Background: Retention of fetal bones is a rare cause of abnormal uterine bleeding. Others may present as subfertility, chronic pelvic pain, abnormal vaginal discharge, menometrorrhagia, dysmenorrhea and spontaneous ex...Background: Retention of fetal bones is a rare cause of abnormal uterine bleeding. Others may present as subfertility, chronic pelvic pain, abnormal vaginal discharge, menometrorrhagia, dysmenorrhea and spontaneous expulsion of bony fragments. Incidence is 0.26% among patients undergoing hysteroscopy. Aim: To document a pattern of presentation of retained fetal bone and its management. Case Presentation: Our patient is an 18-year old who presented with vaginal bleeding of four weeks duration and managed for abnormal uterine bleeding due to retained fetal bone following second trimester abortion. Conclusion: The use of transvaginal ultrasound in making diagnosis of retained fetal bone is effective. Treatment by removal of bones through evacuation by dilatation and curettage or hysteroscopy brings about resolution of symptoms. Use of pelvic ultrasonography to confirm complete evacuation of the uterus after abortion especially second trimester abortion could aid in early diagnosis and management of incomplete abortion.展开更多
Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone regeneration.However,current strategies lack regulation of the specific endogenous cell...Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone regeneration.However,current strategies lack regulation of the specific endogenous cell populations for vascularized bone regeneration,thus leading to adverse tissue formation and decreased regenerative efficiency.Here,we engineered a biomaterial to regulate endogenous cell adhesion and promote vascularized bone regeneration.The biomaterial works by presenting two synthetic ligands,LLP2A and LXW7,explicitly targeting integrinsα4β1 andαvβ3,respectively,expressed on the surfaces of the cells related to bone formation and vascularization,such as mesenchymal stem cells(MSCs),osteoblasts,endothelial progenitor cells(EPCs),and endothelial cells(ECs).In vitro,the LLP2A/LXW7 modified biomaterial improved the adhesion of MSCs,osteoblasts,EPCs,and ECs via integrinα4β1 andαvβ3,respectively.In an adult rat calvarial bone defect model,the LLP2A/LXW7 modified biomaterial enhanced bone formation and vascularization by synergistically regulating endogenous cells with osteogenic and angiogenic potentials,such as DLX5^(+)cells,osteocalcin^(+)cells,CD34^(+)/CD45-cells and CD31^(+)cells.In a fetal sheep spinal bone defect model,the LLP2A/LXW7 modified biomaterial augmented bone formation and vascularization without any adverse effects.This innovative biomaterial offers an off-the-shelf,easy-to-use,and biologically safe product suitable for vascularized bone regeneration in both fetal and adult disease environments.展开更多
Mesenchymal stromal cells (MSCs) can be obtained from several sources and the significant differences in their properties make it crucial to investigate the differentiation potential of MSCs from different sources to ...Mesenchymal stromal cells (MSCs) can be obtained from several sources and the significant differences in their properties make it crucial to investigate the differentiation potential of MSCs from different sources to determine the optimal source of MSCs. We investigated if this biological heterogeneity in MSCs from different sources results in different mechanisms for their differentiation. In this study, we compared the gene expression patterns of phenotypically defined MSCs derived from three ontogenically different sources: Embryonic stem cells (hES-MSCs), Fetal limb (Flb-MSCs) and Bone Marrow (BM-MSCs). Differentially expressed genes between differentiated cells and undifferentiated controls were compared across the three MSC sources. We found minimal overlap (5% - 16%) in differentially expressed gene sets among the three sources. Flb-MSCs were similar to BM-MSCs based on differential gene expression patterns. Pathway analysis of the differentially expressed genes using Ingenuity Pathway Analysis (IPA) revealed a large variation in the canonical pathways leading to MSC differentiation. The similar canonical pathways among the three sources were lineage specific. The Flb-MSCs showed maximum overlap of canonical pathways with the BM-MSCs, indicating that the Flb-MSCs are an intermediate source between the less specialised hES-MSC source and the more specialised BM-MSC source. The source specific pathways prove that MSCs from the three ontogenically different sources use different biological pathways to obtain similar differentiation outcomes. Thus our study advocates the understanding of biological pathways to obtain optimal sources of MSCs for various clinical applications.展开更多
The purpose of this study was to assess fetal bovine acellular dermal matrix as a scaffold for supporting the differentiation of bone marrow mesenchymal stem cells into neural cells fol-lowing induction with neural di...The purpose of this study was to assess fetal bovine acellular dermal matrix as a scaffold for supporting the differentiation of bone marrow mesenchymal stem cells into neural cells fol-lowing induction with neural differentiation medium. We performed long-term, continuous observation of cell morphology, growth, differentiation, and neuronal development using several microscopy techniques in conjunction with immunohistochemistry. We examined speciifc neu-ronal proteins and Nissl bodies involved in the differentiation process in order to determine the neuronal differentiation of bone marrow mesenchymal stem cells. The results show that bone marrow mesenchymal stem cells that differentiate on fetal bovine acellular dermal matrix display neuronal morphology with unipolar and bi/multipolar neurite elongations that express neuro-nal-speciifc proteins, includingβIII tubulin. The bone marrow mesenchymal stem cells grown on fetal bovine acellular dermal matrix and induced for long periods of time with neural differen-tiation medium differentiated into a multilayered neural network-like structure with long nerve ifbers that was composed of several parallel microifbers and neuronal cells, forming a complete neural circuit with dendrite-dendrite to axon-dendrite to dendrite-axon synapses. In addition, growth cones with filopodia were observed using scanning electron microscopy. Paraffin sec-tioning showed differentiated bone marrow mesenchymal stem cells with the typical features of neuronal phenotype, such as a large, round nucleus and a cytoplasm full of Nissl bodies. The data suggest that the biological scaffold fetal bovine acellular dermal matrix is capable of supporting human bone marrow mesenchymal stem cell differentiation into functional neurons and the subsequent formation of tissue engineered nerve.展开更多
文摘Background: Retention of fetal bones is a rare cause of abnormal uterine bleeding. Others may present as subfertility, chronic pelvic pain, abnormal vaginal discharge, menometrorrhagia, dysmenorrhea and spontaneous expulsion of bony fragments. Incidence is 0.26% among patients undergoing hysteroscopy. Aim: To document a pattern of presentation of retained fetal bone and its management. Case Presentation: Our patient is an 18-year old who presented with vaginal bleeding of four weeks duration and managed for abnormal uterine bleeding due to retained fetal bone following second trimester abortion. Conclusion: The use of transvaginal ultrasound in making diagnosis of retained fetal bone is effective. Treatment by removal of bones through evacuation by dilatation and curettage or hysteroscopy brings about resolution of symptoms. Use of pelvic ultrasonography to confirm complete evacuation of the uterus after abortion especially second trimester abortion could aid in early diagnosis and management of incomplete abortion.
基金supported by the National Institutes of Health(NIH)grants(5R01NS100761,1R01NS115860)California Institute for Regenerative Medicine(CIRM)grants(CLIN1-11404,CLIN2-12129,TRAN3-13332)+2 种基金the Shriners Hospitals for Children Postdoctoral Fellowship(84705-NCA-19)research grants(85108-NCA-19,85135-NCA-21)Utilization of this Shared Resource was supported by the UC Davis Comprehensive Cancer Center Support Grant awarded by the National Cancer Institute(P30CA093373).
文摘Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone regeneration.However,current strategies lack regulation of the specific endogenous cell populations for vascularized bone regeneration,thus leading to adverse tissue formation and decreased regenerative efficiency.Here,we engineered a biomaterial to regulate endogenous cell adhesion and promote vascularized bone regeneration.The biomaterial works by presenting two synthetic ligands,LLP2A and LXW7,explicitly targeting integrinsα4β1 andαvβ3,respectively,expressed on the surfaces of the cells related to bone formation and vascularization,such as mesenchymal stem cells(MSCs),osteoblasts,endothelial progenitor cells(EPCs),and endothelial cells(ECs).In vitro,the LLP2A/LXW7 modified biomaterial improved the adhesion of MSCs,osteoblasts,EPCs,and ECs via integrinα4β1 andαvβ3,respectively.In an adult rat calvarial bone defect model,the LLP2A/LXW7 modified biomaterial enhanced bone formation and vascularization by synergistically regulating endogenous cells with osteogenic and angiogenic potentials,such as DLX5^(+)cells,osteocalcin^(+)cells,CD34^(+)/CD45-cells and CD31^(+)cells.In a fetal sheep spinal bone defect model,the LLP2A/LXW7 modified biomaterial augmented bone formation and vascularization without any adverse effects.This innovative biomaterial offers an off-the-shelf,easy-to-use,and biologically safe product suitable for vascularized bone regeneration in both fetal and adult disease environments.
文摘Mesenchymal stromal cells (MSCs) can be obtained from several sources and the significant differences in their properties make it crucial to investigate the differentiation potential of MSCs from different sources to determine the optimal source of MSCs. We investigated if this biological heterogeneity in MSCs from different sources results in different mechanisms for their differentiation. In this study, we compared the gene expression patterns of phenotypically defined MSCs derived from three ontogenically different sources: Embryonic stem cells (hES-MSCs), Fetal limb (Flb-MSCs) and Bone Marrow (BM-MSCs). Differentially expressed genes between differentiated cells and undifferentiated controls were compared across the three MSC sources. We found minimal overlap (5% - 16%) in differentially expressed gene sets among the three sources. Flb-MSCs were similar to BM-MSCs based on differential gene expression patterns. Pathway analysis of the differentially expressed genes using Ingenuity Pathway Analysis (IPA) revealed a large variation in the canonical pathways leading to MSC differentiation. The similar canonical pathways among the three sources were lineage specific. The Flb-MSCs showed maximum overlap of canonical pathways with the BM-MSCs, indicating that the Flb-MSCs are an intermediate source between the less specialised hES-MSC source and the more specialised BM-MSC source. The source specific pathways prove that MSCs from the three ontogenically different sources use different biological pathways to obtain similar differentiation outcomes. Thus our study advocates the understanding of biological pathways to obtain optimal sources of MSCs for various clinical applications.
基金supported by a grant from Construction Project of Gansu Provincial Animal Cell Engineering Center,No.0808NTGA013Program for Innovative Research Team in University of Ministry of Education of China,No.IRT13091
文摘The purpose of this study was to assess fetal bovine acellular dermal matrix as a scaffold for supporting the differentiation of bone marrow mesenchymal stem cells into neural cells fol-lowing induction with neural differentiation medium. We performed long-term, continuous observation of cell morphology, growth, differentiation, and neuronal development using several microscopy techniques in conjunction with immunohistochemistry. We examined speciifc neu-ronal proteins and Nissl bodies involved in the differentiation process in order to determine the neuronal differentiation of bone marrow mesenchymal stem cells. The results show that bone marrow mesenchymal stem cells that differentiate on fetal bovine acellular dermal matrix display neuronal morphology with unipolar and bi/multipolar neurite elongations that express neuro-nal-speciifc proteins, includingβIII tubulin. The bone marrow mesenchymal stem cells grown on fetal bovine acellular dermal matrix and induced for long periods of time with neural differen-tiation medium differentiated into a multilayered neural network-like structure with long nerve ifbers that was composed of several parallel microifbers and neuronal cells, forming a complete neural circuit with dendrite-dendrite to axon-dendrite to dendrite-axon synapses. In addition, growth cones with filopodia were observed using scanning electron microscopy. Paraffin sec-tioning showed differentiated bone marrow mesenchymal stem cells with the typical features of neuronal phenotype, such as a large, round nucleus and a cytoplasm full of Nissl bodies. The data suggest that the biological scaffold fetal bovine acellular dermal matrix is capable of supporting human bone marrow mesenchymal stem cell differentiation into functional neurons and the subsequent formation of tissue engineered nerve.
