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Diana W Bianchi - One of the best experts on this subject based on the ideXlab platform.
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circulating Fetal Cell free dna fractions differ in autosomal aneuploidies and monosomy x
Clinical Chemistry, 2014Co-Authors: Richard P Rava, Anupama Srinivasan, Amy J Sehnert, Diana W BianchiAbstract:BACKGROUND: Noninvasive prenatal testing based on massively parallel sequencing (MPS) of Cell-free DNA in maternal plasma has become rapidly integrated into clinical practice for detecting Fetal chromosomal aneuploidy. We directly determined the Fetal fraction (FF) from results obtained with MPS tag counting and examined the relationships of FF to such biological parameters as Fetal karyotype and maternal demographics. METHODS: FF was determined from samples previously collected for the MELISSA (Maternal Blood Is Source to Accurately Diagnose Fetal Aneuploidy) study. Samples were resequenced, analyzed blindly, and aligned to the human genome (assembly hg19). FF was calculated in pregnancies with male or aneuploid fetuses by means of an equation that incorporated the ratio of the tags in these samples to those of a euploid training set. RESULTS: The mean (SD) FF from euploid male pregnancies was 0.126 (0.052) (n = 160). Weak but statistically significant correlations were found between FF and the maternal body mass index ( r 2 = 0.18; P = 2.3 × 10−8) and between FF and gestational age ( r 2 = 0.02; P = 0.047). No relationship with maternal ethnicity or age was observed. Mean FF values for trisomies 21 (n = 90), 18 (n = 38), and 13 (n = 16) and for monosomy X (n = 20) were 0.135 (0.051), 0.089 (0.039), 0.090 (0.062), and 0.106 (0.045), respectively. CONCLUSIONS: MPS tag-count data can be used to determine FF directly and accurately. Compared with male euploid fetuses, the FF is higher in maternal plasma when the fetus has trisomy 21 and is lower when the fetus has trisomy 18, 13, or monosomy X. The different biologies of these aneuploidies have practical implications for the determination of cutoff values, which in turn will affect the diagnostic sensitivity and specificity of the test.
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Comprehensive Analysis of Genes Expressed by Rare Microchimeric Fetal Cells in the Maternal Mouse Lung
Biology of reproduction, 2012Co-Authors: Stephanie Pritchard, Kirby L. Johnson, Heather C. Wick, Donna K. Slonim, Diana W BianchiAbstract:During pregnancy, Cells from each fetus travel into the maternal circulation and organs, resulting in the development of microchimerism. Identification of the Cell types in this microchimeric population would permit better understanding of possible mechanisms by which they affect maternal health. However, comprehensive analysis of Fetal Cells has been hampered by their rarity. In this study, we sought to overcome this obstacle by combining flow cytometry with multidimensional gene expression microarray analysis of Fetal Cells isolated from the murine maternal lung during late pregnancy. Fetal Cells were collected from the lungs of pregnant female mice. cDNA was amplified and hybridized to gene expression microarrays. The resulting Fetal Cell core transcriptome was interrogated using multiple methods including Ingenuity Pathway Analysis, the BioGPS gene expression database, principal component analysis, the Eurexpress gene expression atlas, and primary literature. Here we report that small numbers of Fetal Cells can be flow sorted from the maternal lung, facilitating discovery-driven gene expression analysis. We additionally show that gene expression data can provide functional information about Fetal Cells. Our results suggest that Fetal Cells in the murine maternal lung are a mixed population, consisting of trophoblasts, mesenchymal stem Cells, and Cells of the immune system. Detection of trophoblasts and immune Cells in the maternal lung may facilitate future mechanistic studies related to the development of immune tolerance and pregnancy-related complications, such as pre-eclampsia. Furthermore, the presence and persistence of mesenchymal stem Cells in maternal organs may have implications for long-term postpartum maternal health.
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Fetal Cell Microchimerism and Cancer: A Nexus of Reproduction, Immunology, and Tumor Biology
Cancer research, 2011Co-Authors: Lisa R. Kallenbach, Kirby L. Johnson, Diana W BianchiAbstract:Fetal Cell microchimerism (FCM) is the persistence of Fetal Cells in the maternal circulation and organs following pregnancy. Proposed hypotheses about the function of Fetal Cells in the pathogenesis of maternal cancer include promotion of tumorigenesis, protection by providing immunosurveillance, and participation in tissue repair. To date, studies of FCM and cancer have been primarily descriptive and quantitative. More research is needed to understand the Cellular phenotype of the microchimeric Cells in maternal tumors and whether they have a functional role. This research will require further study using a multidisciplinary approach, incorporating knowledge of the fetomaternal relationship, tumor biology, immunology, and clinical oncology.
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Fetal Cells in the Pregnant Mouse Are Diverse and Express a Variety of Progenitor and Differentiated Cell Markers
Biology of reproduction, 2009Co-Authors: Yutaka Fujiki, Inga Peter, Kirby L. Johnson, Hocine Tighiouart, Diana W BianchiAbstract:To better understand fetomaternal Cell trafficking during pregnancy, we used a mouse model to determine the Cell surface markers expressed on Fetal Cells, based on the hypothesis that Fetal progenitor Cells have the capacity to repair maternal organs, whereas more differentiated Cells might initiate graft versus host disease. Wild-type females were mated to either homozygous or hemizygous transgenic males and euthanized in the peripartum period. Using dual color flow cytometry, we analyzed Fetal transgene positive Cells for the presence of nine markers (ITGAM, ITGB1, PECAM, CD34, CD44, PTPRC, ENG, SLAMF1, and CXCR4) to begin to identify the phenotype and degree of differentiation of Fetal Cells in nine maternal organs (lung, liver, spleen, blood, bone marrow, kidney, heart, thymus, and brain). Fetal Cells were found in all maternal organs following either type of mating, albeit always at a higher frequency following mating with homozygous males. Some organs (e.g., lung and liver) had a wide variety of Fetal Cell markers present, while other organs (e.g., bone marrow and spleen) had a skewed distribution of Fetal Cell markers. Fetal Cells in the murine pregnant female are diverse. Our results suggest that the Fetal Cells comprise a mixed population of progenitor and differentiated Cells, with different relative proportions in different maternal organs. Future studies will address whether Fetal Cells cross the placental barrier in a differentiated state or as a homogenous population and subsequently differentiate in target maternal organs.
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Fetal Cells participate over time in the response to specific types of murine maternal hepatic injury
Human reproduction (Oxford England), 2006Co-Authors: Kiarash Khosrotehrani, Kirby L. Johnson, Sarah Guégan, Helene Stroh, R.r. Reyes, Richard B. Freeman, Robert N. Salomon, Inga Peter, Diana W BianchiAbstract:In humans, Fetal microchimeric Cells transferred to maternal tissues during pregnancy can adopt a hepatocyte phenotype. Our objective was to determine whether Fetal Cells participate in the response to specific murine post-partum hepatic injuries. Wild-type female mice were bred to males transgenic for the enhanced green fluorescent protein (GFP) (n = 42). Following delivery, we created models of chemical or surgical injury with carbon tetrachloride (CCl(4)) injection or by performing partial hepatectomy. Liver injury was assessed histologically. Fetal Cells in maternal liver were detected and measured by real-time PCR amplification of the gfp transgene and by immunofluorescence using anti-GFP antibodies. PCR results showed that in chemical but not surgical injury, Fetal GFP+ Cells were detectable in maternal liver and spleen and that Fetal Cell presence was significantly increased over time following injury (4 versus 8 weeks, P = 0.006 for liver and P = 0.0006 for spleen). In some animals, following chemical injury, GFP+ Cells were detected by immunofluorescence. The results of this preliminary study suggest that specific types of injury may elicit different Fetal Cell responses in maternal organs. There is a significant effect of time on Fetal Cell presence in liver and spleen. Furthermore, real-time PCR amplification is more sensitive than immunofluorescence for the detection of microchimeric Fetal Cells.
Dario O. Fauza - One of the best experts on this subject based on the ideXlab platform.
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Fetal tissue engineering.
Clinics in Perinatology, 2009Co-Authors: Christopher G. Turner, Dario O. FauzaAbstract:Although numerous properties and therapeutic applications of Fetal Cells/tissues have been explored experimentally or clinically for decades, Fetal tissue engineering is a fairly recent concept. It involves the procurement of Fetal Cells, which are then processed to engineer tissue in parallel to the remainder of gestation, so that an infant, or a fetus, with a prenatally diagnosed birth defect can benefit from having autologous, expanded tissue readily available for surgical implantation before or after birth. Fetal annexes such as the amniotic fluid, placenta, and umbilical cord have been shown to provide minimally invasive access to unique Fetal progenitor Cell populations that are quite conducive to tissue engineering. Despite encouraging results in large animal models, controlled clinical trials involving Fetal tissue engineering have yet to be reported. At the same time, it has been shown experimentally that many complications of tissue engineering can be better managed, if not totally prevented, when Fetal Cells are used. Compared with mature Cells, Fetal Cells have multiple properties that render them better options for tissue engineering, such as the fact that they typically proliferate more rapidly, are more plastic in their differentiation potential, frequently produce more angiogenic and trophic factors, tend to be less immunogenic, can survive at lower oxygen tensions, commonly lack strong interCellular adhesions, and display better survival after refrigeration and cryopreservation protocols. Further, the developmental and long-term impacts of tissue implantations into a fetus or neonate are unmatched by implantations in most other age groups. This chapter offers an overview of Fetal tissue engineering as a perinatal therapeutic concept, along with general perspectives on Fetal Cell and tissue transplantation.
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Fetal tissue engineering.
Clinics in perinatology, 2009Co-Authors: Christopher G. Turner, Dario O. FauzaAbstract:Attempts at harnessing the prospective benefits of the therapeutic use of Fetal Cells or tissues date many decades before the modern era of transplantation. The first reported transplantation of human Fetal tissue took place in 1922. Fetal Cells or tissues also have been used as helpful investigational tools since the 1930s. Still, it was only in the last three decades that Fetal tissue transplantation in people has started to lead to favorable outcomes, yet by and large anecdotally. This article offers an outlook on a relatively new dimension in Fetal Cell-based therapies, namely the engineering of tissues in the laboratory, along with its prospective applications.
Kiarash Khosrotehrani - One of the best experts on this subject based on the ideXlab platform.
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Fetal-Cell microchimerism, lymphopoiesis, and autoimmunity
Archivum immunologiae et therapiae experimentalis, 2009Co-Authors: Michèle Leduc, Selim Aractingi, Kiarash KhosrotehraniAbstract:During all human and murine pregnancies, Fetal Cells enter the maternal circulation and tissues and may persist there for decades. The immune consequences of this phenomenon have been explored for many years as a potential origin of autoimmunity or protection from cancer in women after pregnancy. The leading hypothesis, suggesting that semi-allogenic Fetal T Cells may trigger a graft-versus-host type of disease, has been supported by several studies showing an increased frequency of Fetal-Cell microchimerism (FMc) in women affected with systemic sclerosis. However, a large proportion of healthy women or women affected with non-immune disorders also display Fetal T Cells, challenging the direct pathogenic role of such Cells. In addition, recent evidence showing the transfer of various Fetal progenitor Cells to the mother during gestation has shed new light on the interpretation of microchimerism in autoimmunity. This review discusses the functional capacity of Fetal hematopoietic progenitors to form T and B Cells in maternal hematopoietic tissues, where they undergo an educational process probably resulting in tolerance to maternal antigens. Therefore, hypotheses other than the transfer of Fetal Cells to the mother’s circulation should be considered in explaining the observed association of FMc and autoimmune disorders.
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Increased Fetal Cell microchimerism in high grade breast carcinomas occurring during pregnancy.
International journal of cancer, 2009Co-Authors: Gil Dubernard, Selim Aractingi, M. Oster, Fabrice Chareyre, Martine Antoine, Roman Rouzier, Serge Uzan, Kiarash KhosrotehraniAbstract:Pregnancy results in the transfer of stem Cells from the fetus to the maternal circulation. These Cells are able to migrate and differentiate within various damaged maternal tissues. We recently showed the presence of Fetal-derived Cells in human breast carcinomas during pregnancy. In this study, we aimed to reproduce these results in a murine model of pregnancy-associated breast carcinoma. We bred virgin MMTV-H-Ras transgenic female mice with male mice transgenic for luciferase under the control of the VEGFR2 promoter. Tumors that developed during or following gestation were analyzed and their nuclear grade classified. Fetal Cells were detected by Y chromosome Fluorescence in situ hybridization FISH in 9/9 of breast carcinomas but only in 2 liver controls from the same animals. The number of Fetal Cells was 20 and 4.9 per million maternal Cells in these tissues, respectively (p < 0.05). High grade tumors had significantly more Fetal Cells (p < 0.05). In vivo imaging of the luciferase signal under control of the VEGFR2 promoter as well as von Willebrand staining did not reveal an endothelial phenotype of Fetal Cells. Sixty two percent of the Fetal Cells expressed cytokeratins but were not tumoral. In conclusion, Fetal Cells - expressing cytokeratin - are always present in murine breast carcinomas associated with gestation. Interestingly, high-grade tumors contain more Fetal Cells.
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Fetal Cell microchimerism in cancer: a meaningful event?
Future oncology (London England), 2009Co-Authors: Kiarash Khosrotehrani, Selim AractingiAbstract:The influence of pregnancy on the occurrence and evolution of maternal tumors has been long debated. Breast carcinomas or melanomas have been suspected to be more severe during gestation. Recently, many investigators have described the transfer and persistence of Fetal Cells in maternal circulation and tissues during and after pregnancy. These Fetal microchimeric Cells have been described in a variety of maternal injured tissues where they displayed the host-tissue phenotype. Given the wide variety of injury and tissue types described, cancer has appeared as a potential situation that could be influenced by Fetal microchimeric Cells. This new unexplored effect of gestation on tumor course has been hypothesized as either protective against cancer, via the activity of allogenic Fetal Cells, or as promoting cancer, via a supportive role of Fetal microchimeric Cells in the tumor stroma. In this review, we will detail recent data supporting these hypotheses.
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Fetal Cells participate over time in the response to specific types of murine maternal hepatic injury
Human reproduction (Oxford England), 2006Co-Authors: Kiarash Khosrotehrani, Kirby L. Johnson, Sarah Guégan, Helene Stroh, R.r. Reyes, Richard B. Freeman, Robert N. Salomon, Inga Peter, Diana W BianchiAbstract:In humans, Fetal microchimeric Cells transferred to maternal tissues during pregnancy can adopt a hepatocyte phenotype. Our objective was to determine whether Fetal Cells participate in the response to specific murine post-partum hepatic injuries. Wild-type female mice were bred to males transgenic for the enhanced green fluorescent protein (GFP) (n = 42). Following delivery, we created models of chemical or surgical injury with carbon tetrachloride (CCl(4)) injection or by performing partial hepatectomy. Liver injury was assessed histologically. Fetal Cells in maternal liver were detected and measured by real-time PCR amplification of the gfp transgene and by immunofluorescence using anti-GFP antibodies. PCR results showed that in chemical but not surgical injury, Fetal GFP+ Cells were detectable in maternal liver and spleen and that Fetal Cell presence was significantly increased over time following injury (4 versus 8 weeks, P = 0.006 for liver and P = 0.0006 for spleen). In some animals, following chemical injury, GFP+ Cells were detected by immunofluorescence. The results of this preliminary study suggest that specific types of injury may elicit different Fetal Cell responses in maternal organs. There is a significant effect of time on Fetal Cell presence in liver and spleen. Furthermore, real-time PCR amplification is more sensitive than immunofluorescence for the detection of microchimeric Fetal Cells.
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Multi-lineage potential of Fetal Cells in maternal tissue: a legacy in reverse.
Journal of cell science, 2005Co-Authors: Kiarash Khosrotehrani, Diana W BianchiAbstract:Fetal Cells circulate in pregnant women and persist in blood and tissue for decades post-partum. The mother thus becomes chimeric. Factors that may influence such Fetal Cell microchimerism include histocompatibility, Fetal or placental abnormalities, or a reproductive history that includes miscarriage or elective termination. Fetal Cell microchimerism is associated with some maternal autoimmune diseases, such as systemic sclerosis. Moreover, a novel population of Fetal Cells, the pregnancy-associated progenitor Cells (PAPCs), appears to differentiate in diseased or injured maternal tissue. The Cellular origin of these Cells is at present unknown but could be a hematopoietic stem Cell, a mesenchymal stem Cell, or a novel Cell type. Pregnancy therefore results in the acquisition of Cells with stem-Cell-like properties that may influence maternal health post-partum. Rather than triggering disease, these Cells may instead combat it.
Christopher G. Turner - One of the best experts on this subject based on the ideXlab platform.
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Fetal tissue engineering.
Clinics in Perinatology, 2009Co-Authors: Christopher G. Turner, Dario O. FauzaAbstract:Although numerous properties and therapeutic applications of Fetal Cells/tissues have been explored experimentally or clinically for decades, Fetal tissue engineering is a fairly recent concept. It involves the procurement of Fetal Cells, which are then processed to engineer tissue in parallel to the remainder of gestation, so that an infant, or a fetus, with a prenatally diagnosed birth defect can benefit from having autologous, expanded tissue readily available for surgical implantation before or after birth. Fetal annexes such as the amniotic fluid, placenta, and umbilical cord have been shown to provide minimally invasive access to unique Fetal progenitor Cell populations that are quite conducive to tissue engineering. Despite encouraging results in large animal models, controlled clinical trials involving Fetal tissue engineering have yet to be reported. At the same time, it has been shown experimentally that many complications of tissue engineering can be better managed, if not totally prevented, when Fetal Cells are used. Compared with mature Cells, Fetal Cells have multiple properties that render them better options for tissue engineering, such as the fact that they typically proliferate more rapidly, are more plastic in their differentiation potential, frequently produce more angiogenic and trophic factors, tend to be less immunogenic, can survive at lower oxygen tensions, commonly lack strong interCellular adhesions, and display better survival after refrigeration and cryopreservation protocols. Further, the developmental and long-term impacts of tissue implantations into a fetus or neonate are unmatched by implantations in most other age groups. This chapter offers an overview of Fetal tissue engineering as a perinatal therapeutic concept, along with general perspectives on Fetal Cell and tissue transplantation.
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Fetal tissue engineering.
Clinics in perinatology, 2009Co-Authors: Christopher G. Turner, Dario O. FauzaAbstract:Attempts at harnessing the prospective benefits of the therapeutic use of Fetal Cells or tissues date many decades before the modern era of transplantation. The first reported transplantation of human Fetal tissue took place in 1922. Fetal Cells or tissues also have been used as helpful investigational tools since the 1930s. Still, it was only in the last three decades that Fetal tissue transplantation in people has started to lead to favorable outcomes, yet by and large anecdotally. This article offers an outlook on a relatively new dimension in Fetal Cell-based therapies, namely the engineering of tissues in the laboratory, along with its prospective applications.
Mary Ann Demaria - One of the best experts on this subject based on the ideXlab platform.
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DEVELOPMENT OF A MODEL SYSTEM TO COMPARE Cell SEPARATION METHODS FOR THE ISOLATION OF Fetal CellS FROM MATERNAL BLOOD
Prenatal diagnosis, 1996Co-Authors: Diana W Bianchi, Katherine W Klinger, Anthony P Shuber, Theresa J. Vadnais, Mary Ann Demaria, Joel Skoletsky, Pat Midura, Matthew Diriso, Christine Pelletier, Michelle GenovaAbstract:Three major methods have been described for the isolation of Fetal Cells from maternal blood : fluorescence-activated Cell sorting (FACS), immunomagnetic beads, and magnetic-activated Cell sorting (MACS). To date, no study has directly compared Fetal Cell recovery using each of these methods. Here we describe out system using a 'model' male Fetal Cell mixed into female peripheral blood mononuclear Cells. Fetal Cell yields and purities were assayed by a quantitative polymerase chain reaction (qPCR) using chromosomes Y- and 7-specific sequences. Fetal Cell recovery was investigated by selection of CD71 + Cells or depletion of CD45 + Cells. Out data demonstrated variation in Fetal Cell recovery for all methods tested, although CD71 + selection by FACS gave the best and most consistent results.
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Fetal RhD genotyping in Fetal Cells flow sorted from maternal blood
American journal of obstetrics and gynecology, 1996Co-Authors: Ossie Geifman-holtzman, Theresa J. Vadnais, Mary Ann Demaria, Ira M. Bernstein, Stanley M. Berry, E J Holtzman, Diana W BianchiAbstract:The aim of this study was to determine the accuracy of noninvasive Fetal RhD genotyping by Fetal Cell isolation from maternal blood. Candidate Fetal Cells from 18 pregnant women (one twin gestation) were flow-sorted. Polymerase chain reaction amplification of a 261 bp fragment of the RhD gene was performed on sorted Fetal Cells. The presence of amplified product was considered predictive of the Rhd-positive genotype in the fetus. Sixteen of the 19 Fetal RhD genotypes were correctly predicted in Fetal Cells isolated from maternal blood (10 were Rh positive, 6 were Rh negative). In 3 cases no amplification products were detected in RhD-positive fetuses. The association between presence of the fragment and RhD-positive genotype was significant (p=0.003, Fisher's exact test). Noninvasive prenatal diagnosis of the Fetal RhD genotype is feasible. Absence of amplification products in the reaction requires confirmation that Fetal material is present. Improvements in Fetal Cell purity and yield should increase diagnostic accuracy, although the current protocol has a positive predictive value of 100% and a negative predictive value of 67%.
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Fetal Cells in maternal blood: determination of purity and yield by quantitative polymerase chain reaction.
American journal of obstetrics and gynecology, 1994Co-Authors: Diana W Bianchi, Anthony P Shuber, Mary Ann Demaria, Arthur C. Fougner, Katherine W KlingerAbstract:Abstract Objective: The detection of Fetal aneuploidy and gene mutations by analysis of Fetal Cells in maternal blood has demonstrated the feasibility of noninvasive prenatal diagnosis. Fetal Cells are rare in the maternal circulation; all current methods used for their isolation also yield maternal Cells. We developed a method that permits a quantitative assessment of the relative numbers of Fetal and maternal Cells. Study Design: Samples from 40 pregnant women were flow sorted with different monoclonal antibodies. Deoxyribonucleic acid was subsequently purified from candidate Fetal Cells; polymerase chain reaction was performed with synthetic primers specific for sequences on chromosomes Y and 7. Results: The maximum number of Fetal Cells detected was 52 in 1080 maternal Cells. Fetal Cell purity ranged from 0.001 % to 4.8%. Fetal Cells were detected with antibodies to CD71, CD36, and glycophorin A. Conclusion: Quantitative polymerase chain reaction enables the determination of the purity and yield of Fetal Cells remaining after isolation from maternal blood, facilitating rapid comparisons between different Cell separation techniques.