2023
Maternal CXCR4 deletion results in placental defects and pregnancy loss mediated by immune dysregulation
Lyu F, Burzynski C, Fang Y, Tal A, Chen A, Kisa J, Agrawal K, Kluger Y, Taylor H, Tal R. Maternal CXCR4 deletion results in placental defects and pregnancy loss mediated by immune dysregulation. JCI Insight 2023, 8: e172216. PMID: 37815869, PMCID: PMC10721256, DOI: 10.1172/jci.insight.172216.Peer-Reviewed Original ResearchConceptsCXCR4-deficient micePlacental vascular developmentNK cellsCxcr4 deletionNormal placental vascular developmentPlacental developmentNK cell dysfunctionNK cell expressionNK cell infiltrationNK cell functionRole of CXCR4Cell functionMaternal-fetal interfaceImmune cell functionEarly placental developmentWt CXCR4Immune dysregulationVascular developmentGiant cell layerImmune toleranceCXCR4 expressionPeripheral bloodPregnancy failureCell infiltrationPregnancy loss
2022
Chemokine C-X-C receptor 4 mediates recruitment of bone marrow-derived nonhematopoietic and immune cells to the pregnant uterus†
Fang YY, Lyu F, Abuwala N, Tal A, Chen AY, Taylor HS, Tal R. Chemokine C-X-C receptor 4 mediates recruitment of bone marrow-derived nonhematopoietic and immune cells to the pregnant uterus†. Biology Of Reproduction 2022, 106: 1083-1097. PMID: 35134114, PMCID: PMC9198949, DOI: 10.1093/biolre/ioac029.Peer-Reviewed Original ResearchConceptsBone marrow-derived progenitor cellsBM-derived cellsPregnant deciduaPregnant uterusMarrow-derived progenitor cellsC receptor 4Pregnancy-induced increaseRecruitment of boneProgenitor cellsWild-type C57BL/6CXCL12-CXCR4 axisStem/progenitor cellsTamoxifen-inducible CreNK cellsControl miceBM donorsCXCR4 expressionTransgenic GFP miceImmune cellsReceptor 4Nonpregnant uterusChemokine CCXCL12 ligandFemale recipientsSuccessful implantation
2021
Bone Marrow-Derived Progenitor Cells Contribute to Remodeling of the Postpartum Uterus
Tal R, Kisa J, Abuwala N, Kliman HJ, Shaikh S, Chen AY, Lyu F, Taylor HS. Bone Marrow-Derived Progenitor Cells Contribute to Remodeling of the Postpartum Uterus. Stem Cells 2021, 39: 1489-1505. PMID: 34224633, PMCID: PMC9313624, DOI: 10.1002/stem.3431.Peer-Reviewed Original ResearchConceptsPostpartum uterusEndometrial stem/progenitor cellsBone marrow-derived progenitor cellsMarrow-derived progenitor cellsF4/80 macrophage markerUterine tissue regenerationProgenitor cellsC57BL/6J female micePostpartum day 1Cytokeratin-positive epithelial cellsBlood vessel endotheliumStem/progenitor cellsPrepregnancy levelsBM transplantsEndometrial regenerationEndometrial cellsFemale miceMacrophage markersPan-leukocytesLuminal epitheliumBone marrowDay 1BMDCsUterine cellsVessel endotheliumLoss of Cxcr4 in Endometriosis Reduces Proliferation and Lesion Number while Increasing Intraepithelial Lymphocyte Infiltration
Tal A, Tal R, Kliman HJ, Taylor HS. Loss of Cxcr4 in Endometriosis Reduces Proliferation and Lesion Number while Increasing Intraepithelial Lymphocyte Infiltration. American Journal Of Pathology 2021, 191: 1292-1302. PMID: 33964217, PMCID: PMC8261475, DOI: 10.1016/j.ajpath.2021.04.011.Peer-Reviewed Original ResearchConceptsEndometriosis lesionsEpithelial compartmentLesion numberDisruption of CXCR4Intraepithelial lymphocyte infiltrationAdult female miceLoss of CXCR4CXCL12-CXCR4 axisTotal lesion areaProgesterone receptor promoterEndometriosis inductionLymphocyte infiltrationCXCR4 expressionFemale miceHost miceControl lesionsProestrus stageEpithelial proliferationImmune evasionCXCR4LesionsTherapeutic potentialLesion areaReduces ProliferationEpithelial cells
2019
Adult bone marrow progenitors become decidual cells and contribute to embryo implantation and pregnancy
Tal R, Shaikh S, Pallavi P, Tal A, López-Giráldez F, Lyu F, Fang YY, Chinchanikar S, Liu Y, Kliman HJ, Alderman M, Pluchino N, Kayani J, Mamillapalli R, Krause DS, Taylor HS. Adult bone marrow progenitors become decidual cells and contribute to embryo implantation and pregnancy. PLOS Biology 2019, 17: e3000421. PMID: 31513564, PMCID: PMC6742226, DOI: 10.1371/journal.pbio.3000421.Peer-Reviewed Original ResearchConceptsBM transplantsDecidual cellsPregnancy lossMesenchymal stem cellsAdult bone marrow progenitorsDecidualization-related genesBone marrow progenitorsAdult bone marrowWT donorsPhysiologic contributionSuccessful pregnancyBMDC recruitmentStromal expansionImmune cellsEndometrial cellsDeficient miceUterine expressionUterine tissueDecidual stromaPregnancyBone marrowNonhematopoietic cellsBMDCsHemochorial placentaMarrow progenitorsBone-marrow-derived endothelial progenitor cells contribute to vasculogenesis of pregnant mouse uterus†
Tal R, Dong D, Shaikh S, Mamillapalli R, Taylor HS. Bone-marrow-derived endothelial progenitor cells contribute to vasculogenesis of pregnant mouse uterus†. Biology Of Reproduction 2019, 100: 1228-1237. PMID: 30601943, PMCID: PMC6497522, DOI: 10.1093/biolre/ioy265.Peer-Reviewed Original ResearchConceptsEndothelial progenitor cellsPregnant uterusImplantation sitesPregnant miceBM-derived endothelial progenitor cellsProgenitor cellsEarly pregnant uterusUterine implantation sitesContribution of BMNew blood vesselsEndometrial growthBM transplantationEndothelial cell populationEndometrial vasculaturePregnancy maintenanceDecidual vasculatureMouse recipientsGestational dayVascular endotheliumEndothelial-specific promoterBone marrowTransgenic miceMouse deciduaFlow cytometryMice
2018
Characterization of cell fusion in an experimental mouse model of endometriosis†
Tal A, Tal R, Shaikh S, Gidicsin S, Mamillapalli R, Taylor H. Characterization of cell fusion in an experimental mouse model of endometriosis†. Biology Of Reproduction 2018, 100: 390-397. PMID: 30304517, PMCID: PMC7302516, DOI: 10.1093/biolre/ioy221.Peer-Reviewed Original ResearchConceptsMouse modelLimited proliferative activityFunctional endometrial tissueBone marrow transplantation modelExperimental mouse modelEndometrial stem cellsPrincipal cell sourceRepair/regeneration processBone marrow cellsEndometriosis shareCell fusionEndometrial tissueEndometriosis lesionsEndometriotic lesionsUterine cavityTransplantation modelCell fusion eventsCre-lox systemEndometriosisEpithelial markersStromal compartmentLesionsMarrow cellsProliferative activitySca-1Pathway of Maternal Serotonin to the Human Embryo and Fetus
Kliman HJ, Quaratella SB, Setaro AC, Siegman EC, Subha ZT, Tal R, Milano KM, Steck TL. Pathway of Maternal Serotonin to the Human Embryo and Fetus. Endocrinology 2018, 159: 1609-1629. PMID: 29381782, DOI: 10.1210/en.2017-03025.Peer-Reviewed Original ResearchAnimalsATP Binding Cassette Transporter, Subfamily B, Member 1Connexin 43FemaleFetusHumansMaternal-Fetal ExchangeMiceMonoamine OxidaseOctamer Transcription Factor-3PlacentaPregnancyPregnancy Trimester, FirstPregnancy Trimester, SecondSerotoninSerotonin Plasma Membrane Transport ProteinsTrophoblastsTryptophan Hydroxylase
2016
A Murine 5-Fluorouracil-Based Submyeloablation Model for the Study of Bone Marrow-Derived Cell Trafficking in Reproduction
Tal R, Liu Y, Pluchino N, Shaikh S, Mamillapalli R, Taylor H. A Murine 5-Fluorouracil-Based Submyeloablation Model for the Study of Bone Marrow-Derived Cell Trafficking in Reproduction. Endocrinology 2016, 157: 3749-3759. PMID: 27427897, PMCID: PMC6285241, DOI: 10.1210/en.2016-1418.Peer-Reviewed Original ResearchConceptsStem cell factorDonor chimerismOvarian functionBone marrowIntact ovarian functionGreen fluorescent protein miceTransgenic green fluorescent protein (GFP) miceEndometrial regenerationRegimen resultsEndometrial stromaControl miceTransplant modelBM cellsBMDCsCTX-1CD31 stainingImmunohistochemical analysisDay 28Cell traffickingUterine cellsUterusBMTCD45 markersMiceCytometry analysis
2012
The Role of Hypoxia and Hypoxia-Inducible Factor-1Alpha in Preeclampsia Pathogenesis
Tal R. The Role of Hypoxia and Hypoxia-Inducible Factor-1Alpha in Preeclampsia Pathogenesis. Biology Of Reproduction 2012, 87: 134, 1-8. PMID: 23034156, DOI: 10.1095/biolreprod.112.102723.Peer-Reviewed Original ResearchConceptsSoluble fms-like tyrosine kinase-1Pathogenesis of preeclampsiaRole of hypoxiaSoluble endoglinAngiotensin II receptor type IFms-like tyrosine kinase-1Spiral artery remodelingTyrosine kinase-1Hypoxia-inducible factor-1alphaReceptor type IHypoxia-inducible factorMaternal manifestationsPutative culpritsFetal morbiditySymptomatic therapyArtery remodelingPlacental hypoxiaCascade of eventsEndothelin-1Preeclampsia pathogenesisDisease manifestationsPossible molecular linkPreeclampsiaEffective preventionPathogenesis
2010
Effects of Hypoxia-Inducible Factor-1α Overexpression in Pregnant Mice Possible Implications for Preeclampsia and Intrauterine Growth Restriction
Tal R, Shaish A, Barshack I, Polak-Charcon S, Afek A, Volkov A, Feldman B, Avivi C, Harats D. Effects of Hypoxia-Inducible Factor-1α Overexpression in Pregnant Mice Possible Implications for Preeclampsia and Intrauterine Growth Restriction. American Journal Of Pathology 2010, 177: 2950-2962. PMID: 20952590, PMCID: PMC2993274, DOI: 10.2353/ajpath.2010.090800.Peer-Reviewed Original ResearchConceptsIntrauterine growth restrictionHIF-1αControl micePregnant miceGrowth restrictionFetal intrauterine growth restrictionSoluble vascular endothelial growth factor receptor-1Vascular endothelial growth factor receptor 1Serum sFlt-1Elevated liver enzymesLiver enzyme levelsMicroangiopathic hemolytic anemiaPregnancy-specific disorderHypoxia-inducible factor-1αComplete blood countGestational day 8Growth factor receptor 1HIF-1α overexpressionFactor receptor 1Hypoxia-inducible factorPlacental weightPregnant controlsSoluble endoglinBlood pressureSignificant anemia
2008
Specific Induction of Tumor Neovasculature Death by Modified Murine PPE-1 Promoter Armed with HSV-TK
Varda-Bloom N, Hodish I, Shaish A, Greenberger S, Tal R, Feder B, Roitelman J, Breitbart E, Bangio L, Barshack I, Pfeffer R, Harats D. Specific Induction of Tumor Neovasculature Death by Modified Murine PPE-1 Promoter Armed with HSV-TK. Pathobiology 2008, 75: 346-355. PMID: 19096230, DOI: 10.1159/000164219.Peer-Reviewed Original ResearchConceptsHSV-TKSimplex virus thymidine kinaseHSV-TK geneTherapeutic genesVirus thymidine kinaseGene therapyMurine preproendothelin-1 promoterAdenoviral vectorPreproendothelin-1 promoterReporter geneTissue specificityTumor neovasculaturePromoterSpecific inductionGenesHigh expressionTumor angiogenesisMetastasis developmentExpressionNeovasculatureMouse modelKinaseSelectivityEfficiencySpecificityEndothelial-targeted gene transfer of hypoxia-inducible factor-1alpha augments ischemic neovascularization following systemic administration.
Tal R, Shaish A, Rofe K, Feige E, Varda-Bloom N, Afek A, Barshack I, Bangio L, Hodish I, Greenberger S, Peled M, Breitbart E, Harats D. Endothelial-targeted gene transfer of hypoxia-inducible factor-1alpha augments ischemic neovascularization following systemic administration. Molecular Therapy 2008, 16: 1927-36. PMID: 18797451, DOI: 10.1038/mt.2008.191.Peer-Reviewed Original ResearchConceptsHypoxia-inducible factor-1alphaSystemic administrationTherapeutic efficacyProangiogenic gene therapyFactor-1alphaSystemic side effectsEnhanced blood perfusionRoute of administrationTail vein administrationHindlimb ischemia modelMouse hindlimb ischemia modelMurine preproendothelin-1 promoterClinical outcomesPreproendothelin-1 promoterC57BL/6 miceIschemic neovascularizationIntravenous routeIschemic muscleIntraarterial routeIschemia modelCapillary densityIschemic regionSide effectsSystemic toxicityTherapeutic angiogenesisAntiangiogenic systemic gene therapy combined with doxorubicin administration induced caspase 8 and 9-mediated apoptosis in endothelial cells and an anti-metastasis effect
Peled M, Shaish A, Greenberger S, Katav A, Hodish I, Ben-Shushan D, Barshack I, Mendel I, Frishman L, Tal R, Bangio L, Breitbart E, Harats D. Antiangiogenic systemic gene therapy combined with doxorubicin administration induced caspase 8 and 9-mediated apoptosis in endothelial cells and an anti-metastasis effect. Cancer Gene Therapy 2008, 15: 535-542. PMID: 18421310, DOI: 10.1038/cgt.2008.20.Peer-Reviewed Original Research