Papers - Kasuga, Yoshifumi

Newer Insights Into Fetal Growth and Body Composition

Ikenoue S., Kasuga Y., Endo T., Tanaka M., Ochiai D.

Frontiers in Endocrinology (Frontiers in Endocrinology)  12   708767 2021.07

Accepted,  ISSN  1664-2392

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Based on epidemiological and experimental evidence, the origins of childhood obesity and early onset metabolic syndrome can be extended back to developmental processes during intrauterine life. It is necessary to actively investigate antecedent conditions that affect fetal growth by developing reliable measures to identify variations in fetal fat deposition and body composition. Recently, the resolution of ultrasonography has remarkably improved, which enables better tissue characterization and quantification of fetal fat accumulation. In addition, fetal fractional limb volume has been introduced as a novel measure to quantify fetal soft tissue volume, including fat mass and lean mass. Detecting extreme variations in fetal fat deposition may provide further insights into the origins of altered fetal body composition in pathophysiological conditions (i.e., fetal growth restriction or fetal macrosomia), which are predisposed to the metabolic syndrome in later life. Further studies are warranted to determine the maternal or placental factors that affect fetal fat deposition and body composition. Elucidating these factors may help develop clinical interventions for altered fetal growth and body composition, which could potentially lead to primary prevention of the future risk of metabolic dysfunction.

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Epigenetic Changes in Neonates Born to Mothers With Gestational Diabetes Mellitus May Be Associated With Neonatal Hypoglycaemia

Kasuga Y., Kawai T., Miyakoshi K., Saisho Y., Tamagawa M., Hasegawa K., Ikenoue S., Ochiai D., Hida M., Tanaka M., Hata K.

Frontiers in Endocrinology (Frontiers in Endocrinology)  12   690648 2021.06

Accepted,  ISSN  1664-2392

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The detection of epigenetic changes associated with neonatal hypoglycaemia may reveal the pathophysiology and predict the onset of future diseases in offspring. We hypothesized that neonatal hypoglycaemia reflects the in utero environment associated with maternal gestational diabetes mellitus. The aim of this study was to identify epigenetic changes associated with neonatal hypoglycaemia. The association between DNA methylation using Infinium HumanMethylation EPIC BeadChip and neonatal plasma glucose (PG) level at 1 h after birth in 128 offspring born at term to mothers with well-controlled gestational diabetes mellitus was investigated by robust linear regression analysis. Cord blood DNA methylation at 12 CpG sites was significantly associated with PG at 1 h after birth after adding infant sex, delivery method, gestational day, and blood cell compositions as covariates to the regression model. DNA methylation at two CpG sites near an alternative transcription start site of ZNF696 was significantly associated with the PG level at 1 h following birth (false discovery rate-adjusted P < 0.05). Methylation levels at these sites increased as neonatal PG levels at 1 h after birth decreased. In conclusion, gestational diabetes mellitus is associated with DNA methylation changes at the alternative transcription start site of ZNF696 in cord blood cells. This is the first report of DNA methylation changes associated with neonatal PG at 1 h after birth.

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Predictors of later insulin therapy for gestational diabetes diagnosed in early pregnancy.

Tamagawa M, Kasuga Y, Saisho Y, Tanaka Y, Hasegawa K, Oishi M, Endo T, Sato Y, Ikenoue S, Tanaka M, Ochiai D

Endocrine journal (Endocrine Journal)  68 ( 11 ) 1321 - 1328 2021.06

Accepted,  ISSN  0918-8959

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Interventions for gestational diabetes mellitus (GDM), diagnosed in early pregnancy, have been a topic of controversy. This study aimed to elucidate factors that predict patients with GDM diagnosed before 24 gestational weeks (early GDM: E-GDM) who require insulin therapy later during pregnancy. Furthermore, we identified patients whose impaired glucose tolerance should be strictly controlled from early gestation onward. Women diagnosed with GDM were categorized based on the gestational age at diagnosis into E-GDM (n = 388) or late GDM (L-GDM, diagnosed after 24 weeks, n = 340) groups. Clinical features were compared between the groups, and the predictors for insulin therapy was evaluated in the E-GDM group. There were no significant between-group differences in terms of perinatal outcomes (e.g., gestational weeks at delivery, fetal growth, hypertensive disorder of pregnancy), with the exception of the Apgar score at 5 min. Moreover, there was no significant difference in the frequency of insulin therapy during pregnancy between the two groups. Using multiple logistic regression analysis, pre-pregnancy body mass index (BMI) ≥25 kg/m2, a family history of diabetes, and higher fasting plasma glucose (FPG), 1 h-plasma glucose (PG), and 2 h-PG values increased insulin therapy risk during pregnancy in the E-GDM group. Furthermore, since E-GDM patients with abnormal levels of FPG, as well as 1 h-PG or 2 h-PG, and those with pre-pregnancy BMI ≥25 kg/m2 and a family history of diabetes had a higher risk of later insulin therapy during pregnancy, they may require more careful follow-up in the perinatal period.

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What are the causes for low birthweight in Japan? A single hospital-based study

Kasuga Y., Ikenoue S., Tamagawa M., Oishi M., Endo T., Sato Y., Iida M., Sato Y., Tanaka M., Ochiai D.

PLoS ONE (PLoS ONE)  16 ( 6 June ) e0253719 2021.06

Accepted

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Low-birthweight (LBW; <2,500 g) babies are at a higher risk of poor educational achievement, disability, and metabolic diseases than normal-birthweight babies in the future. However, reliable data on factors that contribute to LBW have not been considered previously. Therefore, we aimed to examine the distribution of the causes for LBW. A retrospective review of cases involving 4,224 babies whose mothers underwent perinatal care at Keio University Hospital between 2013 and 2019 was conducted. The LBW incidence was 24% (1,028 babies). Of the 1,028 LBW babies, 231 babies were from multiple pregnancies. Of the 797 singleton LBW babies, 518 (65%) were born preterm. Obstetric complications in women with preterm LBW babies included premature rupture of membrane or labor onset (31%), hypertensive disorders of pregnancy (HDP, 64%), fetal growth restriction (24%), non-reassuring fetal status (14%), and placental previa/vasa previa (8%). Of the 279 term LBW babies, 109 (39%) were small for gestational age. Multiple logistic regression analyses revealed the following factors as LBW risk factors in term neonates: low pre-pregnancy maternal weight, inadequate gestational weight gain, birth at 37 gestational weeks, HDP, anemia during pregnancy, female sex, and neonatal congenital anomalies. HDP was an LBW risk factor not only in preterm births but also in term births. Our results suggest that both modifiable and non-modifiable factors are causes for LBW. It may be appropriate to consider a heterogeneous rather than a simple classification of LBW and to evaluate future health risks based on contributing factors.

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Management of pregnancy after radical trachelectomy.

Kasuga Y, Ikenoue S, Tanaka M, Ochiai D

Gynecologic oncology (Gynecologic Oncology)  162 ( 1 ) 220 - 225 2021.04

Accepted,  ISSN  0090-8258

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Radical trachelectomy (RT) is a surgery for early-stage cervical cancer treatment that preserves the childbearing ability, and its use has become increasingly common worldwide. Thus, the rate of conception in women who have undergone RT is increasing. However, pregnancy after RT is associated with a higher risk of several obstetric complications such as preterm delivery, preterm premature membrane rupture, and abnormal bleeding from varices at the site of uterovaginal anastomosis. Furthermore, since RT have a residual prophylactic cerclage, it is difficult to manage first- and second-trimester miscarriages. There is little previous data on the management of pregnancy after RT. In this review article, we summarize various management methods and experiences to provide a guide to clinicians for perinatal management after RT.

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帝王切開術後の腹腔内出血に対し、腹部コンパートメント症候群に準じて治療介入した1例

大石 真希, 落合 大吾, 春日 義史, 田中 雄也, 玉川 真澄, 遠藤 豊英, 佐藤 佑, 池ノ上 学, 田中 守, 青木 大輔

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会)  70 ( 2 ) 231 - 236 2021.04

Accepted,  ISSN  2186-0599

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産科領域における腹部コンパートメント症候群(abdominal compartment syndrome:ACS)の報告は稀である。今回我々は、帝王切開術後に腹腔内出血を認め、ACSに準じて加療した症例を経験した。症例は43歳、妊娠39週0日に分娩中に児の持続徐脈を認め、超緊急帝王切開術を施行し常位胎盤早期剥離と診断した。帰室1時間後、出血性ショック状態のため産科危機的出血を宣言し子宮動脈塞栓術を施行した。術後1日目、著明な腹部膨隆を認め、ACSを疑い腹部造影CT検査を行ったが臓器血流障害は認めなかった。また、膀胱内圧は14mmHgと上昇しており、約4Lの血性腹水を経腹的にドレナージしたところ呼吸状態が劇的に改善した。そして、その後の経過は順調で術後7日目に退院した。ACS疑いの症例では、腹腔内圧の推定には膀胱内圧が有用であり、早期の治療介入が病態改善に寄与する可能性が示唆された。(著者抄録)

Cell sheets using human amniotic fluid stem cells reduce tissue fibrosis in murine full-thickness skin wounds

Ochiai D., Abe Y., Fukutake M., Sato Y., Ikenoue S., Kasuga Y., Masuda H., Tanaka M.

Tissue and Cell (Tissue and Cell)  68   101472 2021.02

Accepted,  ISSN  00408166

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The use of mesenchymal stem cell sheets is a promising strategy for skin regeneration. The injection of dissociated human amniotic fluid stem cells (hAFSCs) was recently found to accelerate cutaneous wound healing with reduced fibrotic scarring, similar to fetal wound healing. However, the use of hAFSCs in applications of cell sheet technology remains limited. The aim of this study was to determine the in vivo efficacy of in vitro-cultured hAFSC sheets in wound healing. The cell sheets were characterized by immunohistochemistry and RT-qPCR and grafted onto full-thickness wounds in BALB/c mice. The wound size was measured, and re-epithelialization, granulation tissue area, and collagen content of the regenerated wound were analyzed histologically. Although the hAFSC sheet contained abundant extracellular matrix molecules and expressed high levels of anti-fibrotic mediators, its grafting did not affect wound closure or the size of the granulation tissue area. In contrast, the organization of type I collagen bundles in the regenerated wound was markedly reduced, while the levels of type III collagen were increased after implantation of the hAFSC sheet. These results suggest that hAFSC sheets can exert anti-fibrotic properties without delaying wound closure.

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Defining the Normal Growth Curve of Fetal Fractional Limb Volume in a Japanese Population.

Ikenoue S, Akiba Y, Endo T, Kasuga Y, Yakubo K, Ishii R, Tanaka M, Ochiai D

Journal of clinical medicine (Journal of Clinical Medicine)  10 ( 3 ) 1 - 9 2021.01

Accepted,  ISSN  2077-0383

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Fetal fractional limb volume is a useful measure for predicting birth weight and newborn adiposity; however, a normal growth curve has been reported solely in the United States. As the birth weight of neonates in Japan is significantly lower than that in the US, fetal fractional limb volume is likely to be smaller in the Japanese population. This study aimed to define the normal growth curve of fractional arm volume (AVol) and thigh volume (TVol) in the Japanese population. Ultrasound scans of 453 AVol and TVol pairs were obtained; each AVol and TVol percentile at each gestational age was calculated. The measured AVol and TVol at each gestational week were also converted to z-scores based on a previous report. The growth curves increased linearly until the second trimester and exponentially in the third trimester. Linear regression showed a significant negative correlation between gestational age and AVol and TVol z-scores. The growth pattern of fetal fractional limb volume in the Japanese population is consistent with, but smaller than, that reported in the US; this difference becomes greater as the gestational age progresses.

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Amniotic fluid stem cells as a novel strategy for the treatment of fetal and neonatal neurological diseases

Abe Y., Ochiai D., Sato Y., Otani T., Fukutake M., Ikenoue S., Kasuga Y., Tanaka M.

Placenta (Placenta)  104   247 - 252 2021.01

Accepted,  ISSN  01434004

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Even in the context of modern medicine, infants with fetal and neonatal neurological diseases such as cerebral palsy and myelomeningocele suffer serious long-lasting impairment due to the irreversible neuronal damage. The promotion of neurologically intact survival in patients with perinatal intractable neurological diseases requires the development of novel strategies. One promising strategy involves the use of human amniotic fluid stem cells (hAFSCs), which have attracted much attention in recent years and are known to exert anti-inflammatory and neuroprotective effects. In recent years, the therapeutic effects of hAFSCs on fetal-neonatal neurological diseases have become evident as per intense research efforts by our group and others. Specifically, hAFSCs administered into the nasal cavity migrated to the brain and controlled local inflammation in a rodent model of neonatal hypoxic-ischemic encephalopathy. In contrast, hAFSCs administered intraperitoneally did not migrate to the brain; they rather formed spheroids in the abdominal cavity, resulting in the suppression of systemic inflammation (including in the brain) via the secretion of anti-inflammatory cytokines in concert with peritoneal macrophages in a rodent model of periventricular leukomalacia. Moreover, studies in a rat model of myelomeningocele suggested that hAFSCs administered in utero secreted hepatocyte growth factor and protected the exposed spinal cord during pregnancy. Importantly, autologous hAFSCs, whose use for fetal-neonatal treatment does not raise ethical issues, can be collected during pregnancy and prepared in sufficient numbers for therapeutic use. This article outlines the results of preclinical research on fetal stem cell therapy, mainly involving hAFSCs, in the context of perinatal neurological diseases.

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A safe delivery system to prevent COVID-19 transmission without negative-pressure isolation delivery rooms: Experience from a hospital with nosocomial outbreak

Kasuga Y., Ochiai D., Tamagawa M., Oishi M., Endo T., Sato Y., Iida M., Ikenoue S., Tanaka M.

Taiwanese Journal of Obstetrics and Gynecology (Taiwanese Journal of Obstetrics and Gynecology)  60 ( 1 ) 183 - 184 2021.01

Accepted,  ISSN  10284559

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A case of abdominal compartment syndrome caused by amniotic fluid embolism treated with ABTHERA™ therapy: World's first report in the obstetric field

Hirata M., Hasegawa K., Kasuga Y., Haiden A., Ikenoue S., Yamamoto R., Tanaka M., Sasaki J., Ochiai D.

Taiwanese Journal of Obstetrics and Gynecology (Taiwanese Journal of Obstetrics and Gynecology)  60 ( 3 ) 579 - 580 2021

Accepted,  ISSN  10284559

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Expectant management for early pregnancy miscarriage after radical trachelectomy: A single hospital-based study

Kasuga Y., Ikenoue S., Tanaka Y., Tamagawa M., Hasegawa K., Oishi M., Endo T., Sato Y., Tanaka M., Ochiai D.

Acta Obstetricia et Gynecologica Scandinavica (Acta Obstetricia et Gynecologica Scandinavica)  100 ( 7 ) 1322 - 1325 2021

Accepted,  ISSN  00016349

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Introduction: Women who have undergone radical trachelectomy as a fertility-sparing treatment for early-stage cervical cancer may be at higher risk for retained tissues after early-term miscarriage due to cervical cerclage or cervical necrosis. Dilatation and curettage or aspiration may present additional risks in these women. The aim of this study was to assess the efficacy of expectant management for early pregnancy miscarriage after radical trachelectomy. Material and methods: Keio University Hospital records were reviewed for women who conceived after abdominal radical trachelectomy and received perinatal care between 1 April 2012 and 31 March 2020. A total of 62 women (76 pregnancies) were identified, and 13 of these women experienced miscarriage before 12 gestational weeks. The management and outcome of these cases were reviewed in detail. Results: The median maternal age at miscarriage was 39 years (range 31–42 years) and the median duration from abdominal radical trachelectomy to conception was 2.60 years (range 0.49–7.30 years). Cervical necrosis before conception occurred in one case (8%). One patient requested treatment with aspiration and the remaining 12 cases were managed with observation for a median of 23 days (range 7–50 days). There were no cases of endometritis or cases requiring dilatation and curettage for residue tissue. Further, no cases developed laceration of the residual cervix and no loss of cerclage sutures after discharge was noted. Conclusions: Expectant management seems to be safe and appropriate for first trimester miscarriage after abdominal radical trachelectomy.

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Clinical utility of 1-month postpartum random plasma glucose and glycated hemoglobin combined with pre-pregnancy body mass index for detecting postpartum glucose intolerance in Japanese women with gestational diabetes

Sugiyama K., Saisho Y., Kasuga Y., Ochiai D., Itoh H.

Journal of Diabetes Investigation (Journal of Diabetes Investigation)  12 ( 12 ) 2242 - 2246 2021

Accepted,  ISSN  20401116

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During the coronavirus disease 2019 pandemic, the Japanese Society of Diabetes and Pregnancy proposed the use of random plasma glucose and glycated hemoglobin measured 1 month after delivery combined with pre-pregnancy body mass index to detect postpartum glucose intolerance instead of carrying out the oral glucose tolerance test in women with gestational diabetes. We retrospectively evaluated the clinical utility of this strategy to detect postpartum glucose intolerance evaluated by the oral glucose tolerance test after delivery. A total of 275 Japanese women with gestational diabetes were included in the present study. The specificity of 1-month postpartum random plasma glucose and glycated hemoglobin combined with pre-pregnancy body mass index to predict postpartum glucose intolerance was 98.0%, with a negative predictive value of 72.6%. However, sensitivity was 6.4%, with a positive predictive value of 55.6%. In conclusion, this Japanese Society of Diabetes and Pregnancy strategy showed high specificity, but low sensitivity, for detecting glucose intolerance postpartum.

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Prophylactic therapy with human amniotic fluid stem cells improves long-term cognitive impairment in rat neonatal sepsis survivors

Abe Y., Ochiai D., Sato Y., Kanzaki S., Ikenoue S., Kasuga Y., Tanaka M.

International Journal of Molecular Sciences (International Journal of Molecular Sciences)  21 ( 24 ) 1 - 12 2020.12

Accepted,  ISSN  16616596

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A systemic inflammatory response induces multiple organ dysfunction and results in poor long-term neurological outcomes in neonatal sepsis. However, there is no effective therapy for treating or preventing neonatal sepsis besides antibiotics and supportive care. Therefore, a novel strategy to improve neonatal sepsis-related morbidity and mortality is desirable. Recently, we reported that prophylactic therapy with human amniotic stem cells (hAFSCs) improved survival in a rat model of lipopolysaccharide (LPS)-induced neonatal sepsis through immunomodulation. Besides improving the mortality, increasing survival without major morbidities is an important goal of neonatal intensive care for neonatal sepsis. This study investigated long-term neurological outcomes in neonatal sepsis survivors treated with hAFSCs using the LPS-induced neonatal sepsis model in rats. We found that prophylactic therapy with hAFSCs improved spatial awareness and memory-based behavior in neonatal sepsis survivors at adolescence in rats. The treatment suppressed acute reactive gliosis and subsequently reduced astrogliosis in the hippocampal region over a long period of assessment. To the best of our knowledge, this is the first report that proves the concept that hAFSC treatment improves cognitive impairment in neonatal sepsis survivors. We demonstrate the efficacy of hAFSC therapy in improving the mortality and morbidity associated with neonatal sepsis.

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特定妊婦への選定状況からみた当院における精神疾患合併妊娠の実態

桑名 温子, 清河 駿樹, 大橋 千恵, 今村 裕子, 石垣 順子, 鈴木 毅, 金 善惠, 樋口 隆幸, 林 保良, 染谷 健一, 中田 さくら, 春日 義史

関東連合産科婦人科学会誌 ((一社)関東連合産科婦人科学会)  57 ( 4 ) 431 - 436 2020.11

Accepted,  ISSN  2186-0610

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分娩後の養育について妊娠中からの公的支援が必要と考えられる妊婦を特定妊婦に選定し,多職種が連携して支援している.精神疾患合併妊娠は特定妊婦選定の理由の1つとなりうるが,家庭環境などを考慮し非選定例も多い.本研究の目的は,精神疾患合併妊娠を特定妊婦選定の有無で分類し検討することでその背景を明らかにすることとした.対象は2018年1月から2019年8月に当院で対応した精神疾患の既往または合併のある妊婦118例(特定妊婦28例,非特定妊婦90例)であり,当院倫理委員会承認のもと母体背景,精神疾患診断名と治療状況,周産期予後について検討した.特定妊婦群では若年妊娠(p<0.05),未婚,生活保護受給者,妊娠中の内服継続,通院継続,治療の自己中断歴(各々p<0.01)が有意に多かった.特定妊婦群ではうつ病以外にパーソナリティー障害や精神発達遅滞が多く,覚醒剤使用後遺症が3例あった.周産期予後について有意差はなかった.7例が児童相談所に保護となり,いずれも特定妊婦群であった.周産期予後に差はないものの,児童相談所保護が多いことから,妊娠中から地域との連携をスムーズにするという点で特定妊婦選定の意義が再認識された.医療機関においては一般診療以外の労力が大きいことから,選定対象と具体的な対応については今後も検討が必要であると考えられた.(著者抄録)

Preterm delivery and hypertensive disorder of pregnancy were reduced during the COVID-19 pandemic: A single hospital-based study.

Kasuga Y, Tanaka M, Ochiai D

The journal of obstetrics and gynaecology research 46 ( 12 ) 2703 - 4 2020.10

ISSN  1341-8076

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Sonographic findings of cervical laceration caused by vaginal delivery in pregnancy after radical trachelectomy.

Kasuga Y, Miyakoshi K, Endo T, Takeda T, Nakamura M, Ochiai D, Tanaka M

Journal of medical ultrasonics (2001) 47 ( 4 ) 655 - 657 2020.10

ISSN  1346-4523

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Prophylactic therapy with human amniotic fluid stem cells improved survival in a rat model of lipopolysaccharide-induced neonatal sepsis through immunomodulation via aggregates with peritoneal macrophages.

Sato Y, Ochiai D, Abe Y, Masuda H, Fukutake M, Ikenoue S, Kasuga Y, Shimoda M, Kanai Y, Tanaka M

Stem cell research & therapy (Stem Cell Research and Therapy)  11 ( 1 ) 300 2020.07

Accepted

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Background: Despite recent advances in neonatal care, sepsis remains a leading cause of mortality in neonates. Mesenchymal stem cells derived from various tissues, such as bone marrow, umbilical cord, and adipose tissue, have beneficial effects on adult sepsis. Although human amniotic fluid stem cells (hAFSCs) have mesenchymal stem cell properties, the efficacy of hAFSCs on neonatal sepsis is yet to be elucidated. This study aimed to investigate the therapeutic potential of hAFSCs on neonatal sepsis using a rat model of lipopolysaccharide (LPS)-induced sepsis. Methods: hAFSCs were isolated as CD117-positive cells from human amniotic fluid. Three-day-old rat pups were intraperitoneally treated with LPS to mimic neonatal sepsis. hAFSCs were administered either 3 h before or at 0, 3, or 24 h after LPS exposure. Serum inflammatory cytokine levels, gene expression profiles from spleens, and multiple organ damage were analyzed. hAFSC localization was determined in vivo. In vitro LPS stimulation tests were performed using neonatal rat peritoneal macrophages co-cultured with hAFSCs in a cell-cell contact-dependent/independent manner. Immunoregulation in the spleen was determined using a DNA microarray analysis. Results: Prophylactic therapy with hAFSCs improved survival in the LPS-treated rats while the hAFSCs transplantation after LPS exposure did not elicit a therapeutic response. Therefore, hAFSC pretreatment was used for all subsequent studies. Inflammatory cytokine levels were elevated after LPS injection, which was attenuated by hAFSC pretreatment. Subsequently, inflammation-induced damages in the brain, lungs, and liver were ameliorated. hAFSCs aggregated with peritoneal macrophages and/or transiently accumulated in the liver, mesentery, and peritoneum. Paracrine factors released by hAFSCs induced M1-M2 macrophage polarization in a cell-cell contact-independent manner. Direct contact between hAFSCs and peritoneal macrophages further enhanced the polarization. Microarray analysis of the spleen showed that hAFSC pretreatment reduced the expression of genes involved in apoptosis and inflammation and subsequently suppressed toll-like receptor 4 signaling pathways. Conclusions: Prophylactic therapy with hAFSCs improved survival in a rat model of LPS-induced neonatal sepsis. These effects might be mediated by a phenotypic switch from M1 to M2 in peritoneal macrophages, triggered by hAFSCs in a cell-cell contact-dependent/independent manner and the subsequent immunomodulation of the spleen.

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Universal screening for SARS-CoV-2 in asymptomatic obstetric patients in Tokyo, Japan.

Ochiai D, Kasuga Y, Iida M, Ikenoue S, Tanaka M

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics (International Journal of Gynecology and Obstetrics)  150 ( 2 ) 268 - 269 2020.06

Accepted,  ISSN  0020-7292

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A new diagnostic strategy for gestational diabetes during the COVID-19 pandemic for the Japanese population.

Kasuga Y, Saisho Y, Ikenoue S, Ochiai D, Tanaka M

Diabetes/metabolism research and reviews 36 ( 8 ) e3351 2020.05

Accepted,  ISSN  1520-7552

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