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1.
Radiol Case Rep ; 19(4): 1463-1467, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38304349

RESUMO

Here, we report a case of a congenital peribronchial myofibroblastic tumor (CPMT). A 34-year-old primigravida was referred to our hospital at 31 gestation weeks because of suspected congenital pulmonary airway malformation (CPAM). Fetal ultrasonography showed a mass measuring 4.6 × 4.0 × 3.9 cm with mixed high and low echogenicity in the left lung, which was associated with microvascular blood flow in the tumor. Fetal magnetic resonance imaging (MRI) revealed a low-intensity left lobe lung lesion on a T2-weighted image. These findings suggested that the mass was a CPAM with atypical hypointense findings on MRI T2-weighted images or a rare primary pulmonary tumor, such as a CPMT. Unfortunately, the fetus died in utero at 34 gestation weeks due to cardiovascular failure, which could have resulted from direct encasement of the great vessels or cardiac compression due to rapid tumor growth. The autopsy findings confirmed the diagnosis of CPMT. Primary pulmonary tumors, such as CPMT, are extremely rare lung diseases that develop in utero. These tumors often rapidly grow during pregnancy, resulting in intrauterine fetal death. However, if the patient survives surgical mass resection, the prognosis is good. Given the adverse outcomes observed in our case, careful fetal monitoring is required in case of suspected CPMT during the third trimester of pregnancy. Moreover, in case the well-being of the fetus cannot be assured, immediate delivery should be considered, even in the preterm period, followed by surgery.

2.
Histol Histopathol ; 38(9): 965-974, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36971371

RESUMO

This paper describes the current status of studies and clinical trials on the use of mesenchymal stem cells (MSCs) and amniotic fluid stem cells (AFSCs) for complications of preterm birth (PTB), an urgent issue in the perinatal field. PTB is a serious challenge in clinical medicine that is increasing globally, and effective control of its complications is necessary for newborns' subsequent long life. Classical treatments are inadequate, and many patients have PTB complications. A growing body of evidence provided by translational medicine and others indicates that MSCs, and among them, the readily available AFSCs, may be useful in treating PTB complications. AFSCs are the only MSCs available prenatally and are known to be highly anti-inflammatory and tissue-protective and do not form tumors when transplanted. Furthermore, because they are derived from the amniotic fluid, a medical waste product, no ethical issues are involved. AFSCs are an ideal cell resource for MSC therapy in neonates. This paper targets the brain, lungs, and intestines, which are the vital organs most likely to be damaged by PTB complications. The evidence to date and future prospects with MSCs and AFSCs for these organs are described.


Assuntos
Células-Tronco Mesenquimais , Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , Líquido Amniótico , Transplante de Células-Tronco/efeitos adversos , Diferenciação Celular
3.
Case Rep Womens Health ; 37: e00479, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36683783

RESUMO

Dermatomyositis (DM) is one of the most common autoimmune rheumatic diseases affecting women of childbearing age. Pregnancy may lead to exacerbation of DM, especially of DM with anti-melanoma differentiation-associated gene (MDA) 5 antibody positivity, leading to a poor obstetric outcome. Here, we report consecutive pregnancies complicated by DM with anti-MDA-5 antibodies. A 32-year-old pregnant woman, gravida 3 para 1, presented with fetal growth restriction. Emergency cesarean section was performed because of non-reassuring fetal status at 28 weeks of gestation. Two days postpartum, the patient's hand eczema had worsened and she was diagnosed with DM with MDA-5 antibody positivity. Immunosuppressive therapy using corticosteroids combined with tacrolimus was immediately started, suppressing the DM symptoms. Eighteen months later, she became pregnant again but was then negative for anti-MDA-5 antibodies while continuing immunosuppressive therapy. During pregnancy, the titer of the antibody gradually increased, peaked in the second trimester and declined to near normal range through the third trimester. A male infant weighing 2418 g was delivered at 38 weeks of gestation. Our case demonstrates that controlling of DM activity using immunosuppressive treatment before and during pregnancy may be beneficial to obstetric outcomes.

4.
Int J Clin Oncol ; 28(4): 587-591, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36662363

RESUMO

BACKGROUND: To investigate perinatal outcomes in pregnancy after high-dose medroxyprogesterone acetate (MPA) therapy for early stage endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) and to determine whether pregnancy after MPA therapy is at a higher risk of placenta accreta. METHODS: Data of 51 pregnancies in 46 women who received MPA therapy for EC or AEH and delivered after 22 weeks of gestation at Keio University Hospital were reviewed. A retrospective matched case-control study was performed to determine the risk of placenta accreta in pregnancy after MPA therapy compared with singleton pregnancies without any history of maternal malignancy treatments. RESULTS: The incidence of placenta accreta was higher in the MPA group than in the control group (15.7 vs. 0%, p = 0.0058). However, no differences in other perinatal outcomes were observed between groups. While gestational weeks at delivery in the MPA group were later than those in the control group (p = 0.0058), no difference in the incidence of preterm delivery was recorded between groups. In the MPA therapy group, the number of patients who underwent ≥ 6 dilation and curettage (D&C) was higher in the placenta accreta group than in the non-placenta accreta group (50.0 vs. 14.0%, p = 0.018). Patients with ≥ 6 D&Cs demonstrated a 6.0-fold increased risk of placenta accreta (p = 0.043, 95% CI 1.05-34.1) than those receiving ≤ 3 D&Cs. CONCLUSION: Pregnancy after MPA therapy is associated with a high risk of placenta accreta. In cases in which the frequency of D&C is high, placenta accreta should be considered.


Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Hospitais , Acetato de Medroxiprogesterona , Estadiamento de Neoplasias , Placenta Acreta , Feminino , Humanos , Gravidez , Dilatação e Curetagem , Hiperplasia Endometrial/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Acetato de Medroxiprogesterona/efeitos adversos , Acetato de Medroxiprogesterona/uso terapêutico , Placenta Acreta/induzido quimicamente , Placenta Acreta/etiologia , Nascimento Prematuro , Estudos Retrospectivos , Obstetrícia , Adulto , Pessoa de Meia-Idade
5.
J Epidemiol ; 33(9): 450-455, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35370228

RESUMO

BACKGROUND: Progress in reducing the global low birthweight (LBW) has been insufficient. Although the focus has been on preventing preterm birth, evidence regarding LBW in term births is limited. Despite its low preterm birth prevalence, Japan has a higher LBW proportion than other developed countries. This study aimed to examine the prevalence of LBW in term singleton births and its associated factors using a national database. METHODS: We retrospectively analyzed the data of neonates registered in the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System who were born 2013-2017. Exclusion criteria included stillbirths, delivery after 42 gestational weeks, and missing data. Logistic regression analyses were performed to investigate the maternal and perinatal factors associated with LBW in term singletons using the data of 715,414 singleton neonates. RESULTS: The overall prevalence of LBW was 18.3%, and 35.7% of LBWs originated from singleton term pregnancies. Multiple logistic regression analyses indicated that both modifiable and non-modifiable factors were independently associated with LBW in term neonates. The modifiable maternal factors included pre-pregnancy underweight, inadequate gestational weight gain, and smoking during pregnancy, while the non-modifiable factors included younger maternal age, nulliparity, hypertensive disorders of pregnancy, cesarean section delivery, female offspring, and congenital anomalies. CONCLUSION: Using the Japanese pregnancy birth registry data, more than one-third of LBWs were found to originate from singleton term pregnancies. Both modifiable and non-modifiable factors were independently associated with LBW in term neonates. Prevention strategies on modifiable risk factor control will be effective in reducing LBW worldwide.


Assuntos
Nascimento Prematuro , Recém-Nascido , Feminino , Gravidez , Humanos , Peso ao Nascer , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Japão/epidemiologia , Cesárea/efeitos adversos , Fatores de Risco , Sistema de Registros
6.
Mol Cell Biochem ; 478(2): 363-374, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35810415

RESUMO

Ascending inflammation from the vagina is a major cause of preterm birth. Currently, this condition-especially when uncontrolled-has no effective treatment. Human amniotic fluid stem cells (hAFSCs) are mesenchymal stem cells known to exert potent anti-inflammatory effects in animal models of perinatal diseases, such as periventricular leukomalacia, myelomeningocele, and neonatal sepsis. However, hAFSC therapy for inflammation-induced preterm birth has not been tested. In order to determine the therapeutic effect of hAFSC transplantation, we employed a preterm mouse model of ascending infection; this model was constructed by administering lipopolysaccharide to pregnant mice. We investigated the preterm birth rate and evaluated the inflammation of tissues, which is related to progressive infections, such as those involving the cervix, placenta, and lavage cells, using real-time qPCR. Further, we tracked the fluorescence of fluorescently labeled hAFSCs using an in vivo imaging system, and hAFSC aggregation was evaluated using immunohistochemistry analysis. We also investigated the presence of multiple types of peritoneal macrophages via flow cytometry analysis. Finally, we performed sphere culturing and co-culturing to determine the therapeutic effects of hAFSCs, such as their anti-inflammatory effects and their potential to alter macrophage polarization. We found that hAFSC administration to the peritoneal cavity significantly reduced inflammation-induced preterm birth in the mouse model. The treatment also significantly suppressed inflammation of the placenta and cervix. Transplanted hAFSCs may have aggregated with peritoneal macrophages, switching them from an inflammatory to an anti-inflammatory type. This property has been reported in vivo previously, but here, we examined the effect in vitro. Our findings support the hypothesis that hAFSCs suppress inflammation and reduce preterm birth by switching macrophage polarity. This study is the first to demonstrate that hAFSCs are effective in the treatment and prevention of inflammation-induced preterm birth.


Assuntos
Células-Tronco Mesenquimais , Nascimento Prematuro , Gravidez , Feminino , Humanos , Camundongos , Recém-Nascido , Animais , Líquido Amniótico , Nascimento Prematuro/prevenção & controle , Células-Tronco , Inflamação/induzido quimicamente
7.
J Matern Fetal Neonatal Med ; 35(25): 9837-9842, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35341455

RESUMO

OBJECTIVE: Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery. METHODS: We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks). RESULTS: Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity (p = .014) was higher and a history of preterm delivery (p = .0010) was more common in the preterm delivery group than in the term delivery group. Furthermore, the proportion of women diagnosed with adenocarcinoma in situ (AIS) and cervical cancer in the preterm delivery group was higher than that in the term delivery group (p = .0099 and .0004, respectively). In multiple regression models in nulliparous women, cervical cancer or AIS (Odds ratio [OR]: 4.16, 95% CI: 1.26-13.68, p = .019) and a short cervix in the second trimester (OR: 13.41, 95% CI: 3.88-46.42, p < .0001) increased the risk of preterm delivery. Furthermore, a history of preterm delivery (OR: 7.35, 95% CI: 1.55-34.86, p = .012), cervical cancer or AIS (OR: 5.07, 95% CI: 1.24-20.73, p = .024), and a short cervix in the second trimester (OR: 4.29, 95% CI: 1.11-16.62, p = .035) increased the risk of preterm delivery in the multiple regression models in primiparous women. CONCLUSION: Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGESPrior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization.The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.


Assuntos
Adenocarcinoma in Situ , Nascimento Prematuro , Neoplasias do Colo do Útero , Recém-Nascido , Feminino , Humanos , Gravidez , Conização/efeitos adversos , Colo do Útero/patologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/etiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/diagnóstico , Adenocarcinoma in Situ/etiologia , Adenocarcinoma in Situ/patologia , Adenocarcinoma in Situ/cirurgia , Estudos Retrospectivos , Fatores de Risco
8.
Acta Obstet Gynecol Scand ; 100(7): 1322-1325, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33797065

RESUMO

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.


Assuntos
Aborto Espontâneo/etiologia , Complicações Neoplásicas na Gravidez/cirurgia , Resultado da Gravidez/epidemiologia , Traquelectomia/efeitos adversos , Neoplasias do Colo do Útero/cirurgia , Conduta Expectante , Adulto , Feminino , Seguimentos , Humanos , Gravidez , Resultado do Tratamento
9.
Gynecol Oncol ; 162(1): 220-225, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33902946

RESUMO

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.


Assuntos
Gravidez , Traquelectomia , Feminino , Humanos , Resultado da Gravidez
10.
Placenta ; 104: 247-252, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33461069

RESUMO

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.


Assuntos
Líquido Amniótico/citologia , Paralisia Cerebral/terapia , Hipóxia-Isquemia Encefálica/terapia , Leucomalácia Periventricular/terapia , Meningomielocele/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Animais , Feminino , Humanos , Gravidez , Ratos
11.
Int J Mol Sci ; 21(24)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339379

RESUMO

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.


Assuntos
Disfunção Cognitiva/prevenção & controle , Gliose/prevenção & controle , Transplante de Células-Tronco Mesenquimais/métodos , Sepse Neonatal/complicações , Líquido Amniótico/citologia , Animais , Células Cultivadas , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Gliose/etiologia , Gliose/terapia , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Sprague-Dawley
12.
Stem Cell Res Ther ; 11(1): 300, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32690106

RESUMO

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.


Assuntos
Sepse Neonatal , Sepse , Líquido Amniótico , Animais , Humanos , Imunomodulação , Lipopolissacarídeos/toxicidade , Macrófagos Peritoneais , Ratos , Sepse/terapia , Células-Tronco
13.
Stem Cells Transl Med ; 8(11): 1170-1179, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31407874

RESUMO

Despite the poor prognosis associated with myelomeningocele (MMC), the options for prenatal treatments are still limited. Recently, fetal cellular therapy has become a new option for treating birth defects, although the therapeutic effects and mechanisms associated with such treatments remain unclear. The use of human amniotic fluid stem cells (hAFSCs) is ideal with respect to immunoreactivity and cell propagation. The prenatal diagnosis of MMC during early stages of pregnancy could allow for the ex vivo proliferation and modulation of autologous hAFSCs for use in utero stem cell therapy. Therefore, we investigated the therapeutic effects and mechanisms of hAFSCs-based treatment for fetal MMC. hAFSCs were isolated as CD117-positive cells from the amniotic fluid of 15- to 17-week pregnant women who underwent amniocentesis for prenatal diagnosis and consented to this study. Rat dams were exposed to retinoic acid to induce fetal MMC and were subsequently injected with hAFSCs in each amniotic cavity. We measured the exposed area of the spinal cord and hepatocyte growth factor (HGF) levels at the lesion. The exposed spinal area of the hAFSC-treated group was significantly smaller than that of the control group. Immunohistochemical analysis demonstrated a reduction in neuronal damage such as neurodegeneration and astrogliosis in the hAFSC-treated group. Additionally, in lesions of the hAFSC-treated group, HGF expression was upregulated and HGF-positive hAFSCs were identified, suggesting that these cells migrated to the lesion and secreted HGF to suppress neuronal damage and induce neurogenesis. Therefore, in utero hAFSC therapy could become a novel strategy for fetal MMC. Stem Cells Translational Medicine 2019;8:1170-1179.


Assuntos
Líquido Amniótico/citologia , Fator de Crescimento de Hepatócito/metabolismo , Meningomielocele/terapia , Substâncias Protetoras/administração & dosagem , Medula Espinal/metabolismo , Transplante de Células-Tronco/métodos , Células-Tronco/citologia , Líquido Amniótico/metabolismo , Animais , Antineoplásicos/toxicidade , Feminino , Humanos , Meningomielocele/induzido quimicamente , Meningomielocele/patologia , Gravidez , Ratos , Ratos Sprague-Dawley , Células-Tronco/metabolismo , Tretinoína/toxicidade
14.
Pediatr Res ; 85(1): 97-104, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30120407

RESUMO

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) remains a major cause of cerebral palsy. Increasing evidence has suggested that mesenchymal stem cells have a favorable effect on HIE. However, the efficacy of human amniotic fluid stem cells (hAFS) for HIE, especially in the chronic phase, remains unclear. The aim of this study was to determine the neurorestorative effect of hAFS on the chronic phase of HIE. METHODS: hAFS were isolated from AF cells as CD117-positive cells. HI was induced in 9-day-old mice. Animals intranasally received hAFS or phosphate-buffered saline at 10 days post HI and were harvested for histological analysis after functional tests at 21 days post HI. We also implanted PKH26-positive hAFS to assess their migration to the brain. Finally, we determined gene expressions of trophic factors in hAFS co-cultured with HI brain extract. RESULTS: hAFS improved sensorimotor deficits in HIE by gray and white matter restoration and neuroinflammation reduction followed by migration to the lesion. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), hepatocyte growth factor (HGF), and stromal cell-derived factor-1 (SDF-1) gene expressions in hAFS were elevated when exposed to HI-induced brain extract. CONCLUSION: hAFS induced functional recovery by exerting neurorestorative effects in HIE mice, suggesting that intranasal administration of hAFS could be a novel treatment for HIE, especially in the chronic phase.


Assuntos
Líquido Amniótico/citologia , Encéfalo/fisiopatologia , Hipóxia-Isquemia Encefálica/cirurgia , Células-Tronco Neurais/transplante , Neurogênese , Animais , Animais Recém-Nascidos , Comportamento Animal , Encéfalo/metabolismo , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Movimento Celular , Células Cultivadas , Quimiocina CXCL12/metabolismo , Modelos Animais de Doenças , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/patologia , Hipóxia-Isquemia Encefálica/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora , Fator de Crescimento Neural/metabolismo , Células-Tronco Neurais/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Transdução de Sinais
15.
Keio J Med ; 67(4): 57-66, 2018 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-29515049

RESUMO

Mesenchymal stem cells (MSCs) have generated great interest in the fields of regenerative medicine and immunotherapy because of their unique biological properties. Among MSCs, amniotic fluid stem cells (AFS) have a number of characteristics that make them attractive candidates for tissue engineering and cell replacement strategies, particularly for perinatal medicine. If various neonatal conditions, including birth asphyxia, preterm birth, and congenital abnormalities, which result in long-lasting severe impairments, could be predicted during pregnancy, it would allow collection of small samples of amniotic fluid cells by amniocentesis. In vitro culture of these autologous AFS during pregnancy would make them available for use soon after birth. Hypoxic-ischemic encephalopathy (HIE) and myelomeningocele (MMC) are neonatal conditions that cause permanent neurological disability, for which the treatment options are extremely limited. Experiments using animal models of HIE and MMC and human clinical trials have demonstrated that MSCs, including AFS, have beneficial effects on the central nervous system through paracrine influences, indicating that autologous AFS treatment may be applicable for intractable neurological diseases, including HIE and MMC, during the perinatal period. In this review, we focus on recent research related to the therapeutic potential of AFS for perinatal neurological diseases such as HIE and MMC.


Assuntos
Líquido Amniótico/citologia , Hipóxia-Isquemia Encefálica/terapia , Meningomielocele/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Assistência Perinatal/métodos , Amniocentese/métodos , Animais , Sistema Nervoso Central/anormalidades , Sistema Nervoso Central/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/patologia , Masculino , Meningomielocele/metabolismo , Meningomielocele/patologia , Células-Tronco Mesenquimais/metabolismo , Comunicação Parácrina , Gravidez , Ratos , Medicina Regenerativa/métodos , Transplante Autólogo
18.
Int J Gynecol Cancer ; 26(1): 163-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26512787

RESUMO

OBJECTIVE: To investigate pregnancy outcomes in women after abdominal radical trachelectomy (RT) for early-stage cervical cancer. METHODS: The patients' background, fertility, and pregnancy outcomes were reviewed in a total of 61 pregnancies in 48 of 172 women who underwent abdominal RT at Keio University Hospital between September 2002 and December 2013. RESULTS: There were 5 women with stage IA1, 2 with stage IA2, and 41 with stage IB1. Histological types were as follows: squamous cell carcinoma (n = 36), adenocarcinoma (n = 10), and adenosquamous cell carcinoma (n = 2). The pregnancy rate of women attempting to conceive after abdominal RT was 44% (48/109). The mean ± SD duration from abdominal RT to conception was 3.1 ± 1.9 years. Of 61 pregnancies, 42 pregnancies were achieved by fertility treatment (in vitro fertilization-embryo transfer, 39; intrauterine insemination, 3). After excluding one pregnancy without detailed clinical information, there were 42 live births (5 in 22-27 weeks, 11 in 28-33weeks, 20 in 34-36 weeks, and 6 in 37-38 weeks), 13 miscarriages, and 5 ongoing pregnancies. While there were 10 first trimester miscarriages, 3 pregnancies ended in the second trimester owing to chorioamnionitis. The mean gestational age at birth was 33 weeks of pregnancy. Thirty-seven neonates were appropriate-for-date, and one was small-for-date. Six pregnancies exhibited massive bleeding from the residual cervix in the late pregnancy. Preterm birth less than 34 weeks of pregnancy was related to premature rupture of the membrane (P < 0.05). Chorioamnionitis was evident in 9 of 11 pregnancies with preterm premature rupture of the membrane followed by birth at less than 34 weeks of pregnancy. No parturients exhibited lochiometra and endometritis postpartum. CONCLUSIONS: Abdominal RT provided favorable pregnancy outcomes, and fertility treatment could be advantageous to conception. Massive bleeding from the residual cervix as well as ascending infection might be characteristic features during pregnancy after abdominal RT.


Assuntos
Abdome/cirurgia , Adenocarcinoma/cirurgia , Carcinoma Adenoescamoso/cirurgia , Carcinoma de Células Escamosas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Traquelectomia , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/patologia , Adulto , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Gravidez , Resultado da Gravidez , Centros de Atenção Terciária , Fatores de Tempo , Neoplasias do Colo do Útero/patologia
20.
Case Rep Obstet Gynecol ; 2015: 606134, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26491584

RESUMO

Meconium periorchitis is a rare disorder caused by fetal meconium peritonitis, with subsequent passage of meconium into the scrotum via a patent processus vaginalis. To date, clinical significance of meconium periorchitis for the prenatal diagnosis of meconium peritonitis and prediction for postnatal surgery remains to be determined. We present a clinical course of a fetus presenting with meconium periorchitis induced by meconium peritonitis. At 28 weeks' gestation, fetal ultrasonography indicated fetal ascites associated with bilateral hydrocele and peritesticular calcification without other signs of meconium peritonitis. The pregnancy was uneventful until delivery and the infant was delivered at 37 weeks' gestation. No abdominal distension was observed at birth, and radiography did not reveal any abdominal calcification except for scrotal calcification. Abdominal distension was observed 3 days after birth and laparotomy was performed. The diagnosis of meconium peritonitis was confirmed at surgery. Our case illustrated that careful examination of the scrotum during fetal life was helpful for prenatal diagnosis of meconium peritonitis as well as postnatal management.

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