fetal/infant mortality risk associated with each additional week of expectant management to that associated with immediate delivery in women with multiple gestations. METHODS: This was a retrospective national cohort study of 94,170 multiple deliveries, 92,619 (98.4%) twin and 1,352 (1.44%) triplet pregnancies, between 32 0/7 and 42 6/7 weeks of gestation recorded in the Korean vital statistics database. We investigated the risks of stillbirth and infant death after birth in Korea according to the week of gestation in twin and triplet pregnancies. RESULTS: The risk of stillbirth significantly increased between 34 and 35 weeks of gestation and between 37 and 38 weeks of gestation in twin pregnancies and between 34 and 37 weeks of gestation in triplet pregnancies. The risk of infant death following delivery gradually decreased as pregnancies approached full term. Week-by-week differences were statistically significant between 33 and 34 weeks, with decreasing risks of infant death at advancing gestational ages in twin pregnancies. At 37 weeks of gestation, the relative risk of mortality was significantly higher with expectant management compared with immediate delivery (relative risk, 3.00; 95% confidence interval, 1.41-6.38). CONCLUSION: In twin pregnancies, delivery at 37 weeks of gestation can minimize the risks of stillbirth and infant death in uncomplicated cases, although individual maternal and fetal characteristics must be considered when determining the optimal timing of delivery. In multiple pregnancies, close fetal surveillance is needed after 34 weeks of gestation.

Determining optimal gestational weight gain in the Korean population: a retrospective cohort study.

BACKGROUND: The World Health Organization (WHO) international body mass index (BMI) cut-off points defining pre-pregnancy BMI categories in the Institute of Medicine (IOM) guidelines are not directly applicable to Asians. We aimed to define the optimal gestational weight gain (GWG) for the Korean population based on Asia-specific BMI categories. METHODS: Data from 2702 live singleton deliveries in three tertiary centers between 2010 and 2011 were analyzed retrospectively. A multivariable logistic regression analysis was conducted to determine the lowest aggregated risk of composite perinatal outcomes based on Asia-specific BMI categories. The perinatal outcomes included gestational hypertensive disorder, emergency cesarean section, and fetal size for gestational age. In each BMI category, the GWG value corresponding to the lowest aggregated risk was defined as the optimal GWG. RESULTS: Among the study population, 440 (16.3%) were underweight (BMI < 18.5), 1459 (54.0%) were normal weight (18.5 ≤ BMI < 23), 392 (14.5%) were overweight (23 ≤ BMI < 25) and 411 (15.2%) were obese (BMI ≥ 25). The optimal GWG by Asia-specific BMI category was 20.8 kg (range, 16.7 to 24.7) for underweight, 16.6 kg (11.5 to 21.5) for normal weight, 13.1 kg (8.0 to 17.7) for overweight, and 14.4 kg (7.5 to 21.9) for obese. CONCLUSION: Considerably higher and wider optimal GWG ranges than recommended by IOM are found in our study in order to avoid adverse perinatal outcomes. Revised IOM recommendations for GWG could be considered for Korean women according to Asian BMI categories. Further prospective studies are needed in order to determine the optimal GWG for the Korean population.

Contribution of Magnetic Resonance Imaging to Ultrasound for the Evaluation of Fetal Central Nervous System Anomalies.

OBJECTIVE: To evaluate whether magnetic resonance imaging (MRI) contributes to ultrasound for the evaluation of fetal central nervous system (CNS) anomalies. The secondary objective was to investigate whether MRI adds more information regarding the evaluation of specific pathologies or conditions. STUDY DESIGN: We retrospectively compared fetal MRI findings with ultrasound findings in CNS anomalies with respect to certain pathologic groups. Additionally, we evaluated diagnostic accuracy by comparing fetal MRI and ultrasound findings with postnatal findings. RESULTS: A total of 34 patients had 40 provisional diagnoses by fetal ultrasound, and of those patients 14 had a provisional diagnosis of ventriculomegaly and 14 had a provisional diagnosis of cerebellar or posterior fossa anomalies. MRI added to or changed the diagnosis in 52.5% of the patients with CNS abnormalities. The contribution rate in ventriculomegaly was 71.4%, and MRI changed the diagnosis in all indefinite diagnoses by ultrasound. Additionally, of the 15 patients with postnatal findings, there were no cases in which only the ultrasound findings were correct, but the MRI findings were incorrect. CONCLUSION: MRI contributes to ultrasound in the diagnosis of CNS anomalies. Cases of indefinite diagnosis and ventriculomegaly by ultrasound had greater benefit from MRI.

Prevalence of Low Bone Mineral Density and Associated Risk Factors in Korean Puerperal Women.

Although pregnancy is a medical condition that contributes to bone loss, little information is available regarding bone mineral density (BMD) in puerperal women. This cross sectional study aimed to evaluate the prevalence of low BMD in puerperal women and to identify associated risk factors. We surveyed all puerperal women who had BMD measurements taken 4-6 weeks after delivery in a tertiary university hospital, and did not have any bone loss-related comorbidities. Among the 1,561 Korean puerperal women, 566 (36.3%) had low BMD at the lumbar spine, total hip, femoral neck, and/or trochanter. Multivariate analysis revealed that underweight women had a significantly higher risk of low BMD compared with obese women at pre-pregnancy (adjusted odds ratio [aOR], 3.21; 95% confidence interval [CI], 1.83-5.63). Also, women with inadequate gestational weight gain (GWG) were 1.4 times more likely to have low BMD than women with excessive GWG (aOR, 1.42; 95% CI, 1.04-1.94). One-way ANOVA showed that BMDs at the lumbar spine and total hip were significantly different between the 4 BMI groups (both P < 0.001) and also between the 3 GWG groups (both P < 0.001). In conclusion, this study identifies a high prevalence of low BMD in puerperal women and thus suggests the need for further evaluation about the change of BMD in pregnancy and postpartum period.

Priming Wharton's jelly-derived mesenchymal stromal/stem cells with ROCK inhibitor improves recovery in an intracerebral hemorrhage model.

Mesenchymal stromal/stem cells (MSCs) have the potential to differentiate into neuron-like cells under specific conditions and to secrete paracrine factors for neuroprotection and regeneration. Previously, Rho-kinase inhibitors have been reported to potentiate differentiation of rodent bone marrow MSCs into neuron-like cells induced by CoCl2 (HIF-1α activation-mimicking agent). Here, a strategy of priming MSCs with fasudil, a Rho-kinase inhibitor, was investigated using Wharton's jelly-derived MSCs (WJ-MSCs) to improve recovery in a rat model of intracranial hemorrhage (ICH). In vitro culture of WJ-MSCs by co-treatment with fasudil (30 µM) and CoCl2 provoked morphological changes of WJ-MSCs into neuron-like cells and increased the expression of neuronal markers. Assessment of the secretion profiles showed that fasudil (30 µM) specifically increased glial cell line-derived neurotrophic factor (GDNF) among the secreted proteins at the transcription and secretion levels. For in vivo experiments, WJ-MSCs primed with fasudil (10 µM, exposure for 6 h) were transplanted into ICH rats with HIF-1α upregulation 1 week after injury, and neurological function was assessed via rotarod and limb placement tests for 7 weeks after transplantation. The group with WJ-MSCs primed with fasudil showed improved functional performance compared with the non-primed group. Accordingly, the primed group showed stronger expression of GDNF and higher levels of microtubule-associated protein 2 and neurofilament-H positive-grafted cells in the ICH lesion 3 weeks after transplantation compared with the non-primed group. Therefore, this work suggests that priming WJ-MSCs with fasudil is a possible application for enhanced cell therapy in stroke, with additional beneficial effect of up-regulation of GDNF.

Sonographic Parameters for Prediction of Miscarriage: Role of 3-Dimensional Volume Measurement.

OBJECTIVES: To evaluate the value of volume measurement using 3-dimensional sonography for prediction of miscarriage. METHODS: We prospectively enrolled 188 singleton pregnant women at 5 to 9 weeks' gestation. The 3-dimensional sonographic gestational sac volume and yolk sac volume were measured together with the fetal heart rate, gestational sac diameter, and yolk sac diameter. For each sonographic parameter, nomograms were created; z scores were calculated for each measurement, and the values were compared between miscarriage and ongoing pregnancy groups. Sonographic parameters for prediction of miscarriage were evaluated by multivariate analysis, and the screening performance was assessed by a receiver operating characteristic curve. RESULTS: Among the 188 pregnancies, 30 (16.0%) had miscarriage. Multivariate analysis showed that fetal heart rate below the 5th percentile (odds ratio, 6.43), gestational sac diameter below the 5th percentile (odds ratio, 4.87), gestational sac volume below the 5th percentile (odds ratio, 5.25), and yolk sac diameter below the 2.5th or above the 97.5th percentile (odds ratio, 15.86) were significant predictors of miscarriage (P = .018; P = .018; P = .033; and P < .001, respectively). At a false-positive rate of 30%, the detection rate for miscarriage in screening by a combination of fetal heart rate, gestational sac diameter, gestational sac volume, and yolk sac diameter was 77.8%. CONCLUSIONS: A small-for-gestational-age gestational sac volume is a significant sonographic predictor of miscarriage, as are fetal bradycardia, a small gestational sac diameter, and a small or large yolk sac diameter.

Effects of ECM protein mimetics on adhesion and proliferation of chorion derived mesenchymal stem cells.

BACKGROUND: We evaluated the effects of fibronectin, collagen, cadherin, and laminin based extracellular matrix (ECM) protein mimetics coated with mussel derived adhesive protein (MAP) on adhesion and proliferation of chorionic mesenchymal stem cells (cMSCs). METHODS: Human placental chorionic tissues from term third-trimester pregnancies (n=3) were used. The cMSCs were cultured on rationally designed ECM protein mimetics coated with MAP on plastic surfaces with the addition of reduced fetal bovine serum (0.5%, 1% FBS). Adhesion capabilities were monitored by a real time cell analysis system (RTCA) utilizing an impedance method. Proliferation capabilities were monitored by RTCA and MTS assay. RESULTS: Of the ECM protein mimetics tested, GRGDSP(FN) coated surfaces exhibited the highest adhesion and proliferation capabilities on RTCA at FBS concentration of 0.5% and 1%. When 0.5% FBS was added to ECM protein mimetics during the MTS assay, GRGDSP(FN), REDV(FN), and collagen mimetics, GPKGAAGEPGKP(ColI) showed higher cMSCs proliferation compared with the control. When 1% FBS was added, GRGDSP(FN) and TAIPSCPEGTVPLYS(ColIV) showed significant cMSCs proliferation capacity. CONCLUSIONS: Fibronectin mimetics, GRGDSP(FN) amino acid sequence showed the highest adhesion and proliferation capabilities. In addition, results from RTCA assessment of cell viability correlated well with the tetrazolium-based MTS assay.

Fetal biometry in the Korean population: reference charts and comparison with charts from other populations.

OBJECTIVE: The objectives of this article were to construct size charts for fetal biometry in the Korean population and to identify ethnic differences in fetal biometry. METHOD: A prospective, cross-sectional study was performed with 986 fetuses between 15 to 40 weeks of gestation. The following biometric variables were measured: biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and long bones lengths including the femur, tibia, humerus, and ulna. For each measurement, regression models were fitted to estimate the mean and standard deviation at each gestational age. The calculated centiles were compared with centiles from other populations using Z-scores. RESULTS: New charts for the Korean population were presented for the fetal biometric variables. Most of the parameters were similar to those for the Italian population. Also, in comparison with the North American and UK populations, Korean fetuses had greater BPD, HC, and AC in the first half of pregnancy but tended to measure progressively smaller with advancing gestational age. In comparison with the Hong Kong population, Korean fetuses had a longer femur length at any gestational age. CONCLUSION: We present size charts for fetal biometry for the Korean population using the recommended methodology, suggesting they are different from what is reported in other ethnicities.

Impact of antenatal depression on perinatal outcomes and postpartum depression in Korean women.

BACKGROUND: Maternal prenatal mental health has been shown to be associated with adverse consequences for the mother and the child. However, studies considering the effect of prenatal depressive symptoms are lacking. The aim of this study was to examine the influence of antenatal depressive symptoms on obstetric outcomes and to determine associations between antenatal and postpartum depressions. MATERIALS AND METHODS: This was a prospective cohort study. The Edinburgh postnatal depression scale (EPDS) questionnaire was completed by pregnant women receiving obstetrical care at Seoul St. Mary's hospital in the third trimester of gestation. The electronic medical records were reviewed after delivery and perinatal outcomes were evaluated. The association between antenatal and postpartum depression was analyzed using the EPDS questionnaire, which was completed by the same women within 2 months of delivery. RESULTS: Of the 467 participants, 26.34% (n = 123) had antenatal depressive symptoms, with EPDS scores of ≥10. There were no significant perinatal outcomes associated with antenatal depressive symptoms. During the postpartum period, 192 of the women in the initial study cohort were given the EPDS again as a follow-up. Of the 192 participants, 56 (29.17%) scored >10. Spearman correlation coefficient between the antenatal and postpartum EPDS scores was 0.604, which was statistically significant (P < 0.001). CONCLUSION: Antenatal depression does not lead to unfavorable perinatal outcomes. However, screening for antenatal depression may be helpful to identify women at risk of postpartum depression.

Oncostatin M stimulates cell migration and proliferation by down-regulating E-cadherin in HTR8/SVneo cell line through STAT3 activation.

BACKGROUND: During the first trimester of pregnancy, trophoblastic E-cadherin expression is down-regulated, thereby allowing extravillous trophoblasts (EVTs) to acquire the potential for migration and invasiveness. The aim of the present study was to investigate the role of OSM on the migration and proliferation of EVT cell line HTR8/SVneo with regard to its effects on the expression of E-cadherin and STAT3 activation. METHODS: We investigated the effects of OSM on RNA and protein expression of E-cadherin by real time RT-PCR analyses, western blotting, and indirect immunofluorescence staining in HTR8/SVneo cells, as well as the effects on cell migration and proliferation. The selective signal transducer and activator of transcription (STAT)3 inhibitor, stattic, and STAT3 siRNA were used to investigate STAT3 activation by OSM. RESULTS: OSM significantly reduced RNA and protein expression of E-cadherin. Indirect immunofluorescence staining of HTR8/SVneo cells also revealed the down-regulation of E-cadherin, compared with the controls. OSM-stimulated cell migration was attenuated by anti-gp130 antibodies. OSM-induced STAT3 phosphorylation, and the down-regulation of E-cadherin by OSM treatment was restored by stattic and STAT3 siRNA. In addition, OSM-stimulated migration and proliferation were significantly suppressed by STAT3 inhibition. CONCLUSIONS: This study suggests that OSM stimulates the migration and proliferation of EVTs during the first trimester of pregnancy through the down-regulation of E-cadherin. In addition, this study suggests that the effects of OSM on migration and proliferation are related to STAT3 activation, which is important in trophoblast invasiveness.

Nasolabial dimensions of the facial profile at 20 to 37 weeks' gestation on 2- and 3-dimensional sonography in normal Korean fetuses.

OBJECTIVES: The purpose of this study was to evaluate normal nasolabial dimensions using the images of facial profiles in normal Korean fetuses. METHODS: We conducted a cross-sectional study of 355 normal fetuses at 14 to 39 weeks' gestation. After the exclusion of inadequate images and inadequate numbers of fetuses at 14 to 19 and 37 to 39 weeks' gestation, the sonographic facial profiles from 222 fetuses at 20 to 37 weeks' gestation were evaluated. Five parameters, nose length, nose protrusion, pronasal-subnasal distance, distance between the upper philtrum and mouth, and distance between the tip of the nose and mouth, were measured and are presented according to gestational age. Data were analyzed by intraclass correlation coefficients and regression analysis. RESULTS: There were significant linear correlations between gestational age and nose length (R = 0.390; P < .001), pronasal-subnasal distance (R = 0.415; P < .001), and distance between the upper philtrum and mouth (R = 0.315; P < .001). There were significant quadratic relationships between gestational age and nose protrusion (R(2) = 0.213; P < .001) and distance between the tip of the nose and mouth (R(2) = 0.173; P < .001). CONCLUSIONS: We provide preliminary normative nasolabial dimensions of facial profiles at 20 to 37 weeks' gestation in normal Korean fetuses. These data may be of help not only in the understanding of normal nasolabial growth in utero but also in the diagnosis of abnormal facial dimensions.

Mesenchymal hamartoma of the chest wall: prenatal sonographic manifestations.

Mesenchymal hamartoma of the chest wall is a rare, benign lesion that arises from one or more ribs, almost exclusively found in infants. Some cases that developed in the fetal period have been reported, but accurate diagnosis was usually possible only after birth, except in a few cases in which fetal magnetic resonance imaging or computed tomography were performed. We present a case of a congenital mesenchymal hamartoma of the chest wall. Although the diagnosis was not confirmed until birth, the prenatal sonographic examination showed strongly suggestive findings. We review the published reports on this condition, and suggest the prenatal sonographic features. Prenatal sonography is valuable in the differential diagnosis of chest mass.

Obstructive sleep apnea screening and perinatal outcomes in Korean pregnant women.

PURPOSE: This study was intended to evaluate the attributable risk of obstructive sleep apnea (OSA) by a sleep questionnaire to adverse pregnancy outcomes. METHODS: This was a prospective, cohort study in Korean pregnant women. Berlin questionnaire was employed for symptom-based OSA screening during the third trimester and obstetric outcome data were obtained in 276 deliveries. The relationship between symptom-based OSA and outcomes were explored using SPSS version 18.0 and stratified by obesity (BMI strata <30 and ≥30). Our primary outcome was the compound occurrence of SGA (fetal) or preeclampsia (maternal). Multivariate models were applied in controlling for potential confounders. RESULTS: The overall prevalence of OSA was 32.2 % and it was significantly related with the higher maternal BMI, more body weight at delivery, and weight gain during pregnancy (p = 0.007, p = 0.003, p = 0.005, respectively). There were no significant differences in the primary outcomes according to the positivity of OSA by screening, regardless of the stratification by obesity. The cesarean delivery rate was significantly higher in the OSA positive group (36.0 vs 22.5 %, p = 0.018), but it was not significant in the each strata of obesity. In multivariate analysis, the outcomes of birth weight, preeclampsia, cesarean delivery, and small for gestational age were also not different according to the positivity of OSA. CONCLUSIONS: It seems that the prevalence of OSA by a sleep questionnaire is overestimating OSA in Korean pregnant women. Polysomnography might be needed to diagnose OSA and to evaluate the relationship between OSA and the occurrence of SGA or preeclampsia.

Visible light-curable methacrylated glycol chitosan hydrogel patches for prenatal closure of fetal myelomeningocele.

In this study, we prepared visible light-curable methacrylated glycol chitosan (MGC) hydrogel patches for the prenatal treatment of fetal myelomeningocele (MMC) and investigated their feasibility using a retinoic acid-induced fetal MMC rat model. 4, 5, and 6 w/v% of MGC were selected as candidate precursor solutions, and photo-cured for 20 s, because the resulting hydrogels were found to possess concentration dependent tunable mechanical properties and structural morphologies. Moreover, these materials exhibited no foreign body reactions with good adhesive properties in animal studies. The inflammation scoring assessment in vivo exhibited the absence of foreign body reactions in MGC hydrogel treated lesion. The complete epithelial coverage of MMC was made with using 6 w/v% MGC hydrogel followed by well-organized granulation along with noticeable decrease of abortion rate and wound size that highlight the therapeutic potential for the prenatal treatment of fetal MMC.

Efficient nonadhesive ex vivo expansion of early endothelial progenitor cells derived from CD34+ human cord blood fraction for effective therapeutic vascularization.

Endothelial progenitor cells (EPCs) have been shown to have therapeutic potential in ischemic disease. However, the number of EPCs for cell therapy is limited. In this study, instead of the typical adherent culture method, we investigated a more efficient, clinically applicable nonadhesive expansion method for early EPCs using cord blood-derived cells to overcome rapid cellular senescence. After a suspension culture of isolated CD34(+) cells in serum-free medium containing each cytokine combination was maintained for 9 d, the number of expanded functional EPCs was assessed by an adherent culture assay. Compared to mononuclear cells, the CD34(+) fraction was superior in its expansion of functional EPCs that could differentiate into acLDL/UEA-1(+) cells without significant cellular senescence, whereas the CD34(-) fraction showed no EPC expansion. Among the cytokine combinations tested for the CD34(+) fraction, a combination (SFIb) consisting of stem cell factor (SCF), FMS-like tyrosine kinase 3 ligand, interleukin-3, and basic fibroblast growth factor resulted in a reproducible 64- to 1468-fold EPC expansion from various cord blood origins. Interestingly, the SFIb combination displayed markedly increased EPC expansion (2.43-fold), with a higher percentage of CD34(+) cells (2.17-fold), undifferentiated blasts (2.38-fold) and CXCR4(+) cells (1.68-fold) compared to another cytokine combination (SCF, thrombopoietin, and granulocyte colony-stimulating factor), although the two cytokine combinations had a similar level of total mononucleated cell expansion (∼ 10% difference). Accordingly, the cells expanded in the SFIb combination were more effective in recovery of blood flow and neovascularization in hind-limb ischemia in vivo. Taken together, these results suggest that the nonadhesive serum-free culture conditions of the CD34(+) fraction provide an effective EPC expansion method for cell therapy, and an expansion condition leading to high percentages of CD34(+) cells and blasts is likely important in EPC expansion.

Structure-based virtual screening approach to the discovery of p38 MAP kinase inhibitors.

p38 Mitogen-activated protein kinase (MAPK) has been considered to be a promising target for the development of therapeutics for various immunologic diseases. Herein we report an example for a successful application of the virtual screening with protein-ligand docking to identify the novel inhibitors of p38α MAPK. These inhibitors were screened for having desirable physicochemical properties as a drug candidate and compound 1-3 revealed a moderate inhibitory activity with IC(50) values ranging from 0.7 to 20 µM. Therefore, they deserve a consideration for further development by structure-activity relationship (SAR) studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of p38 MAPK are addressed in detail.

The simplified Edinburgh Postnatal Depression Scale (EPDS) for antenatal depression: is it a valid measure for pre-screening?

The identification of antenatal depression is critical but poorly conducted. The aim of this study was to construct a simplified depression survey scale and to verify its efficacy as a pre-screening for antenatal depression. A total of 494 pregnant women in the third trimester of gestation who had received antenatal care at Seoul St. Mary's Hospital from July 2009 to June 2010 were included. The Edinburgh Postnatal Depression Scale (EPDS) questionnaire was completed by them. The subjects were randomly divided into two groups: 250 of training set and 244 of validation set. We designed a simplified questionnaire comprising two items of EPDS using the training set. We then validated its efficacy with the training set and reaffirmed the results with the validation set. The sum of item 5 (scare or panic) and item 8 (sadness or misery) explained 75.5% of the total score of the EPDS (AUC = 0.947). Using a score of 3 as a cut-off value of the simplified scale, sensitivity was 92.4% and specificity was 86.3%. The positive and negative predictive values were 56.2% and 98.4%, retrospectively. This study suggests that the simplified EPDS can be an efficient instrument to rule out depression during pregnancy.