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1.
Rev. cuba. hematol. inmunol. hemoter ; 36(3): e1172, jul.-set. 2020. graf
Article in Spanish | LILACS, CUMED | ID: biblio-1156436

ABSTRACT

Introducción: Las leucemias agudas de linaje ambiguo constituyen un grupo heterogéneo de leucemias agudas que no muestran una evidencia clara de diferenciación a lo largo del linaje celular. El diagnóstico definitivo se realiza exclusivamente por las características inmunofenotípicas, con el uso de la citometría de flujo multiparamétrica. Objetivo: Actualizar los criterios diagnósticos, la clasificación, el manejo clínico y terapéutico de las leucemias agudas de linaje ambiguo. Métodos: Se realizó una búsqueda de información científica relacionada con el tema en libros de textos de Hematología Clínica y en artículos publicados a través de PUBMED en los últimos 10 años. Se hizo un análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: Las características morfológicas de las células leucémicas procedentes de los pacientes con leucemias agudas de linaje ambiguo no muestran uniformidad. Pueden encontrarse de forma simultánea blastos de diferentes tamaños y estados de maduración. Estos pueden presentar apariencia linfoide, mieloide, indiferenciada o mixta. Conclusión: Las leucemias agudas de linaje ambiguo constituyen un subgrupo de alto riesgo, con un pronóstico desfavorable y una pobre supervivencia global de los enfermos. Su reporte oportuno es indispensable para aunar los criterios de la toma de decisiones terapéuticas en este grupo de pacientes(AU)


Introduction: Acute leukemias of ambiguous lineage constitute a heterogeneous group of acute leukemias that do not show clear evidence of differentiation along cell lineage. The definitive diagnosis is made exclusively based on immunophenotypic characteristics, with the use of multiparametric flow cytometry. Objective: To update the diagnostic criteria, classification, as well as the clinical and therapeutic management of acute leukemias of ambiguous lineage. Methods: A search for scientific information related to the subject was carried out in clinical hematology textbooks and in articles published through PUBMED in the last ten years. An analysis and summary of the revised bibliography was carried out. Information analysis and synthesis: The morphological characteristics of the leukemic cells from patients with acute leukemia of ambiguous lineage do not show uniformity. Blasts of different sizes and stages of maturation can be found simultaneously. These may appear as lymphoid, myeloid, undifferentiated, or mixed. Conclusion: Acute leukemias of ambiguous lineage constitute a high-risk subgroup, with unfavorable prognosis and poor overall patient survival. Its timely report is essential to gather criteria for making therapeutic decisions in this group of patients(AU)


Subject(s)
Humans , Prognosis , Leukemia/diagnosis , Cell Lineage/genetics , Flow Cytometry , Survivorship , Leukemia/therapy
2.
Journal of Experimental Hematology ; (6): 1044-1048, 2020.
Article in Chinese | WPRIM | ID: wpr-827164

ABSTRACT

Abstract  Hematopoietic stem cells are able to self-renewal and differentiate to all blood lineages. With the development of new technologies, recent studies have proposed the revised versions of hematopoiesis. In the classical model of hematopoietic differentiation, HSCs were located at the apex of hematopoietic hierarchy. During differentiation process, HSCs progressively lose self-renewal potential to be commited to progenitors with restricted differentiation potential. For instance, HSCs first give rise to multipotent progenitor cells, then produce bipotent and unipotent progenitors, and finally differentiate to mature blood cells. For the differentiation of megakaryocytes, common myeloid progenitors derived from HSCs give rise to megakaryocyte-erythrocyte progenitors and then develop to megakaryocytes. However, recent results show that megakaryocytes can be directly generated from HSCs without multipotent or bipotent phases. Alternatively, platelet-biased HSCs produce megakaryocyte progenitors. In this article, recent advances in the hematopoiesis and megakaryocyte differentiation pathway are reviewed.


Subject(s)
Cell Differentiation , Cell Lineage , Hematopoiesis , Hematopoietic Stem Cells , Megakaryocytes , Multipotent Stem Cells
3.
Protein & Cell ; (12): 740-770, 2020.
Article in English | WPRIM | ID: wpr-827016

ABSTRACT

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.


Subject(s)
Adult , Aged , Aged, 80 and over , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Humans , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Middle Aged , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , Transcriptome , Young Adult
4.
Annals of Dermatology ; : 130-140, 2020.
Article in English | WPRIM | ID: wpr-811085

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is recognized as a common inflammatory skin disease and frequently occurred in Asian and Black individuals.OBJECTIVE: Since the limitation of dataset associated with human severe AD, this study aimed to screen potential novel biomarkers involved in mild AD.METHODS: Expression profile data (GSE75890) were obtained from the database of Gene Expression Omnibus. Using limma package, the differentially expressed genes (DEGs) between samples from AD and healthy control were selected. Furthermore, function analysis was conducted. Meanwhile, the protein-protein interaction (PPI) network and transcription factor (TF)-miRNA-target regulatory network were constructed. And quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the expressions patterns of key genes.RESULTS: In total, 285 DEGs including 214 upregulated and 71 downregulated genes were identified between samples from two groups. The upregulated DEGs were mainly involved in nine pathways, such as hematopoietic cell lineage, pertussis, p53 signaling pathway, staphylococcus aureus infection, and cell cycle, while tight junction was the only pathway enriched by the downregulated DEGs. Cyclin B (CCNB)1, CCNB2, cyclin A (CCNA)2, C-X-C motif chemokine ligand (CXCL)10, and CXCL9 were key nodes in PPI network. The TF-miRNA-target gene regulatory network focused on miRNAs such as miR-106b, miR-106a, and miR-17, TFs such as nuclear factor kappa B subunit 1, RELA proto-oncogene, Sp1 transcription factor, and genes such as matrix metallopeptidase 9, peroxisome proliferator activated receptor gamma , and serpin family E member 1. Moreover, the upregulation of these genes, including CCNB1, CCNB2, CCNA2, CXCL10, and CXCL9 were confirmed by qRT-PCR.CONCLUSION: CCNB1, CCNB2, CCNA2, and CXCL9 might be novel markers of mild AD. miR-106b and miR-17 may involve in regulation of immune response in AD patients.


Subject(s)
Asian Continental Ancestry Group , Biomarkers , Cell Cycle , Cell Lineage , Computational Biology , Cyclin A , Cyclin B , Dataset , Dermatitis , Dermatitis, Atopic , Gene Expression , Gene Regulatory Networks , Humans , MicroRNAs , NF-kappa B , PPAR gamma , Proto-Oncogenes , Real-Time Polymerase Chain Reaction , Skin Diseases , Sp1 Transcription Factor , Staphylococcus aureus , Tight Junctions , Transcription Factors , Up-Regulation , Whooping Cough
5.
Protein & Cell ; (12): 740-770, 2020.
Article in English | WPRIM | ID: wpr-828746

ABSTRACT

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.


Subject(s)
Adult , Aged , Aged, 80 and over , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Humans , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Middle Aged , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , Transcriptome , Young Adult
6.
Protein & Cell ; (12): 740-770, 2020.
Article in English | WPRIM | ID: wpr-828582

ABSTRACT

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.


Subject(s)
Adult , Aged , Aged, 80 and over , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Humans , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Middle Aged , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , Transcriptome , Young Adult
7.
Article in Chinese | WPRIM | ID: wpr-771857

ABSTRACT

OBJECTIVE@#To understand the differentiation of mesoderm-derived Flk1 cells on different locations of the early mouse embryonic development and to explore the potential of Flk1 cells to differentiate into mesenchymal lineage, like pericytes during vascular development.@*METHODS@#Based on the Cre-LoxP system conditional knockout study strategy, the Flk1-Cre mice and ROSA26 reporter mice were used for lineage-tracing studies. The fate of the Flk1 progenitor cells was traced with the GFP population. The detection of mesoderm marker Flk1, hematopoietic cell-specific marker CD45, endothelial cell-specific markers CD31, CD144, and Emcn (endomucin), pericyte specific markers PDGFRβ and NG2, using the methods of immunohistochemistry, immunofluorescence, and flow cytometry should be combined to solve the concerned problems.@*RESULTS@#Immunohistochemical staining of different fractions of E8.5-10.5 in the early embryogenesis of Flk1-Cre; ROSA26-EYFP mouse lineage showed that there were multiple populations in the Flk1 cell-derived GFP population surrounding hematopoietic sites, such as dorsal aortas, limb buds and yolk sac. In addition to hematopoietic cells, the CD31/Emcn typical endothelial cells distributed specifically along the blood vessel wall, there were many types of cell populations, such as mesenchymal-like cells. The immunofluorescence demonstrated that the cells of this group are neither hematopoietic, non-endothelial cells around the blood vessels, which are NG2+ pericytes. FACS analysis also confirmed that Flk1 cells contributed to pericytes. In addition, in different hematopoietic sites of the embryo, a small population of CD31+CD140B+ cell populations with a mesenchymal-like morphology was observed in the GFP population.@*CONCLUSION@#In the early stages of embryogenesis, mesoderm-derived Flk1 populations not only contribute to hematopoietic, endothelial, and muscle lineages, but also have a differentiation potential for mesenchymal lineage, like pericytes. The presumably observed CD31CD140B cell population may be a group of endothelial cells differentiated from Flk1 progenitor cells and undergoing an endothelium-to-mesenchymal transition, EndMT, gradually losing the endothelial surface-specific marker and also starting to express a pericyte surface-specific marker.


Subject(s)
Animals , Cell Differentiation , Cell Lineage , Mesoderm , Mice , Stem Cells , Vascular Endothelial Growth Factor Receptor-2 , Yolk Sac
8.
Article in English | WPRIM | ID: wpr-771429

ABSTRACT

OBJECTIVE@#To explore the effect of Qinghuang Powder (QHP,()combined with Bupi Yishen Decoction (BPYS, ) on myelodysplastic syndromes (MDS) patients with refractory cytopenia with multilineage dysplasia (RCMD) and determine the change of DNA methylation in MDS-RCMD patients after the treatment of Chinese medicine formula.@*METHODS@#All 308 MDS-RCMD patients were treated with QHP combined with BPYS for 2 months at least, absolute neutrophil count (ANC), hemoglobin (Hb), platelets (PLT), primitive bone marrow cells and chromosome karyotype were chosen as the main evaluation indexes to analyze the treatment effect according to criteria from the MDS International Working Group. Then 43 bone marrow samples from 15 MDS-RCMD patients and 28 healthy donors were obtained for the examination of DNA methylation. Gene Ontology (GO) and Pathway analysis were applied to analyze the methylation data.@*RESULTS@#The overall MDS response rate to QHP was 61.68% (190/360) including hematologic improvement-neutrophil (HI-N) or hematologic improvement-erythroid (HI-E) or hematologic improvement-platelet (HI-P). Patients with anemia had a better response rate than patients with neutropenia or thrombocypenia (55.88% vs 31.54% or 55.88% vs. 36.9%). The DNA methylation microarray analysis disclosed that 4,257 hypermethylated genes were demethylated upon the treatment with QHP and BPYS. GO analysis and Pathway analysis showed that these demethylated genes were involved in a lot of tumor-related pathways and functions.@*CONCLUSIONS@#QHP combined with BPYS could effectively treat MDS-RCMD patients through hematologic improvement (HI-N, HI-P or HI-E) and PLT and RBC transfusion independence due to the demethylation, thereby providing another choice for the treatment of patients with MDS-RCMD.


Subject(s)
Arsenicals , Pharmacology , Therapeutic Uses , Cell Lineage , DNA Methylation , Demethylation , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Female , Gene Ontology , Humans , Leukocyte Disorders , Drug Therapy , Genetics , Male , Middle Aged , Powders , Treatment Outcome
9.
Journal of Experimental Hematology ; (6): 1744-1748, 2019.
Article in Chinese | WPRIM | ID: wpr-781403

ABSTRACT

OBJECTIVE@#To analyze the effect of down-regulating the CD59 gene expression by RNAi lentivirus as vector on Jurkat cell line of acute T-lineage leukemia.@*METHODS@#The expression of CD59 in Jurkat cell line of acute T-line leukemia was induced to decrease by RNAi lentivirus as vector. The transfection of RNA lentivirus and the localization of CD59 molecule were analyzed by laser confocal technique. The relative expression of CD59 gene in blank control, negative control and RNAi lentivirus transfected group was detected by real-time fluorescence quantitative PCR, and the enzyme-linked immunosorbent assay was used to detect the expression of TNF-β and IL-3 in supernatants of cultured cells in 3 groups. The expression levels of apoptosis-related molecules including Caspase-3, Survivin, BCL-2 and BCL-2-associated X protein (BAX) were measured by Western blot.@*RESULTS@#The transfection efficiency for Jurkat cells was higher than 90%. CD59 was mainly located on the cell membrane. Compared with the blank control group and the negative control group, the expression level of CD59 mRNA and protein in the RNAi lentivirus transfected group significantly decreased (P<0.05). Compared with the blank control group and the negative control group, the expression of TNF-β and IL-3 in the RNAi lentivirus transfected group were significantly higher and lower (P<0.05) respectively. The expression levels of Survivin and BCL-2 in the RNAi lentivirus transfected group were significantly lower than those in the blank control group and the negative control group, while the expression levels of Caspase-3 and BAX in the RNAi lentivirus transfected group were significantly higher than those in the blank control group and the negative control group (P< 0.05).@*CONCLUSION@#The down-regulation of CD59 gene expression induced by RNAi lenti-virus can decrease the expression of proliferation and differentiation-promoting molecule such as IL-3 and increase the expression of TNF-related factor in Jurkat cell line of acute T-lineage leukemia, which also can increase the expression of apoptosis-related proteins such as Caspase-3 and BAX, and decrease the expression of anti-apoptosis-related proteins such as Survivin and BCL-2.


Subject(s)
Apoptosis , CD59 Antigens , Cell Lineage , Cell Proliferation , Down-Regulation , Humans , Jurkat Cells , Lentivirus , Leukemia , RNA Interference , RNA, Small Interfering , Transfection
10.
Neuroscience Bulletin ; (6): 145-155, 2019.
Article in English | WPRIM | ID: wpr-775481

ABSTRACT

The autonomic nervous system controls various internal organs and executes crucial functions through sophisticated neural connectivity and circuits. Its dysfunction causes an imbalance of homeostasis and numerous human disorders. In the past decades, great efforts have been made to study the structure and functions of this system, but so far, our understanding of the classification of autonomic neuronal subpopulations remains limited and a precise map of their connectivity has not been achieved. One of the major challenges that hinder rapid progress in these areas is the complexity and heterogeneity of autonomic neurons. To facilitate the identification of neuronal subgroups in the autonomic nervous system, here we review the well-established and cutting-edge technologies that are frequently used in peripheral neuronal tracing and profiling, and discuss their operating mechanisms, advantages, and targeted applications.


Subject(s)
Animals , Autonomic Nervous System , Physiology , Cell Differentiation , Physiology , Cell Lineage , Physiology , Homeostasis , Physiology , Humans , Nervous System , Neurons , Physiology
11.
Article in English | WPRIM | ID: wpr-764063

ABSTRACT

BACKGROUND AND OBJECTIVES: Genomic imprinting modulates growth and development in mammals and is associated with genetic disorders. Although uniparental embryonic stem cells have been used to study genomic imprinting, there is an ethical issue associated with the destruction of human embryos. In this study, to investigate the genomic imprinting status in human neurodevelopment, we used human uniparental induced pluripotent stem cells (iPSCs) that possessed only maternal alleles and differentiated into neural cell lineages. METHODS: Human somatic iPSCs (hSiPSCs) and human parthenogenetic iPSCs (hPgiPSCs) were differentiated into neural stem cells (NSCs) and named hSi-NSCs and hPgi-NSCs respectively. DNA methylation and gene expression of imprinted genes related neurodevelopment was analyzed during reprogramming and neural lineage differentiation. RESULTS: The DNA methylation and expression of imprinted genes were altered or maintained after differentiation into NSCs. The imprinting status in NSCs were maintained after terminal differentiation into neurons and astrocytes. In contrast, gene expression was differentially presented in a cell type-specific manner. CONCLUSIONS: This study suggests that genomic imprinting should be determined in each neural cell type because the genomic imprinting status can differ in a cell type-specific manner. In addition, the in vitro model established in this study would be useful for verifying the epigenetic alteration of imprinted genes which can be differentially changed during neurodevelopment in human and for screening novel imprinted genes related to neurodevelopment. Moreover, the confirmed genomic imprinting status could be used to find out an abnormal genomic imprinting status of imprinted genes related with neurogenetic disorders according to uniparental genotypes.


Subject(s)
Alleles , Astrocytes , Cell Lineage , DNA Methylation , Embryonic Stem Cells , Embryonic Structures , Epigenomics , Ethics , Gene Expression , Genomic Imprinting , Genotype , Growth and Development , Humans , In Vitro Techniques , Induced Pluripotent Stem Cells , Mammals , Mass Screening , Neural Stem Cells , Neurons
12.
Article in English | WPRIM | ID: wpr-761894

ABSTRACT

BACKGROUND: Lonocyte-derived multipotential cells (MOMCs) include progenitors capable of differentiation into multiple cell lineages and thus represent an ideal autologous transplantable cell source for regenerative medicine. In this study, we cultured MOMCs, generated from mononuclear cells of peripheral blood, on the surface of nanocomposite thin films. METHODS: For this purpose, nanocomposite Poly(e-caprolactone) (PCL)-based thin films containing either 2.5 wt% silica nanotubes (SiO2ntbs) or strontium hydroxyapatite nanorods (SrHAnrds), were prepared using the spin-coating method. The induced differentiation capacity of MOMCs, towards bone and endothelium, was estimated using flow cytometry, real-time polymerase chain reaction, scanning electron microscopy and fluorescence microscopy after cells' genetic modification using the Sleeping Beauty Transposon System aiming their observation onto the scaffolds. Moreover, Wharton's Jelly Mesenchymal Stromal Cells were cultivated as a control cell line, while Human Umbilical Vein Endothelial Cells were used to strengthen and accelerate the differentiation procedure in semi-permeable culture systems. Finally, the cytotoxicity of the studied materials was checked with MTT assay. RESULTS: The highest differentiation capacity of MOMCs was observed on PCL/SiO2ntbs 2.5 wt% nanocomposite film, as they progressively lost their native markers and gained endothelial lineage, in both protein and transcriptional level. In addition, the presence of SrHAnrds in the PCL matrix triggered processes related to osteoblast bone formation. CONCLUSION: To conclude, the differentiation of MOMCs was selectively guided by incorporating SiO2ntbs or SrHAnrds into a polymeric matrix, for the first time.


Subject(s)
Autografts , Beauty , Cell Line , Cell Lineage , Durapatite , Endothelium , Flow Cytometry , Human Umbilical Vein Endothelial Cells , Mesenchymal Stem Cells , Methods , Microscopy, Electron, Scanning , Microscopy, Fluorescence , Nanocomposites , Nanotubes , Osteoblasts , Osteogenesis , Polymers , Real-Time Polymerase Chain Reaction , Regenerative Medicine , Silicon Dioxide , Strontium , Wharton Jelly
14.
Article in English | WPRIM | ID: wpr-718522

ABSTRACT

Stem cells are undifferentiated cells capable of self-renewal and differentiation into various cell lineages. Stem cells are responsible for the development of organs and regeneration of damaged tissues. The highly regenerative nature of the human endometrium during reproductive age suggests that stem cells play a critical role in endometrial physiology. Bone marrow-derived cells migrate to the uterus and participate in the healing and restoration of functionally or structurally damaged endometrium. This review summarizes recent research into the potential therapeutic effects of bone marrow-derived stem cells in conditions involving endometrial impairment.


Subject(s)
Bone Marrow , Cell Lineage , Endometrium , Female , Humans , Physiology , Regeneration , Stem Cells , Therapeutic Uses , Uterus
15.
Article in English | WPRIM | ID: wpr-739490

ABSTRACT

The small GTP-binding protein Rab25 is associated with tumor formation and progression. However, recent studies have shown discordant effects of Rab25 on cancer cell progression depending on cell lineage. In the present study, we elucidate the underlying mechanisms by which Rab25 induces cellular invasion. We demonstrate that Rab25 increases β1 integrin levels and subsequent activation of EGFR and upregulation of VEGF-A expression, leading to increased Snail expression, epithelial-to-mesenchymal transition and cancer cell invasiveness. Strikingly, we identify that Snail mediates Rab25-induced cancer cell invasiveness through fascin expression and that ectopic expression of Rab25 aggravates metastasis of ovarian cancer cells to the lung. We thus demonstrate a novel role of a β1 integrin/EGFR/VEGF-A/Snail signaling cascade in Rab25-induced cancer cell aggressiveness through induction of fascin expression, thus providing novel biomarkers and potential therapeutic targets for Rab25-expressing cancer cells.


Subject(s)
Biomarkers , Cell Lineage , Ectopic Gene Expression , GTP-Binding Proteins , Lung , Neoplasm Metastasis , Ovarian Neoplasms , Snails , Up-Regulation , Vascular Endothelial Growth Factor A
16.
Article in English | WPRIM | ID: wpr-107499

ABSTRACT

Bone marrow aspirates concentrate (BMAC) transplantation is a well-known technique for cartilage regeneration with good clinical outcomes for symptoms in patients with osteoarthritis (OA). Magnetic resonance imaging (MRI) has an important role in evaluating the degree of cartilage repair in cartilage regeneration therapy instead of a second assessment via an arthroscopy. We experienced a case of hypertrophic regeneration of the cartilage and a presumed simultaneous regeneration of the posterior horn of the lateral meniscus after BMAC transplantation for a cartilage defect at the lateral tibial and femoral condyle. This report provides the details of a case of an unusual treatment response after a BMAC transplant. This report is the first of its kind to demonstrate a MR image that displays the simultaneous regeneration of the cartilage and meniscus with a differentiation ability of the mesenchymal stem cell to the desired cell lineage.


Subject(s)
Animals , Arthroscopy , Bone Marrow , Cartilage , Cell Lineage , Horns , Humans , Hypertrophy , Magnetic Resonance Imaging , Menisci, Tibial , Mesenchymal Stem Cells , Osteoarthritis , Regeneration
17.
Article in English | WPRIM | ID: wpr-655776

ABSTRACT

Differentiation of mesenchymal stem cells (MSC) into a variety of cell lineages such as adipocytes, osteocytes, and chondrocytes is often accompanied up-regulation of autophagy. In our study, we demonstrated that the expression of autophagy-associated proteins (p-Beclin 1, LC3A, LC3B, p-AMPK, p-mTOR and ATG3, ATG7, and ATG12-5) over a period of time was hardly distinguishable from control tonsil-derived MSC (TMSC). Despite the unnoticeable difference in autophagy activation between differentiated TMSC (dTMSC) and the control (cTMSC), we reported significant changes in intracellular compositions in differentiated TMSC into functional parathyroid-like cells secreting parathyroid hormone (PTH). By using transmission electron microscopy (TEM), we observed accumulation of multivesicular bodies (MVB) comprising small, degraded compartments densely accumulated as dark granular or amorphous clumps, multilamellar bodies and lipid droplets in dTMSC. However, no such structures were found in cTMSC. These results suggest that differentiation of TMSC into parathyroid-like cells producing PTH hormone is hardly dependent on autophagy activation in the beginning of our conditions. Furthermore, our results of intracellular remodeling and accumulated endo-lysosomal storage bodies in the later stages of TMSC differentiation present a possible role of the structures in PTH secretion.


Subject(s)
Adipocytes , Autophagy , Cell Lineage , Chondrocytes , Lipid Droplets , Lysosomes , Mesenchymal Stem Cells , Microscopy, Electron, Transmission , Multivesicular Bodies , Osteocytes , Parathyroid Hormone , Up-Regulation
18.
Article in English | WPRIM | ID: wpr-649863

ABSTRACT

Mesenchymal stem cells (MSCs) can be obtained from a variety of human tissues. Placenta has become an attractive stem cell source for potential applications in regenerative medicine and tissue engineering. The aim of this study was to localize and characterize MSCs within human chorionic membranes (hCMSCs). For this purpose, immunofluorescence labeling with CD105 and CD90 were used to determine the distribution of MSCs in chorionic membranes tissue. A medium supplemented with a synthetic serum and various concentrations of neurotrophic factors and cytokines was used to induce hCMSCs to neural cells. The results showed that the CD90 positive cells were scattered in the chorionic membranes tissue, and the CD105 positive cells were mostly located around the small blood vessels. hCMSCs expressed typical mesenchymal markers (CD73, CD90, CD105, CD44 and CD166) but not hematopoietic markers (CD45, CD34) and HLA-DR. hCMSCs differentiated into adipocytes, osteocytes, chondrocytes, and neuronal cells, as revealed by morphological changes, cell staining, immunofluorescence analyses, and RT-PCR showing the tissue-specific gene presence for differentiated cell lineages after the treatment with induce medium. Human chorionic membranes may be the source of MSCs for treatment of nervous system injury.


Subject(s)
Adipocytes , Blood Vessels , Cell Lineage , Chondrocytes , Chorion , Cytokines , Fluorescent Antibody Technique , HLA-DR Antigens , Humans , Membranes , Mesenchymal Stem Cells , Nerve Growth Factors , Neurons , Osteocytes , Placenta , Regenerative Medicine , Stem Cells , Tissue Engineering , Trauma, Nervous System
19.
Article in English | WPRIM | ID: wpr-646589

ABSTRACT

Human breast milk stem cells (hBSCs) contain a population of cells with the ability to differentiate into various cell lineages for cell therapy applications. The current study examined the differentiation potential of hBSCs into hepatocytes- like cells. The cells were isolated from the breast milk and were treated with hepatogenic medium containing hepatocyte growth factor, insulin-like growth factor and dexamethasone for 7 days subsequently; Oncostatin M was added to the culture media. RT-PCR and immunocytochemistry were performed to detect the hepatogenic markers. The glycogen storage and the ability of the cells to absorb and release indocynanin green were also tested. The data showed that most of the differentiated cells formed cell aggregates after the 30th day, with more cells accumulated to form spheroids. RT-PCR revealed the expression of the hepatic nuclear factor, albumin, cytokeratin 18 and 19, cytochrome P2B6, glucose-6-phospahtase and claudin. The functional assays also showed glycogen storage and omission of indicynine green. Our study demonstrated hBSCs are novel population that can differentiate into hepatocyte-like cells.


Subject(s)
Breast , Cell Culture Techniques , Cell Lineage , Cell- and Tissue-Based Therapy , Culture Media , Cytochromes , Dexamethasone , Glycogen , Hepatocyte Growth Factor , Hepatocytes , Humans , Immunohistochemistry , Keratin-18 , Mesenchymal Stem Cells , Milk, Human , Oncostatin M , Stem Cells
20.
Article in English | WPRIM | ID: wpr-57418

ABSTRACT

Mesenchymal stem cells (MSCs) isolated from various tissues have been well characterized for therapeutic application to clinical diseases. However, in contrast to MSCs from other animal species, the characteristics of feline MSCs have not been fully documented. In this study, we conducted extensive characterization of feline adipose tissue-derived MSCs (fAD-MSCs). Study fAD-MSCs were individually isolated from the intra-abdominal adipose tissues of six felines. The expression levels of cell surface markers and pluripotent markers were evaluated. Next, proliferation capacity was analyzed by performing cumulative population doubling level (CPDL) and doubling time (DT) calculation assays. Differentiation potentials of fAD-MSCs into mesodermal cell lineages were analyzed by examining specific staining and molecular markers. All fAD-MSCs positively expressed cell surface markers such as CD29, CD44, CD90, CD105, CD166, and MHC-I, while CD14, CD34, CD45, and CD73 were negatively expressed. The CPDL of the fAD-MSCs was maintained until passage 5 to 6 (P5 to P6), whereas DT increased after P3 to P4. Also, stem cell-specific pluripotent markers (Oct3/4, Nanog, and SSEA-4) were detected. Importantly, all fAD-MSCs demonstrated mesodermal differentiation capacity. These results suggest that fully characterized fAD-MSCs could be beneficial when considering the use of these cells in feline disease research.


Subject(s)
Animals , Cat Diseases , Cats , Cell Lineage , Mesenchymal Stem Cells , Mesoderm
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