WorldWideScience

Sample records for blood haematopoietic progenitors

  1. Radiosensitivity of human haematopoietic stem/progenitor cells

    International Nuclear Information System (INIS)

    The haematopoietic system is regenerative tissue with a high proliferative potential; therefore, haematopoietic stem cells (HSCs) are sensitive to extracellular oxidative stress caused by radiation and chemotherapeutic agents. An understanding of this issue can help predict haematopoietic recovery from radiation exposure as well as the extent of radiation damage to the haematopoietic system. In the present study, the radiosensitivity of human lineage-committed myeloid haematopoietic stem/progenitor cells (HSPCs), including colony-forming unit–granulocyte macrophage, burst-forming unit–erythroid and colony-forming unit–granulocyte–erythroid–macrophage–megakaryocyte cells, which are contained in adult individual peripheral blood (PB) and fetus/neonate placental/umbilical cord blood (CB), were studied. The PB of 59 healthy individual blood donors and the CB of 42 neonates were investigated in the present study. HSPCs prepared from PB and CB were exposed to 0.5 or 2 Gy x-irradiation. The results showed that large individual differences exist in the surviving fraction of cells. In the case of adult PB, a statistically significant negative correlation was observed between the surviving fraction observed at a dose of 0.5 Gy and the age of the blood donors; however, none of these correlations were observed after 2 Gy x-irradiation. In addition, seasonal and gender variation were observed in the surviving fraction of CB HSPCs. The present results suggest that there are large individual differences in the surviving fraction of HSPCs contained in both adult PB and fetus/neonate CB. In addition, some factors, including the gender, age and season of birth, affect the radiosensitivity of HSPCs, especially with a relatively low-dose exposure. (paper)

  2. Maturation of blood vessels by haematopoietic stem cells and progenitor cells: involvement of apelin/APJ and angiopoietin/Tie2 interactions in vessel caliber size regulation.

    Science.gov (United States)

    Takakura, Nobuyuki; Kidoya, Hiroyasu

    2009-06-01

    Apelin is a recently-isolated bioactive peptide from bovine gastric extract. The gene encodes a protein of 77 amino acids, which can generate two active polypeptides, long (42-77) and short (65-77). Both peptides ligate and activate APJ, a G protein-coupled receptor expressed in the cardiovascular and central nervous systems. Although an essential role for the apelin/APJ system in blood vessel formation has been reported in Xenopus, its precise function in mammals is unclear. Blood vessel tube formation is accomplished by two main mechanisms: 1) single cell hollowing, in which a lumen forms within the cytoplasm of a single endothelial cell (EC), and 2) cord hollowing in which a luminal cavity is created de novo between ECs in a thin cylindrical cord. Molecular control of either single cell or cord hollowing has not been precisely determined. Angiopoietin-1 (Ang1) has been reported to induce enlargement of blood vessels. Apelin is produced from ECs upon activation of Tie2, a cognate receptor of Ang1, expressed on ECs. It has been suggested that apelin induces cord hollowing by promoting proliferation and aggregation/assembly of ECs. During angiogenesis, haematopoietic stem cells (HSCs) and progenitor cells (HPCs) are frequently observed in the perivascular region. They produce Ang1 and induce migration of ECs, resulting in a fine vascular network. Moreover, HSCs/HPCs can induce apelin production from ECs. Therefore, this review article posits that HSCs/HPCs regulate caliber size of blood vessels via apelin/APJ and Angiopoietin/Tie2 interactions.

  3. Effects of extracellular matrix proteins on the growth of haematopoietic progenitor cells.

    Science.gov (United States)

    Celebi, Betül; Mantovani, Diego; Pineault, Nicolas

    2011-10-01

    Umbilical cord blood (UCB) transplantation and haematological recovery are currently limited by the amount of haematopoietic progenitor cells (HPCs) present in each unit. HPCs and haematopoietic stem cells (HSCs) normally interact with cells and extracellular matrix (ECM) proteins present within the endosteal and vascular niches. Hence, we investigated whether coating of culture surfaces with ECM proteins normally present in the marrow microenvironment could benefit the ex vivo expansion of HPCs. Towards this, collagen types I and IV (COL I and IV), laminin (LN) and fibronectin (FN) were tested individually or as component of two ECM-mix complexes. Individually, ECM proteins had both common and unique properties on the growth and differentiation of UCB CD34+ cells; some ECM proteins favoured the differentiation of some lineages over that of others (e.g. FN for erythroids), some the expansion of HPCs (e.g. LN and megakaryocyte (MK) progenitor) while others had less effects. Next, two ECM-mix complexes were tested; the first one contained all four ECM proteins (4ECMp), while the second 'basement membrane-like structure' was without COL I (3ECMp). Removal of COL I led to strong reductions in cell growth and HPCs expansion. Interestingly, the 4ECMp-mix complex reproducibly increased CD34+ (1.3-fold) and CD41+ (1.2-fold) cell expansions at day 6 (P < 0.05) versus control, and induced greater myeloid progenitor expansion (P < 0.05) than 3ECMp. In conclusion, these results suggest that optimization of BM ECM protein complexes could provide a better environment for the ex vivo expansion of haematopoietic progenitors than individual ECM protein.

  4. Effects of extracellular matrix proteins on the growth of haematopoietic progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Celebi, Betuel; Pineault, Nicolas [Hema-Quebec, Research and Development Department, Quebec City, G1V 5C3, PQ (Canada); Mantovani, Diego, E-mail: nicolas.pineault@hema-quebec.qc.ca [Laboratory for Biomaterials and Bioengineering, Department of Materials Engineering and University Hospital Research Center, Laval University, Quebec City, G1V 0A6, PQ (Canada)

    2011-10-15

    Umbilical cord blood (UCB) transplantation and haematological recovery are currently limited by the amount of haematopoietic progenitor cells (HPCs) present in each unit. HPCs and haematopoietic stem cells (HSCs) normally interact with cells and extracellular matrix (ECM) proteins present within the endosteal and vascular niches. Hence, we investigated whether coating of culture surfaces with ECM proteins normally present in the marrow microenvironment could benefit the ex vivo expansion of HPCs. Towards this, collagen types I and IV (COL I and IV), laminin (LN) and fibronectin (FN) were tested individually or as component of two ECM-mix complexes. Individually, ECM proteins had both common and unique properties on the growth and differentiation of UCB CD34+ cells; some ECM proteins favoured the differentiation of some lineages over that of others (e.g. FN for erythroids), some the expansion of HPCs (e.g. LN and megakaryocyte (MK) progenitor) while others had less effects. Next, two ECM-mix complexes were tested; the first one contained all four ECM proteins (4ECMp), while the second 'basement membrane-like structure' was without COL I (3ECMp). Removal of COL I led to strong reductions in cell growth and HPCs expansion. Interestingly, the 4ECMp-mix complex reproducibly increased CD34+ (1.3-fold) and CD41+ (1.2-fold) cell expansions at day 6 (P < 0.05) versus control, and induced greater myeloid progenitor expansion (P < 0.05) than 3ECMp. In conclusion, these results suggest that optimization of BM ECM protein complexes could provide a better environment for the ex vivo expansion of haematopoietic progenitors than individual ECM protein.

  5. BSHI Guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation.

    Science.gov (United States)

    Little, A-M; Green, A; Harvey, J; Hemmatpour, S; Latham, K; Marsh, S G E; Poulton, K; Sage, D

    2016-10-01

    A review of the British Society for Histocompatibility and Immunogenetics (BSHI) "Guideline for selection and HLA matching of related, adult unrelated donors and umbilical cord units for haematopoietic progenitor cell transplantation" was undertaken by a BSHI appointed writing committee. Literature searches were performed, and the data extracted were presented as recommendations according to the GRADE nomenclature. PMID:27503599

  6. Indium-111 oxine labelling affects the cellular integrity of haematopoietic progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Nowak, Bernd; Reinartz, Patrick; Schaefer, Wolfgang M.; Buell, Ulrich [University Hospital, RWTH Aachen University, Department of Nuclear Medicine, Aachen (Germany); Weber, Christian; Schober, Andreas; Zeiffer, Ute; Liehn, Elisa A.; Hundelshausen, Philipp von [University Hospital, RWTH Aachen University, Department of Molecular Cardiovascular Research, Aachen (Germany)

    2007-05-15

    Cell-based therapy by transplantation of progenitor cells has emerged as a promising development for organ repair, but non-invasive imaging approaches are required to monitor the fate of transplanted cells. Radioactive labelling with {sup 111}In-oxine has been used in preclinical trials. This study aimed to validate {sup 111}In-oxine labelling and subsequent in vivo and ex vivo detection of haematopoietic progenitor cells. Murine haematopoietic progenitor cells (10{sup 6}, FDCPmix) were labelled with 0.1 MBq (low dose) or 1.0 MBq (high dose) {sup 111}In-oxine and compared with unlabelled controls. Cellular retention of {sup 111}In, viability and proliferation were determined up to 48 h after labelling. Labelled cells were injected into the cavity of the left or right cardiac ventricle in mice. Scintigraphic images were acquired 24 h later. Organ samples were harvested to determine the tissue-specific activity. Labelling efficiency was 75 {+-} 14%. Cellular retention of incorporated {sup 111}In after 48 h was 18 {+-} 4%. Percentage viability after 48 h was 90 {+-} 1% (control), 58 {+-} 7% (low dose) and 48 {+-} 8% (high dose) (p<0.0001). Numbers of viable cells after 48 h (normalised to 0 h) were 249 {+-} 51% (control), 42 {+-} 8% (low dose) and 32 {+-} 5% (high dose) (p<0.0001). Cells accumulated in the spleen (86.6 {+-} 27.0% ID/g), bone marrow (59.1 {+-} 16.1% ID/g) and liver (30.3 {+-} 9.5% ID/g) after left ventricular injection, whereas most of the cells were detected in the lungs (42.4 {+-} 21.8% ID/g) after right ventricular injection. Radiolabelling of haematopoietic progenitor cells with {sup 111}In-oxine is feasible, with high labelling efficiency but restricted stability. The integrity of labelled cells is significantly affected, with substantially reduced viability and proliferation and limited migration after systemic transfusion. (orig.)

  7. Xpg limits the expansion of haematopoietic stem and progenitor cells after ionising radiation.

    Science.gov (United States)

    Avila, Alush I; Illing, Anett; Becker, Friedrich; Maerz, Lars D; Morita, Yohei; Philipp, Melanie; Burkhalter, Martin D

    2016-07-27

    Reduced capacity of genome maintenance represents a problem for any organism, potentially causing premature death, carcinogenesis, or accelerated ageing. Strikingly though, loss of certain genome stability factors can be beneficial, especially for the maintenance of tissue stem cells of the intestine and the haematopoietic system. We therefore screened for genome stability factors negatively impacting maintenance of haematopoietic stem cells (HSC) in the context of ionising radiation (IR). We found that in vivo knock down of Xeroderma pigmentosum, complementation group G (Xpg) causes elevation of HSC numbers after IR treatment, while numbers of haematopoietic progenitors are elevated to a lesser extent. IR rapidly induces Xpg both on mRNA and on protein level. Prevention of this induction does not influence activation of the checkpoint cascade, yet attenuates late checkpoint steps such as induction of p21 and Noxa. This causes a leaky cell cycle arrest and lower levels of apoptosis, both contributing to increased colony formation and transformation rates. Xpg thus helps to adequately induce DNA damage responses after IR, thereby keeping the expansion of damaged cells under control. This represents a new function of Xpg in the response to IR, in addition to its well-characterized role in nucleotide excision repair. PMID:27137888

  8. Absence of a relationship between immunophenotypic and colony enumeration analysis of endothelial progenitor cells in clinical haematopoietic cell sources

    Directory of Open Access Journals (Sweden)

    Turner Marc L

    2007-07-01

    Full Text Available Abstract Background The discovery of adult endothelial progenitor cells (EPC offers potential for vascular regenerative therapies. The expression of CD34 and VEGFR2 by EPC indicates a close relationship with haematopoietic progenitor cells (HPC, and HPC-rich sources have been used to treat cardiac and limb ischaemias with apparent clinical benefit. However, the laboratory characterisation of the vasculogenic capability of potential or actual therapeutic cell autograft sources is uncertain since the description of EPC remains elusive. Various definitions of EPC based on phenotype and more recently on colony formation (CFU-EPC have been proposed. Methods We determined EPC as defined by proposed phenotype definitions (flow cytometry and by CFU-EPC in HPC-rich sources: bone marrow (BM; cord blood (CB; and G-CSF-mobilised peripheral blood (mPB, and in HPC-poor normal peripheral blood (nPB. Results As expected, the highest numbers of cells expressing the HPC markers CD34 or CD133 were found in mPB and least in nPB. The proportions of CD34+ cells co-expressing CD133 is of the order mPB>CB>BM≈nPB. CD34+ cells co-expressing VEGFR2 were also most frequent in mPB. In contrast, CFU-EPC were virtually absent in mPB and were most readily detected in nPB, the source lowest in HPC. Conclusion HPC sources differ in their content of putative EPC. Normal peripheral blood, poor in HPC and in HPC-related phenotypically defined EPC, is the richest source of CFU-EPC, suggesting no direct relationship between the proposed EPC immunophenotypes and CFU-EPC potential. It is not apparent whether either of these EPC measurements, or any, is an appropriate indicator of the therapeutic vasculogenic potential of autologous HSC sources.

  9. Polyurethane scaffolds seeded with CD34+ cells maintain early stem cells whilst also facilitating prolonged egress of haematopoietic progenitors

    Science.gov (United States)

    Severn, Charlotte E.; Macedo, Hugo; Eagle, Mark J.; Rooney, Paul; Mantalaris, Athanasios; Toye, Ashley M.

    2016-01-01

    We describe a 3D erythroid culture system that utilises a porous polyurethane (PU) scaffold to mimic the compartmentalisation found in the bone marrow. PU scaffolds seeded with peripheral blood CD34+ cells exhibit a remarkable reproducibility of egress, with an increased output when directly compared to human bone scaffolds over 28 days. Immunofluorescence demonstrated the persistence of CD34+ cells within the scaffolds for the entirety of the culture. To characterise scaffold outputs, we designed a flow cytometry panel that utilises surface marker expression observed in standard 2D erythroid and megakaryocyte cultures. This showed that the egress population is comprised of haematopoietic progenitor cells (CD36+GPA−/low). Control cultures conducted in parallel but in the absence of a scaffold were also generally maintained for the longevity of the culture albeit with a higher level of cell death. The harvested scaffold egress can also be expanded and differentiated to the reticulocyte stage. In summary, PU scaffolds can behave as a subtractive compartmentalised culture system retaining and allowing maintenance of the seeded “CD34+ cell” population despite this population decreasing in amount as the culture progresses, whilst also facilitating egress of increasingly differentiated cells. PMID:27573994

  10. Polyurethane scaffolds seeded with CD34(+) cells maintain early stem cells whilst also facilitating prolonged egress of haematopoietic progenitors.

    Science.gov (United States)

    Severn, Charlotte E; Macedo, Hugo; Eagle, Mark J; Rooney, Paul; Mantalaris, Athanasios; Toye, Ashley M

    2016-01-01

    We describe a 3D erythroid culture system that utilises a porous polyurethane (PU) scaffold to mimic the compartmentalisation found in the bone marrow. PU scaffolds seeded with peripheral blood CD34(+) cells exhibit a remarkable reproducibility of egress, with an increased output when directly compared to human bone scaffolds over 28 days. Immunofluorescence demonstrated the persistence of CD34(+) cells within the scaffolds for the entirety of the culture. To characterise scaffold outputs, we designed a flow cytometry panel that utilises surface marker expression observed in standard 2D erythroid and megakaryocyte cultures. This showed that the egress population is comprised of haematopoietic progenitor cells (CD36(+)GPA(-/low)). Control cultures conducted in parallel but in the absence of a scaffold were also generally maintained for the longevity of the culture albeit with a higher level of cell death. The harvested scaffold egress can also be expanded and differentiated to the reticulocyte stage. In summary, PU scaffolds can behave as a subtractive compartmentalised culture system retaining and allowing maintenance of the seeded "CD34(+) cell" population despite this population decreasing in amount as the culture progresses, whilst also facilitating egress of increasingly differentiated cells. PMID:27573994

  11. Expression of Fbxo7 in haematopoietic progenitor cells cooperates with p53 loss to promote lymphomagenesis.

    Directory of Open Access Journals (Sweden)

    Mikhail Lomonosov

    Full Text Available Fbxo7 is an unusual F box protein that augments D-type cyclin complex formation with Cdk6, but not Cdk4 or Cdk2, and its over-expression has been demonstrated to transform immortalised fibroblasts in a Cdk6-dependent manner. Here we present new evidence in vitro and in vivo on the oncogenic potential of this regulatory protein in primary haematopoietic stem and progenitor cells (HSPCs. Increasing Fbxo7 expression in HSPCs suppressed their colony forming ability in vitro, specifically decreasing CD11b (Mac1 expression, and these effects were dependent on an intact p53 pathway. Furthermore, increased Fbxo7 levels enhanced the proliferative capacity of p53 null HSPCs when they were grown in reduced concentrations of stem cell factor. Finally, irradiated mice reconstituted with p53 null, but not wild-type, HSPCs expressing Fbxo7 showed a statistically significant increase in the incidence of T cell lymphoma in vivo. These data argue that Fbxo7 negatively regulates the proliferation and differentiation of HSPCs in a p53-dependent manner, and that in the absence of p53, Fbxo7 expression can promote T cell lymphomagenesis.

  12. Targeting the delivery of systemically administered haematopoietic stem/progenitor cells to the inflamed colon using hydrogen peroxide and platelet microparticle pre-treatment strategies

    OpenAIRE

    Adrian Yemm; David Adams; Neena Kalia

    2015-01-01

    Haematopoietic stem and progenitor cell (HSC) therapy may be promising for the treatment of inflammatory bowel disorders (IBDs). However, clinical success remains poor, partly explained by limited HSC recruitment following systemic delivery. The mechanisms governing HSC adhesion within inflamed colon, and whether this event can be enhanced, are not known. An immortalised HSC-like line (HPC7) was pre-treated with hydrogen peroxide (H2O2), activated platelet releasate enriched supernatant (PES)...

  13. Haemopoietic progenitor cells in human peripheral blood

    International Nuclear Information System (INIS)

    The purpose of the investigation reported is to purify haemopoietic progenitor cells from human peripheral blood using density gradient centrifugation in order to isolate a progenitor cell fraction without immunocompetent cells. The purification technique of peripheral blood flow colony forming unit culture (CFU-c) by means of density gradient centrifugation and a combined depletion of various rosettes is described. The results of several 'in vitro' characteristics of purified CFU-c suspensions and of the plasma clot diffusion chamber culture technique are presented. Irradiation studies revealed that for both human bone marrow and peripheral blood the CFU-c were less radioresistant than clusters. Elimination of monocytes (and granulocytes) from the test suspensions induced an alteration in radiosensitivity pararmeters. The results obtained with the different techniques are described by analysing peripheral progenitor cell activity in myeloproliferative disorders. (Auth.)

  14. Short and long-term safety of lenograstim administration in healthy peripheral haematopoietic progenitor cell donors: a single centre experience.

    Science.gov (United States)

    Martino, M; Console, G; Dattola, A; Callea, I; Messina, G; Moscato, T; Massara, E; Irrera, G; Fedele, R; Gervasi, A; Bresolin, G; Iacopino, P

    2009-08-01

    Healthy donors (HDs) who were mobilized using lenograstim (LENO) and who were undergoing peripheral haematopoietic progenitor cell collection with apheresis (HPC-A) were enrolled in a surveillance protocol. In all, 184 HDs have been assessed with a median follow-up of 62 months (range 2-155). HDs received LENO at a median dose of 10 microg/kg (range 5-15). Bone pain was reported as the most frequent short-term adverse event (71.2%). Other commonly observed short-term symptoms included fatigue (19.0%), fever (5.4%), headache (27.7%), nausea (12.0%) and insomnia (22.3%). Spleen size increased in 4.3% of the donors. No vascular disorders or cardiac disease occurred. Long-term follow-up included monitoring of adverse events, neoplastic disease or other pathologies. Transit ischaemic attack occurred in one donor (39 months post-donation). One autoimmune event was reported at 28 months post-recombinant human granulocyte (rhG)-CSF (ankylosing spondylitis); one donor with a history of chronic obstructive pulmonary disease developed secondary polyglobulia (50 months post-rhG-CSF). One donor was diagnosed with lung cancer at 19 months post-donation. No haematological disease was observed. In conclusion, the short-term safety appears to be verified, whereas, although the study identified no increased risks of malignancy among HDs who received rhG-CSF, long-term safety requires more complete data sets, especially a longer follow-up and a larger number of HDs. PMID:19182833

  15. [Effectiveness of plerixafor in patients undergoing mobilization autologous haematopoietic progenitor cell].

    Science.gov (United States)

    Ruano Camps, R; Ortiz Pareja, M; Vidales Mancha, I; Muñoz Castillo, I M; Heiniger Mazo, A I

    2013-01-01

    Objetivo: Evaluar efectividad del tratamiento con plerixafor en pacientes sometidos a movilización para posterior autotrasplante de progenitores hematopoyéticos en nuestro hospital. Métodos: Estudio retrospectivo de todos los pacientes que hasta septiembre 2012, recibieron plerixafor en su esquema de movilización de progenitores hematopoyéticos a sangre periférica. Se revisaron las historias clínicas y los registros de dispensación de medicamentos de la consulta de pacientes externos. Las variables de efectividad utilizadas fueron: CD34/kg en producto de aféresis obtenidas, dosis y días recibidos de factor estimulante de colonias (G-CSF) y de plerixafor. Para cada paciente se comparó los resultados de efectividad del fármaco con los obtenidos para anteriores esquemas de movilización en los que no se utilizó plerixafor, en caso de tenerlos. Los datos se analizaron mediante IBM spss v19. Resultados: Un total de 24 pacientes recibieron plerixafor en nuestro hospital. Los diagnósticos se distribuyeron: 15 linfoma no Hodgkin , 6 pacientes con mieloma múltiple, 2 enfermedad de Hodgkin, y 1 coriocarcinoma diseminado. Los resultados de efectividad fueron: Movilización sin plerixafor (n = 18): 5 pacientes se movilizaron sólo con G-CSGF, 13 con G-CSF y quimioterapia. La dosis de G-CSF /día fue de 931,1 mcg (± 179,5), durante 9,5 días (± 4,7). El promedio de CD34/kg en producto obtenido fue de 0,2 células (± 0,5). Ningún paciente obtuvo producto suficiente (≥?2 x 106 células/kg) para el posterior autotrasplante. El 100 % de las movilizaciones fracasaron. Movilización con plerixafor (n = 24): 13 pacientes se movilizaron sólo con G-CSGF, 11 con G-CSF y quimioterapia. La dosis de G-CSF /día y de plerixafor promedio fue de 885,1 mcg (± 240,1) y 19,8 (± 4,4), respectivamente, administrados durante 8,9 (± 5,1) y 1,5 (± 0,6) días, respectivamente. El promedio de CD34/kg en producto obtenido fue de 2,3x106 células (±1,7) (p = 0,014, en relaci

  16. Functional Blood Progenitor Markers in Developing Human Liver Progenitors.

    Science.gov (United States)

    Goldman, Orit; Cohen, Idan; Gouon-Evans, Valerie

    2016-08-01

    In the early fetal liver, hematopoietic progenitors expand and mature together with hepatoblasts, the liver progenitors of hepatocytes and cholangiocytes. Previous analyses of human fetal livers indicated that both progenitors support each other's lineage maturation and curiously share some cell surface markers including CD34 and CD133. Using the human embryonic stem cell (hESC) system, we demonstrate that virtually all hESC-derived hepatoblast-like cells (Hep cells) transition through a progenitor stage expressing CD34 and CD133 as well as GATA2, an additional hematopoietic marker that has not previously been associated with human hepatoblast development. Dynamic expression patterns for CD34, CD133, and GATA2 in hepatoblasts were validated in human fetal livers collected from the first and second trimesters of gestation. Knockdown experiments demonstrate that each gene also functions to regulate hepatic fate mostly in a cell-autonomous fashion, revealing unprecedented roles of fetal hematopoietic progenitor markers in human liver progenitors. PMID:27509132

  17. A Hedgehog- and Antennapedia-dependent niche maintains Drosophila haematopoietic precursors

    OpenAIRE

    Mandal, Lolitika; Martinez-Agosto, Julian A.; Evans, Cory J.; Hartenstein, Volker; Banerjee, Utpal

    2007-01-01

    The Drosophila melanogaster lymph gland is a haematopoietic organ1–3 in which pluripotent blood cell progenitors proliferate and mature into differentiated haemocytes. Previous work4 has defined three domains, the medullary zone, the cortical zone and the posterior signalling centre (PSC), within the developing third-instar lymph gland. The medullary zone is populated by a core of undifferentiated, slowly cycling progenitor cells, whereas mature haemocytes comprising plasmatocytes, crystal ce...

  18. ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression

    Science.gov (United States)

    Aryal, Binod; Rotllan, Noemi; Araldi, Elisa; Ramírez, Cristina M.; He, Shun; Chousterman, Benjamin G.; Fenn, Ashley M.; Wanschel, Amarylis; Madrigal-Matute, Julio; Warrier, Nikhil; Martín-Ventura, Jose L.; Swirski, Filip K.; Suárez, Yajaira; Fernández-Hernando, Carlos

    2016-07-01

    Lipid accumulation in macrophages has profound effects on macrophage gene expression and contributes to the development of atherosclerosis. Here, we report that angiopoietin-like protein 4 (ANGPTL4) is the most highly upregulated gene in foamy macrophages and it's absence in haematopoietic cells results in larger atherosclerotic plaques, characterized by bigger necrotic core areas and increased macrophage apoptosis. Furthermore, hyperlipidemic mice deficient in haematopoietic ANGPTL4 have higher blood leukocyte counts, which is associated with an increase in the common myeloid progenitor (CMP) population. ANGPTL4-deficient CMPs have higher lipid raft content, are more proliferative and less apoptotic compared with the wild-type (WT) CMPs. Finally, we observe that ANGPTL4 deficiency in macrophages promotes foam cell formation by enhancing CD36 expression and reducing ABCA1 localization in the cell surface. Altogether, these findings demonstrate that haematopoietic ANGPTL4 deficiency increases atherogenesis through regulating myeloid progenitor cell expansion and differentiation, foam cell formation and vascular inflammation.

  19. Cord blood-circulating endothelial progenitors for treatment of vascular diseases.

    Science.gov (United States)

    Lavergne, M; Vanneaux, V; Delmau, C; Gluckman, E; Rodde-Astier, I; Larghero, J; Uzan, G

    2011-04-01

    Adult peripheral blood (PB) endothelial progenitor cells (EPC) are produced in the bone marrow and are able to integrate vascular structures in sites of neoangiogenesis. EPCs thus represent a potential therapeutic tool for ischaemic diseases. However, use of autologous EPCs in cell therapy is limited by their rarity in adult PB. Cord blood (CB) contains more EPCs than PB, and they are functional after expansion. They form primary colonies that give rise to secondary colonies, each yielding more than 10(7) cells after few passages. The number of endothelial cells obtained from one unit of CB is compatible with potential clinical application. EPC colonies can be securely produced, expanded and cryopreserved in close culture devices and endothelial cells produced in these conditions are functional as shown in different in vitro and in vivo assays. As CB EPC-derived endothelial cells would be allogeneic to patients, it would be of interest to prepare them from ready-existing CB banks. We show that not all frozen CB units from a CB bank are able to generate EPC colonies in culture, and when they do so, number of colonies is lower than that obtained with fresh CB units. However, endothelial cells derived from frozen CB have the same phenotypical and functional properties than those derived from fresh CB. This indicates that CB cryopreservation should be improved to preserve integrity of stem cells other than haematopoietic ones. Feasibility of using CB for clinical applications will be validated in porcine models of ischaemia.

  20. In vitro effect of amifostine on haematopoietic progenitors exposed to carboplatin and non-alkylating antineoplastic drugs: haematoprotection acts as a drug-specific progenitor rescue.

    OpenAIRE

    Pierelli, L.; Scambia, G; Fattorossi, A; Bonanno, G.; Battaglia, A; Perillo, A.; Menichella, G.; Panici, P. B.; Leone, G; Mancuso, S.

    1998-01-01

    We evaluated the protective ability of amifostine on peripheral blood mononuclear cell (PBMC)-derived colony-forming unit (CFU) and PB CD34+ cells which were previously exposed in vitro to etoposide, carboplatin, doxorubicin and taxotere. Amifostine pretreatment protected PBMC-derived CFU from the toxic effect of etoposide, carboplatin and taxotere. A significant detrimental effect was exerted by amifostine on the growth of doxorubicin-treated PBMC-derived CFU. Liquid cultures of PB CD34+ cel...

  1. Fludarabine and cytarabine combined chemotherapy followed by transfusion of donor blood stem cells for treating relapse of acute leukaemia after allogeneic haematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    YOU Yong; LI Qiu-bai; CHEN Zhi-chao; LI Wei-ming; XIA Ling-hui; ZHOU Hao; ZOU Ping

    2008-01-01

    Background Relapse remains an obstacle to successful allogeneic haematopoietic stem cell transplantation (alIo-HSCT) for patients with acute leukaemia and no standard treatment is available. We assessed fludarabine and cytarabine with transfusion of donor haematopoietic stem cell in treating the relapse of acute leukaemia after alIo-HSCT.Methods Seven patients, median age 34 years, with relapse of acute leukaemia after alIo-HSCT received combination chemotherapy of fludarabine with cytarabine for 5 days. Five patients suffered from acute myeloid leukaemia (2 refractory) and 2 refractory acute lymphoblastic leukaemia. After the transplantation, the median relapse time was 110 days (range,38-185 days). Two days after chemotherapy, 5 patients received infusion of donor's peripheral blood stem cells, mobilized by granulocyte colony stimulating factor. No prophylactic agents of graft versus host diseases were administered.Results Six patients achieved haematopoietic reconstitution. DNA sequence analysis at day 30 after treatment identified all as full donor chimera type. The median observation time was 189 days. After the treatment, the median time for neutrophilic granulocyte value ≥0.5x109/L and for platelet value >20x109/L were 13 days (range, 10-18 days) and 15 days (range, 11-24 days), respectively. Graft versus host disease occurred in 2 patients (acute) and 3 (chronic). Five patients suffered from pulmonary fungal infection (2 died), 3 haemorrhagic cystitis and 2 cytomegalovirus viraemia. The other patients died of leukaemia related deaths. Three patients with chronic graft versus host disease who had received donor peripheral blood stem cells reinfusion have survived for 375 days, 232 days and 195 days, respectively.Conclusions Fludarabine with cytarabine plus the donor haematopoietic stem cell should be considered as an effective therapeutic regimen for relapse of acute leukaemia after alIo-HSCT. The disease free state of patients may increase, thou.gh with

  2. Stem and progenitor cells in biostructure of blood vessel walls

    Directory of Open Access Journals (Sweden)

    Krzysztof Korta

    2013-09-01

    Full Text Available Development of vascular and hematopoietic systems during organogenesis occurs at the same time. During vasculogenesis, a small part of cells does not undergo complete differentiation but stays on this level, “anchored” in tissue structures described as stem cell niches. The presence of blood vessels within tissue stem cell niches is typical and led to identification of niches and ensures that they are functioning. The three-layer biostructure of vessel walls for artery and vein, tunica: intima, media and adventitia, for a long time was defined as a mechanical barrier between vessel light and the local tissue environment. Recent findings from vascular biology studies indicate that vessel walls are dynamic biostructures, which are equipped with stem and progenitor cells, described as vascular wall-resident stem cells/progenitor cells (VW-SC/PC. Distinct zones for vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described as “subendothelial or vasculogenic zones”. Recent evidence from in vitro and in vivo studies show that prenatal activity of stem and progenitor cells is not only limited to organogenesis but also exists in postnatal life, where it is responsible for vessel wall homeostasis, remodeling and regeneration. It is believed that VW-SC/PC could be engaged in progression of vascular disorders and development of neointima. We would like to summarize current knowledge about mesenchymal and progenitor stem cell phenotype with special attention to distribution and biological properties of VW-SC/PC in biostructures of intima, media and adventitia niches. It is postulated that in the near future, niches for VW-SC/PC could be a good source of stem and progenitor cells, especially in the context of vessel tissue bioengineering as a new alternative to traditional revascularization therapies.

  3. A Hedgehog- and Antennapedia-dependent niche maintains Drosophila haematopoietic precursors

    Science.gov (United States)

    Mandal, Lolitika; Martinez-Agosto, Julian A.; Evans, Cory J.; Hartenstein, Volker; Banerjee, Utpal

    2009-01-01

    The Drosophila melanogaster lymph gland is a haematopoietic organ1–3 in which pluripotent blood cell progenitors proliferate and mature into differentiated haemocytes. Previous work4 has defined three domains, the medullary zone, the cortical zone and the posterior signalling centre (PSC), within the developing third-instar lymph gland. The medullary zone is populated by a core of undifferentiated, slowly cycling progenitor cells, whereas mature haemocytes comprising plasmatocytes, crystal cells and lamellocytes are peripherally located in the cortical zone. The PSC comprises a third region that was first defined as a small group of cells expressing the Notch ligand Serrate5. Here we show that the PSC is specified early in the embryo by the homeotic gene Antennapedia (Antp) and expresses the signalling molecule Hedgehog. In the absence of the PSC or the Hedgehog signal, the precursor population of the medullary zone is lost because cells differentiate prematurely. We conclude that the PSC functions as a haematopoietic niche that is essential for the maintenance of blood cell precursors in Drosophila. Identification of this system allows the opportunity for genetic manipulation and direct in vivo imaging of a haematopoietic niche interacting with blood precursors. PMID:17361183

  4. Collection, processing and testing of bone, corneas, umbilical cord blood and haematopoietic stem cells by European Blood Alliance members

    DEFF Research Database (Denmark)

    Närhi, M; Natri, O; Desbois, I;

    2013-01-01

    A questionnaire study was carried out in collaboration with the European Blood Alliance (EBA) Tissues and Cells (T&C) working group. The aim was to assess the level of involvement and commonality of processes on the procurement, testing and storage of bone, corneas, umbilical cord blood (UCB...

  5. Red blood cell-incompatible allogeneic hematopoietic progenitor cell transplantation.

    Science.gov (United States)

    Rowley, S D; Donato, M L; Bhattacharyya, P

    2011-09-01

    Transplantation of hematopoietic progenitor cells from red cell-incompatible donors occurs in 30-50% of patients. Immediate and delayed hemolytic transfusion reactions are expected complications of red cell-disparate transplantation and both ABO and other red cell systems such as Kidd and rhesus can be involved. The immunohematological consequences of red cell-incompatible transplantation include delayed red blood cell recovery, pure red cell aplasia and delayed hemolysis from viable lymphocytes carried in the graft ('passenger lymphocytes'). The risks of these reactions, which may be abrupt in onset and fatal, are ameliorated by graft processing and proper blood component support. Red blood cell antigens are expressed on endothelial and epithelial tissues in the body and could serve to increase the risk of GvHD. Mouse models indicate that blood cell antigens may function as minor histocompatibility antigens affecting engraftment. Similar observations have been found in early studies of human transplantation for transfused recipients, although current conditioning and immunosuppressive regimens appear to overcome this affect. No deleterious effects from the use of red cell-incompatible hematopoietic grafts on transplant outcomes, such as granulocyte and platelet engraftments, the incidences of acute or chronic GvHD, relapse risk or OS, have been consistently demonstrated. Most studies, however, include limited number of patients, varying diagnoses and differing treatment regimens, complicating the detection of an effect of ABO-incompatible transplantation. Classification of patients by ABO phenotype ignoring the allelic differences of these antigens also may obscure the effect of red cell-incompatible transplantation on transplant outcomes. PMID:21897398

  6. Endothelial Progenitor Cells in Peripheral Blood of Cardiac Catheterization Personnel

    Directory of Open Access Journals (Sweden)

    Soheir Korraa1, Tawfik M.S.1, Mohamed Maher 2 and Amr Zaher

    2014-07-01

    Full Text Available Background: The aim of the present study was to evaluate the rejuvenation capacity among cardiac catheterization technicians occupationally exposed to ionizing radiation. Subjects and methods: The individual annual collective dose information was measured by thermoluminscent personal dosimeters (TLD for those technicians and found to be ranging between 2.16 and 8.44 mSv/y. Venous blood samples were obtained from 30 cardiac catheterization technicians exposed to X-ray during fluoroscopy procedures at the National Heart Institute in Embaba. The control group involved 25 persons not exposed to ionizing radiation and not working in hospitals in addition to 20 persons not exposed to ionizing radiation and working in hospitals. Blood samples were assayed for total and differential blood counts, micronucleus formation (FMN plasma stromal derived growth factor-1α (SDF-1 α and cell phenotype of circulating endothelial progenitor cells (EPCs, whose surface markers were identified as the CD34, CD133 and kinase domain receptors (KDR. Results: SDF-1α (2650± 270 vs. 2170 ± 430 pg/ml and FMN (19.9 ± 5.5 vs. 2.8 ± 1.4/1000 cells were significantly higher among cardiac catheterization staff compared to those of the controls respectively. Similarly, EPCs: CD34 (53 ± 3.9 vs. 48 ± 8.5/105 mononuclear cells, CD133 (62.4 ± 4.8 vs. 54.2 ± 10.6 /105 mononuclear cells KDR (52.7 ± 10.6 vs.43.5± 8.2 /105 mononuclear cells were also significantly higher among cardiac catheterization staff compared to the values of controls respectively. Smoking seemed to have a positive effect on the FMN and SDF-1 but had a negative effect on EPCs. It was found that among cardiac catheterization staff, the numbers of circulating progenitor cells had increased and accordingly there was an increased capacity for tissue repair. Conclusion: In conclusion, the present work shows that occupational exposure to radiation, well within permissible levels, leaves a genetic mark on the

  7. Bomapin is a redox-sensitive nuclear serpin that affects responsiveness of myeloid progenitor cells to growth environment

    OpenAIRE

    Larsson Göran; Tengel Tobias; Ramstedt Björn; Przygodzka Patrycja; Wilczynska Malgorzata

    2010-01-01

    Abstract Background Haematopoiesis is a process of formation of mature blood cells from hematopoietic progenitors in bone marrow. Haematopoietic progenitors are stimulated by growth factors and cytokines to proliferate and differentiate, and they die via apoptosis when these factors are depleted. An aberrant response to growth environment may lead to haematological disorders. Bomapin (serpinb10) is a hematopoietic- and myeloid leukaemia-specific protease inhibitor with unknown function. Resul...

  8. Promotion of haematopoietic activity in embryonic stem cells by the aorta-gonad-mesonephros microenvironment

    International Nuclear Information System (INIS)

    We investigated whether the in vitro differentiation of ES cells into haematopoietic progenitors could be enhanced by exposure to the aorta-gonadal-mesonephros (AGM) microenvironment that is involved in the generation of haematopoietic stem cells (HSC) during embryonic development. We established a co-culture system that combines the requirements for primary organ culture and differentiating ES cells and showed that exposure of differentiating ES cells to the primary AGM region results in a significant increase in the number of ES-derived haematopoietic progenitors. Co-culture of ES cells on the AM20-1B4 stromal cell line derived from the AGM region also increases haematopoietic activity. We conclude that factors promoting the haematopoietic activity of differentiating ES cells present in primary AGM explants are partially retained in the AM20.1B4 stromal cell line and that these factors are likely to be different to those required for adult HSC maintenance

  9. GFI1 proteins orchestrate the emergence of haematopoietic stem cells through recruitment of LSD1.

    Science.gov (United States)

    Thambyrajah, Roshana; Mazan, Milena; Patel, Rahima; Moignard, Victoria; Stefanska, Monika; Marinopoulou, Elli; Li, Yaoyong; Lancrin, Christophe; Clapes, Thomas; Möröy, Tarik; Robin, Catherine; Miller, Crispin; Cowley, Shaun; Göttgens, Berthold; Kouskoff, Valerie; Lacaud, Georges

    2016-01-01

    In vertebrates, the first haematopoietic stem cells (HSCs) with multi-lineage and long-term repopulating potential arise in the AGM (aorta-gonad-mesonephros) region. These HSCs are generated from a rare and transient subset of endothelial cells, called haemogenic endothelium (HE), through an endothelial-to-haematopoietic transition (EHT). Here, we establish the absolute requirement of the transcriptional repressors GFI1 and GFI1B (growth factor independence 1 and 1B) in this unique trans-differentiation process. We first demonstrate that Gfi1 expression specifically defines the rare population of HE that generates emerging HSCs. We further establish that in the absence of GFI1 proteins, HSCs and haematopoietic progenitor cells are not produced in the AGM, revealing the critical requirement for GFI1 proteins in intra-embryonic EHT. Finally, we demonstrate that GFI1 proteins recruit the chromatin-modifying protein LSD1, a member of the CoREST repressive complex, to epigenetically silence the endothelial program in HE and allow the emergence of blood cells. PMID:26619147

  10. Distinct bone marrow blood vessels differentially regulate haematopoiesis.

    Science.gov (United States)

    Itkin, Tomer; Gur-Cohen, Shiri; Spencer, Joel A; Schajnovitz, Amir; Ramasamy, Saravana K; Kusumbe, Anjali P; Ledergor, Guy; Jung, Yookyung; Milo, Idan; Poulos, Michael G; Kalinkovich, Alexander; Ludin, Aya; Kollet, Orit; Shakhar, Guy; Butler, Jason M; Rafii, Shahin; Adams, Ralf H; Scadden, David T; Lin, Charles P; Lapidot, Tsvee

    2016-04-21

    Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols. PMID:27074509

  11. Smooth muscle progenitor cells from peripheral blood promote the neovascularization of endothelial colony-forming cells

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Hyung Joon; Seo, Ha-Rim [Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul (Korea, Republic of); Jeong, Hyo Eun [Department of Mechanical Engineering, Korea University, Seoul (Korea, Republic of); Choi, Seung-Cheol; Park, Jae Hyung; Yu, Cheol Woong; Hong, Soon Jun [Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul (Korea, Republic of); Chung, Seok [Department of Mechanical Engineering, Korea University, Seoul (Korea, Republic of); Lim, Do-Sun, E-mail: dslmd@kumc.or.kr [Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul (Korea, Republic of)

    2014-07-11

    Highlights: • Two distinct vascular progenitor cells are induced from adult peripheral blood. • ECFCs induce vascular structures in vitro and in vivo. • SMPCs augment the in vitro and in vivo angiogenic potential of ECFCs. • Both cell types have synergistic therapeutic potential in ischemic hindlimb model. - Abstract: Proangiogenic cell therapy using autologous progenitors is a promising strategy for treating ischemic disease. Considering that neovascularization is a harmonized cellular process that involves both endothelial cells and vascular smooth muscle cells, peripheral blood-originating endothelial colony-forming cells (ECFCs) and smooth muscle progenitor cells (SMPCs), which are similar to mature endothelial cells and vascular smooth muscle cells, could be attractive cellular candidates to achieve therapeutic neovascularization. We successfully induced populations of two different vascular progenitor cells (ECFCs and SMPCs) from adult peripheral blood. Both progenitor cell types expressed endothelial-specific or smooth muscle-specific genes and markers, respectively. In a protein array focused on angiogenic cytokines, SMPCs demonstrated significantly higher expression of bFGF, EGF, TIMP2, ENA78, and TIMP1 compared to ECFCs. Conditioned medium from SMPCs and co-culture with SMPCs revealed that SMPCs promoted cell proliferation, migration, and the in vitro angiogenesis of ECFCs. Finally, co-transplantation of ECFCs and SMPCs induced robust in vivo neovascularization, as well as improved blood perfusion and tissue repair, in a mouse ischemic hindlimb model. Taken together, we have provided the first evidence of a cell therapy strategy for therapeutic neovascularization using two different types of autologous progenitors (ECFCs and SMPCs) derived from adult peripheral blood.

  12. Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels

    Directory of Open Access Journals (Sweden)

    Barleon Bernhard

    2010-07-01

    Full Text Available Abstract Background Postnatal endothelial progenitor cells (EPCs have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated. Results In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels. Mouse lung microvascular endothelial cells (MLMVECs were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony. These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels. Conclusion The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.

  13. Infectious Haematopoietic Necrosis

    OpenAIRE

    Institute, Marine

    2011-01-01

    This leaflet gives information on infectious haematopoietic necrosis. This disease is caused by a single stranded RNA virus of the family Rhabdoviridae, genus Novirhabdoviridae. IHN is listed as a non-exotic disease under EU Directive 2006/88/EC, and is notifiable in Ireland, according to S.I. No. 261 of 2008.

  14. It Is All in the Blood: The Multifaceted Contribution of Circulating Progenitor Cells in Diabetic Complications

    Directory of Open Access Journals (Sweden)

    Gian Paolo Fadini

    2012-01-01

    Full Text Available Diabetes mellitus (DM is a worldwide growing disease and represents a huge social and healthcare problem owing to the burden of its complications. Micro- and macrovascular diabetic complications arise from excess damage through well-known biochemical pathways. Interestingly, microangiopathy hits the bone marrow (BM microenvironment with features similar to retinopathy, nephropathy and neuropathy. The BM represents a reservoir of progenitor cells for multiple lineages, not limited to the hematopoietic system and including endothelial cells, smooth muscle cells, cardiomyocytes, and osteogenic cells. All these multiple progenitor cell lineages are profoundly altered in the setting of diabetes in humans and animal models. Reduction of endothelial progenitor cells (EPCs along with excess smooth muscle progenitor (SMP and osteoprogenitor cells creates an imbalance that promote the development of micro- and macroangiopathy. Finally, an excess generation of BM-derived fusogenic cells has been found to contribute to diabetic complications in animal models. Taken together, a growing amount of literature attributes to circulating progenitor cells a multi-faceted role in the pathophysiology of DM, setting a novel scenario that puts BM and the blood at the centre of the stage.

  15. The proteoglycan Trol controls proliferation and differentiation of blood progenitors in the Drosophila lymph gland

    Science.gov (United States)

    Grigorian, Melina; Liu, Ting; Banerjee, Utpal; Hartenstein, Volker

    2014-01-01

    The heparin sulfate proteoglycan Trol (Terribly Reduced Optic Lobes) is the D. melanogaster homolog of the vertebrate protein Perlecan. Trol is expressed as part of the extracellular matrix (ECM) found in the hematopoietic organ, called the lymph gland. In the normal lymph gland, the ECM forms thin basement membranes around individual or small groups of blood progenitors. The pattern of basement membranes, reported by Trol expression, is spatio-temporally correlated to hematopoiesis. The central, medullary zone which contain undifferentiated hematopoietic progenitors has many, closely spaced membranes. Fewer basement membranes are present in the outer, cortical zone, where differentiation of blood cells takes place. Loss of trol causes a dramatic change of the ECM into a three-dimensional, spongy mass that fills wide spaces scattered throughout the lymph gland. At the same time proliferation is reduced, leading to a significantly smaller lymph gland. Interestingly, differentiation of blood progenitors in trol mutants is precocious, resulting in the break-down of the usual zonation of the lymph gland which normally consists of an immature center (medullary zone) where cells remain undifferentiated, and an outer cortical zone, where differentiation sets in. We present evidence that the effect of Trol on blood cell differentiation is mediated by Hedgehog (Hh) signaling, which is known to be required to maintain an immature medullary zone. Overexpression of hh in the background of a trol mutation is able to rescue the premature differentiation phenotype. Our data provide novel insight into the role of the ECM component Perlecan during Drosophila hematopoiesis. PMID:23510717

  16. Expansion in bioreactors of human progenitor populations from cord blood and mobilized peripheral blood.

    Science.gov (United States)

    Van Zant, G; Rummel, S A; Koller, M R; Larson, D B; Drubachevsky, I; Palsson, M; Emerson, S G

    1994-01-01

    Umbilical cord blood (UCB) and mobilized peripheral blood (MPB) provide an alternate source to bone marrow for transplantation. Expansion in vitro of stem/progenitor cell populations from these sources may provide adult-sized grafts otherwise not attainable because of the limited cell numbers available in the case of UCB or because of numerous rounds of apheresis required for sufficient MPB cells. We asked whether continuous perfusion culture could be employed in ex vivo expansion to produce clinically relevant numbers of stem/progenitor cells from these sources. To evaluate MPB, 1-10 million leukocytes, from patients who had received either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and granulocyte-macrophage colony-stimulating factor (GM-CSF), were inoculated into bioreactors, with or without irradiated, allogeneic stroma. The growth factor combination in the perfusion medium consisted of interleukin-3 (IL-3), stem cell factor (SCF), GM-CSF and erythropoietin (Epo). Under the best conditions tested, total cell numbers, granulocyte-macrophage colony-forming units (CFU-GM), and long-term culture-initiating cell (LTC-IC) populations were expanded by about 50-, 80-, and 20-fold, respectively, over 14 days. At low cell inocula (1 million), the presence of stroma enhanced the expansion of total cells and CFU-GM but not of LTC-IC. When SCF was not included in the medium, both total cells and CFU-GM expanded to a much lesser extent, but again the expansion of LTC-IC was not affected. At the higher cell inoculum (10 million), expansions of total cells and CFU-GM were equivalent with or without stroma. To evaluate UCB, cells were placed into bioreactors with or without irradiated, allogeneic stroma, and the bioreactors were perfused with medium containing the four standard growth factors. After 6-14 days, in several independent experiments, 20-24 million cells were harvested from bioreactors perfused with SCF-containing medium, irrespective of the

  17. CXCR2 modulates bone marrow vascular repair and haematopoietic recovery post-transplant.

    Science.gov (United States)

    Hale, Sarah J M; Hale, Ashley B H; Zhang, Youyi; Sweeney, Dominic; Fisher, Nita; van der Garde, Mark; Grabowska, Rita; Pepperell, Emma; Channon, Keith; Martin-Rendon, Enca; Watt, Suzanne M

    2015-05-01

    Murine models of bone marrow transplantation show that pre-conditioning regimens affect the integrity of the bone marrow endothelium and that the repair of this vascular niche is an essential pre-requisite for successful haematopoietic stem and progenitor cell engraftment. Little is known about the angiogenic pathways that play a role in the repair of the human bone marrow vascular niche. We therefore established an in vitro humanized model, composed of bone marrow stromal and endothelial cells and have identified several pro-angiogenic factors, VEGFA, ANGPT1, CXCL8 and CXCL16, produced by the stromal component of this niche. We demonstrate for the first time that addition of CXCL8 or inhibition of its receptor, CXCR2, modulates blood vessel formation in our bone marrow endothelial niche model. Compared to wild type, Cxcr2(-/-) mice displayed a reduction in bone marrow cellularity and delayed platelet and leucocyte recovery following myeloablation and bone marrow transplantation. The delay in bone marrow recovery correlated with impaired bone marrow vascular repair. Taken together, our data demonstrate that CXCR2 regulates bone marrow blood vessel repair/regeneration and haematopoietic recovery, and clinically may be a therapeutic target for improving bone marrow transplantation.

  18. The proteoglycan Trol controls proliferation and differentiation of blood progenitors in the Drosophila lymph gland

    OpenAIRE

    Grigorian, Melina; Liu, Ting; Banerjee, Utpal; Hartenstein, Volker

    2013-01-01

    The heparin sulfate proteoglycan Trol (Terribly Reduced Optic Lobes) is the D. melanogaster homolog of the vertebrate protein Perlecan. Trol is expressed as part of the extracellular matrix (ECM) found in the hematopoietic organ, called the lymph gland. In the normal lymph gland, the ECM forms thin basement membranes around individual or small groups of blood progenitors. The pattern of basement membranes, reported by Trol expression, is spatio-temporally correlated to hematopoiesis. The cent...

  19. The convergence of Notch and MAPK signaling specifies the blood progenitor fate in the Drosophila mesoderm

    OpenAIRE

    Grigorian, Melina; Mandal, Lolitika; Hakimi, Manuel; Ortiz, Irma; Hartenstein, Volker

    2011-01-01

    Blood progenitors arise from a pool of pluripotential cells (“hemangioblasts”) within the Drosophila embryonic mesoderm. The fact that the cardiogenic mesoderm consists of only a small number of highly stereotypically patterned cells that can be queried individually regarding their gene expression in normal and mutant embryos, is one of the significant advantages that Drosophila offers to dissect the mechanism specifying the fate of these cells. We show in this paper that the expression of th...

  20. The convergence of Notch and MAPK signaling specifies the blood progenitor fate in the Drosophila mesoderm.

    Science.gov (United States)

    Grigorian, Melina; Mandal, Lolitika; Hakimi, Manuel; Ortiz, Irma; Hartenstein, Volker

    2011-05-01

    Blood progenitors arise from a pool of pluripotential cells ("hemangioblasts") within the Drosophila embryonic mesoderm. The fact that the cardiogenic mesoderm consists of only a small number of highly stereotypically patterned cells that can be queried individually regarding their gene expression in normal and mutant embryos is one of the significant advantages that Drosophila offers to dissect the mechanism specifying the fate of these cells. We show in this paper that the expression of the Notch ligand Delta (Dl) reveals segmentally reiterated mesodermal clusters ("cardiogenic clusters") that constitute the cardiogenic mesoderm. These clusters give rise to cardioblasts, blood progenitors and nephrocytes. Cardioblasts emerging from the cardiogenic clusters accumulate high levels of Dl, which is required to prevent more cells from adopting the cardioblast fate. In embryos lacking Dl function, all cells of the cardiogenic clusters become cardioblasts, and blood progenitors are lacking. Concomitant activation of the Mitogen Activated Protein Kinase (MAPK) pathway by Epidermal Growth Factor Receptor (EGFR) and Fibroblast Growth Factor Receptor (FGFR) is required for the specification and maintenance of the cardiogenic mesoderm; in addition, the spatially restricted localization of some of the FGFR ligands may be instrumental in controlling the spatial restriction of the Dl ligand to presumptive cardioblasts. PMID:21382367

  1. The Chondrogenic Potential of Progenitor Cells Derived from Peripheral Blood: A Systematic Review.

    Science.gov (United States)

    Wang, Shao-Jie; Yin, Meng-Hong; Jiang, Dong; Zhang, Zheng-Zheng; Qi, Yan-Song; Wang, Hai-Jun; Yu, Jia-Kuo

    2016-08-15

    An increasing number of studies have detected mesenchymal stromal cells (MSCs) and mesenchymal progenitor cells (MPCs) in the peripheral blood (PB). This study aimed to systematically review the possibility of using the PB as a source for chondrogenic progenitors. PubMed, the Web of Science, and Embase were searched for relevant articles. The findings of the studies were reviewed to evaluate the biological characteristics of PB-derived MSCs, chondrogenic MPCs, and their applications in cartilage repair. Thirty-six articles were included in the final analysis, 29 of which indicated that PB is a potential source for chondrogenic progenitor cells. Thirty-two studies reporting in vitro data, including 79.2% (19/24) of studies on PB MSCs and 75% (6/8) of studies on chondrogenic PB MPCs, confirmed the existence of PB MSCs and PB MPCs, respectively; all in vivo investigations showed that using PB as a cell source enhanced cartilage repair. PB MSCs were found in most of the animal studies (12/13), whereas 7 of 11 human studies described the presence of PB MSCs. This systematic review strongly indicates the existence of MSCs in the PB of animals, whereas the presence of MSCs in human PB is less clear. Although the presence of both MSCs and chondrogenic MPCs in the PB, as well as a few favorable outcomes associated with the use of PB-derived progenitors for cartilage repair in vivo, suggests that the PB is a potential alternative source of chondrogenic progenitor cells for cartilage repair, the efficacy of these cells has not been compared to those from other sources, such as bone marrow or adipose tissue in controlled studies. PMID:27353075

  2. A Novel Population of Mesenchymal Progenitors with Hematopoietic Potential Originated from CD14- Peripheral Blood Mononuclear Cells

    Directory of Open Access Journals (Sweden)

    Gang Hu, Peng Liu, Jie Feng, Yan Jin

    2011-01-01

    Full Text Available Hemopoietic system derived progenitor cells with mesenchymal features have been identified including CD14+ monocyte-derived progenitors. However, it is unclear whether there are mesenchyme derived progenitors with hematopoietic potential. Herein, we identified a novel CD14- cell-derived population with both mesenchymal and hematopoietic features in rat peripheral blood, and this cell population is different from the CD14+ monocyte-derived progenitors but designated peripheral blood multipotential mesenchymal progenitors (PBMMPs. Phenotype analysis demonstrated expression of mesenchymal markers in PBMMPs including BMPRs, Endoglin/CD105, Fibronectin (Fn, Vimentin (Vim, Collagen (Col I/II/III along with hematopoietic marker CD34. CD14+ cell-derived population shared the same characteristics with CFs. In mixed culture of CD14+ and CD14- cells, PBMMPs were a predominant component and expressed CD29high, CD73high, CD34high, CD45low and CD90. Except for the value of mixed T lymphocytes and CD14+ cell-derived population, hematopoietic characters of cultured PBMMPs were indicated by CD14-/CD34+/CD45-/CD90+. The mesenchymal origin was further confirmed by comparing PBMMPs with bone marrow stromal cells. Finally, we transplanted PBMMPs into a skin wound model, and results showed the specific potential of PBMMPs in not only extracellular matrix secretion but epidermal regeneration. This study provides evidence that peripheral blood contains common hematopoietic-mesenchymal progenitors from both hematopoietic and mesenchymal lineages, and CD34+ mesenchymal progenitors are a possible alternative source of epidermal cells in wound healing.

  3. Myeloid and lymphoid contribution to non-haematopoietic lineages through irradiation-induced heterotypic cell fusion

    DEFF Research Database (Denmark)

    Nygren, J.M.; Liuba, K.; Breitbach, M.;

    2008-01-01

    and Purkinje neurons. However, through lineage fate-mapping we demonstrate that such in vivo fusion of lymphoid and myeloid blood cells does not occur to an appreciable extent in steady-state adult tissues or during normal development. Rather, fusion of blood cells with different non-haematopoietic cell types...... is induced by organ-specific injuries or whole-body irradiation, which has been used in previous studies to condition recipients of bone marrow transplants. Our findings demonstrate that blood cells of the lymphoid and myeloid lineages contribute to various non-haematopoietic tissues by forming rare fusion......Recent studies have suggested that regeneration of non-haematopoietic cell lineages can occur through heterotypic cell fusion with haematopoietic cells of the myeloid lineage. Here we show that lymphocytes also form heterotypic-fusion hybrids with cardiomyocytes, skeletal muscle, hepatocytes...

  4. [Recovery of transplantable hematopoietic progenitor cells from the umbilical cord blood].

    Science.gov (United States)

    Perutelli, P; Murugesan, S

    2001-12-01

    Cord blood (CB) is a source of transplantable hematopoietic progenitor cells (HPC); it represents an alternative to bone marrow to restore hematopoiesis in patients affected by malignant and non-malignant disease. Therefore, large-scale CB banks would be a natural complement to bone marrow donor registries. Storage of unmanipulated whole CB units requires a great number of liquid nitrogen containers. Separation of leukocytes allows CB storage in smaller space, thus lowering banking costs; unfortunately, CB processing may cause significant losses of stem/progenitor cells. We describe here a procedure for erythrocyte removal from CB units by 1 xg sedimentation on Emagel, a gelatin-based colloidal compound commonly used as plasma expander. The erythrocyte-depleted supernatant was collected and then centrifuged to recover the leukocyte pool. We evaluated erythrocyte depletion and leukocyte recovery after different sedimentation time (30, 45 and 60 min), on 139 CB units collected at delivery. All the considered parameters were improved by increasing sedimentation time. Erythrocyte depletion at 60 min was 86.0% and we recovered 93.3% of CD34+ cells. The proposed CB-processing method allowed us to collect a satisfactory amount of HPC in view of stem cell transplantation; it may have a potential role in UCB banking. PMID:11822091

  5. Homing of circulating blood endothelial progenitor cells after myocardial infarction is mediated by Akt-SDF-1-signal pathway

    Institute of Scientific and Technical Information of China (English)

    赵岚

    2013-01-01

    Objective To investigate the expressions of protein kinase B(Akt) and stromal cell-derived factor-1(SDF-1) and their relations with circulating blood endothelial progenitor cell homing after myocardial infarction(MI). Methods MI was induced in the

  6. Effects of spaceflight on rat peripheral blood leukocytes and bone marrow progenitor cells

    Science.gov (United States)

    Ichiki, A. T.; Gibson, L. A.; Jago, T. L.; Strickland, K. M.; Johnson, D. L.; Lange, R. D.; Allebban, Z.

    1996-01-01

    The white blood cell (WBC) elements and the bone marrow myeloid progenitor cell populations were analyzed to ascertain adaptation to micro-gravity and subsequent readaptation to 1 G in rats flown on the 14-day Spacelab Life Sciences-2 (SLS-2) mission. Bone marrow cells were harvested from one group of rats killed inflight (FD13) and blood was drawn from three other groups at various times. The WBC level was normal on FD14 with the exception of neutrophilia. On FD13, numbers of colony-forming units-granulocyte (CFU-G), CFU-GM, and CFU-M from flight animals were decreased compared with ground controls when incubated with recombinant rat interleukin-3 (rrIL-3) alone or in combination with recombinant human erythropoietin (rhEpo). On recovery (R + 0), flight rats had decreased numbers of total leukocytes and absolute numbers of lymphocytes and monocytes with elevated neutrophils compared with control rats. They had lower numbers of CD4, CD8, CD2, CD3, and B cells in the peripheral blood but no differences in spleen lymphocytes.

  7. Genetically engineered blood pharming: generation of HLA-universal platelets derived from CD34+ progenitor cells.

    Science.gov (United States)

    Figueiredo, Constança; Blaszczyk, Rainer

    2014-01-01

    Blood pharming is a recently designed concept to enable in vitro production of blood cells that are safe, effective and readily available. This approach represents an alternative to blood donation and may contribute to overcome the shortage of blood products. However, the high variability of the human leukocyte antigen (HLA) loci remains a major hurdle to the application of off-the-shelf blood products. Refractoriness to platelet (PLT) transfusion caused by alloimmunization against HLA class I antigens constitutes a relevant clinical problem. Thus, it would be desirable to generate PLT units devoid of HLA antigens. To reduce the immunogenicity of cell-based therapeutics, we have permanently reduced HLA class I expression using an RNA interference strategy. Furthermore, we demonstrated that the generation of HLA class I-silenced (HLA-universal) PLTs from CD34+ progenitor cells using an shRNA targeting β2-microglobulin transcripts is feasible. CD34+ progenitor cells derived from G-CSF mobilised donors were transduced with a lentiviral vector encoding for the β2-microglobulin-specific shRNA and differentiated into PLTs using a liquid culture system. The functionality of HLA-silenced PLTs and their ability to escape HLA antibody-mediated cytotoxicity were evaluated in vitro and in vivo. Platelet activation in response to ADP and thrombin were assessed in vitro. The immune-evasion capability of HLA-universal megakaryocytes (MKs) and PLTs was tested in lymphocytotoxicity assays using anti-HLA antibodies. To assess the functionality of HLA-universal PLTs in vivo, HLA-silenced MKs were infused into NOD/SCID/IL-2Rγc(-/-) mice with or without anti-HLA antibodies. PLT generation was evaluated by flow cytometry using anti-CD42a and CD61 antibodies. HLA-universal PLTs demonstrated to be functionally similar to blood-derived PLTs. Lymphocytotoxicity assays showed that HLA-silencing efficiently protects MKs against HLA antibody-mediated complement-dependent cytotoxicity. 80

  8. Genetically engineered blood pharming: generation of HLA-universal platelets derived from CD34+ progenitor cells.

    Science.gov (United States)

    Figueiredo, Constança; Blaszczyk, Rainer

    2014-01-01

    Blood pharming is a recently designed concept to enable in vitro production of blood cells that are safe, effective and readily available. This approach represents an alternative to blood donation and may contribute to overcome the shortage of blood products. However, the high variability of the human leukocyte antigen (HLA) loci remains a major hurdle to the application of off-the-shelf blood products. Refractoriness to platelet (PLT) transfusion caused by alloimmunization against HLA class I antigens constitutes a relevant clinical problem. Thus, it would be desirable to generate PLT units devoid of HLA antigens. To reduce the immunogenicity of cell-based therapeutics, we have permanently reduced HLA class I expression using an RNA interference strategy. Furthermore, we demonstrated that the generation of HLA class I-silenced (HLA-universal) PLTs from CD34+ progenitor cells using an shRNA targeting β2-microglobulin transcripts is feasible. CD34+ progenitor cells derived from G-CSF mobilised donors were transduced with a lentiviral vector encoding for the β2-microglobulin-specific shRNA and differentiated into PLTs using a liquid culture system. The functionality of HLA-silenced PLTs and their ability to escape HLA antibody-mediated cytotoxicity were evaluated in vitro and in vivo. Platelet activation in response to ADP and thrombin were assessed in vitro. The immune-evasion capability of HLA-universal megakaryocytes (MKs) and PLTs was tested in lymphocytotoxicity assays using anti-HLA antibodies. To assess the functionality of HLA-universal PLTs in vivo, HLA-silenced MKs were infused into NOD/SCID/IL-2Rγc(-/-) mice with or without anti-HLA antibodies. PLT generation was evaluated by flow cytometry using anti-CD42a and CD61 antibodies. HLA-universal PLTs demonstrated to be functionally similar to blood-derived PLTs. Lymphocytotoxicity assays showed that HLA-silencing efficiently protects MKs against HLA antibody-mediated complement-dependent cytotoxicity. 80

  9. Replication of parvovirus B19 in hematopoietic progenitor cells generated in vitro from normal human peripheral blood.

    OpenAIRE

    Schwarz, T F; Serke, S; Hottenträger, B; von Brunn, A; Baurmann, H; Kirsch, A.; Stolz, W.; Huhn, D; Deinhardt, F.; Roggendorf, M

    1992-01-01

    Erythroid progenitor cells generated in vitro from peripheral human blood in the presence of interleukin-3 and erythropoietin were infected with human parvovirus B19. B19 virus DNA replication was highest 48 to 72 h after infection, and maximum levels of B19 virus proteins were detected in culture supernatants at 72 to 96 h after infection. B19 virus propagated in vitro was infectious. This cell culture system with peripheral blood cells facilitates studies in vitro of B19 virus replication.

  10. Differentiation of smooth muscle progenitor cells in peripheral blood and its application in tissue engineered blood vessels

    Institute of Scientific and Technical Information of China (English)

    Shang-zhe XIE; Ning-tao FANG; Shui LIU; Ping ZHOU; Yi ZHANG; Song-mei WANG; Hong-yang GAO; Luan-feng PAN

    2008-01-01

    Background: A major shortcoming in tissue engineered blood vessels (TEBVs) is the lack of healthy and easily attainable smooth muscle cells (SMCs). Smooth muscle progenitor cells (SPCs), especially from peripheral blood, may offer an alternative cell source for tissue engineering involving a less invasive harvesting technique. Methods: SPCs were isolated from 5-ml fresh rat peripheral blood by density-gradient centrifugation and cultured for 3 weeks in endothelial growth medium-2-MV (EGM-2-MV) medium containing platelet-derived growth factor-BB (PDGF BB). Before seeded on the synthesized scaffold, SPC-derived smooth muscle outgrowth cell (SOC) phenotypes were assessed by immuno-fluorescent staining, Western blot analysis, and reverse transcription polymerase chain reaction (RT-PCR). The cells were seeded onto the silk fibroin-modified poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (SF-PHBHHx) scaffolds by 6×104 cells/cm'2 and cultured under the static con-dition for 3 weeks. The growth and proliferation of the seeded cells on the scaffold were analyzed by 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT) assay, scanning electron microscope (SEM), and 4,6-diamidino-2-phenylindole (DAPI) staining. Results: SOCs displayed specific "hill and valley" morphology, expressed the specific markers of the SMC lineage: protein, and extracellular matrix components elastin and matrix Gla protein (MGP), as well as vascular endothelial growth factor (VEGF). After seeded on the SF-PHBHHx scaffold, the cells showed excellent metabolic activity and proliferation. Conclusion: SPCs isolated from peripheral blood can be differentiated into the SMCs in vitro and have an impressive growth potential in the biodegradable synthesized scaffold. Thus, SPCs may be a promising cell source for constructing TEBVs.

  11. CXC chemokine receptor 3 expression on CD34(+) hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor

    DEFF Research Database (Denmark)

    Jinquan, T; Quan, S; Jacobi, H H;

    2000-01-01

    expressed on CD34(+) hematopoietic progenitors from human cord blood stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) but not on freshly isolated CD34(+) progenitors. Freshly isolated CD34(+) progenitors expressed low levels of CXCR3 messenger RNA, but this expression was highly up......-induced CD34(+) progenitor chemotaxis. These chemotactic attracted CD34(+) progenitors are colony-forming units-granulocyte-macrophage. gamma IP-10 and Mig also induced GM-CSF-stimulated CD34(+) progenitor adhesion and aggregation by means of CXCR3, a finding confirmed by the observation that anti-CXCR3 m...... stimulated CXCR3 redistribution and cellular polarization in GM-CSF-stimulated CD34(+) progenitors. These results indicate that CXCR3-gamma IP-10 and CXCR3-Mig receptor-ligand pairs, as well as the effects of GM-CSF on them, may be especially important in the cytokine/chemokine environment...

  12. Collection of peripheral progenitor cells: a comparison between Amicus and Cobe-Spectra blood cell separators.

    Science.gov (United States)

    Adorno, Gaspare; Del Proposto, Gianpaolo; Palombi, Francesca; Bruno, Antonio; Ballatore, Giovanna; Postorino, Massimiliano; Tendas, Andrea; Del Poeta, Giovanni; Isacchi, Giancarlo; Amadori, Sergio

    2004-04-01

    The authors compared the efficiency of two different blood cell separators (Amicus and Cobe-Spectra) in collecting peripheral blood progenitor cells for autologous or homologous transplantation. A total number of 129 procedures were performed, 36 with Spectra, 93 with Amicus. There was no difference between Spectra and Amicus efficiencies for CD34+ cell collection (46.685% vs 46.235%; p=n.s) but the platelet efficiencies were 17.31% and 12.54% respectively (p=0.04) and, if autologous and allogeneic collections were considered separately, a marked difference resulted in allogeneic platelet efficiency between 6 Spectra and 23 Amicus procedures (26.83% vs 8.68%, p=0.0004). The authors were able to demonstrate that in 70 Amicus autologous collections there was a different platelet efficiency, if peripheral count was considered: 12 procedures performed with a platelet count > 100 x 10(9)/l had a very low efficiency (6.86%), but this value increased if platelet count lowered (13.02% if between 100 and 50 x 10(9)/l, 22.63% if between 50 and 0 x 10(9)/l, 23 and 35 procedures respectively). The study is preliminary and the number of collections is little, but the overall data suggest that Spectra (AutoPBSC, V 6.0) and Amicus separators have the same efficiency for collecting CD34+ cells while Amicus procedures have a very low platelet contamination, especially with donors.

  13. Endothelial progenitor cell differentiation using cryopreserved, umbilical cord blood-derived mononuclear cells

    Institute of Scientific and Technical Information of China (English)

    Jun-ho JANG; Hugh C KIM; Sun-kyung KIM; Jeong-eun CHOI; Young-jin KIM; Hyun-woo LEE; Seok-yun KANG; Joon-seong PARK; Jin-hyuk CHOI; Ho-yeong LIM

    2007-01-01

    Aim: To investigate the endothelial differentiation potentiality of umbilical cord blood (UCB), we induced the differentiation of endothelial progenitor cells (EPC)from cryopreserved UCB-derived mononuclear cells (MNC). Methods: MNC from cryopreserved UCB and peripheral blood (PB) were cultured in M199 medium with endothelial cell growth supplements for 14 d. EPC were characterized by RT-PCR,flow cytometry, and immunocytochemistry analysis. The proliferation of differen-tiated EPC was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTI') assay, and vascular endothelial growth factor (VEGF) concentra-tion was measured using an ELISA kit. Characteristics of UCB-derived EPC were compared with those of PB-derived EPC. Results: A number of round-shaped cells were loosely attached to the bottom after 24 h culture, and numerous spindle-shaped cells began to appear from the round-shaped ones on d 7. Those cells expressed endothelial markers such as, Fit-1/VEGFR-1, ecNOS, VE-cadherin, yon Willebrand factor, and secreted VEGF. The patterns of endothelial markers of EPC from PB and UCB did not show striking differences. The results of the prolifera-tion and secretion of VEGF were also similar. Conclusion: We successfully cul-tured UCB cells stored at -196 ℃ into cells with the quality of endothelial cells.Those EPC could be used for angiogenic therapeutics by activating adjacent endothelial cells and enhancing angiogenesis.

  14. The non-haematopoietic biological effects of erythropoietin.

    Science.gov (United States)

    Arcasoy, Murat O

    2008-04-01

    In the haematopoietic system, the principal function of erythropoietin (Epo) is the regulation of red blood cell production, mediated by its specific cell surface receptor (EpoR). Following the cloning of the Epo gene (EPO) and characterization of the selective haematopoietic action of Epo in erythroid lineage cells, recombinant Epo forms (epoetin-alfa, epoetin-beta and the long-acting analogue darbepoetin-alfa) have been widely used for treatment of anaemia in chronic kidney disease and chemotherapy-induced anaemia in cancer patients. Ubiquitous EpoR expression in non-erythroid cells has been associated with the discovery of diverse biological functions for Epo in non-haematopoietic tissues. During development, Epo-EpoR signalling is required not only for fetal liver erythropoiesis, but also for embryonic angiogenesis and brain development. A series of recent studies suggest that endogenous Epo-EpoR signalling contributes to wound healing responses, physiological and pathological angiogenesis, and the body's innate response to injury in the brain and heart. Epo and its novel derivatives have emerged as major tissue-protective cytokines that are being investigated in the first human studies involving neurological and cardiovascular diseases. This review focuses on the scientific evidence documenting the biological effects of Epo in non-haematopoietic tissues and discusses potential future applications of Epo and its derivatives in the clinic. PMID:18324962

  15. Efficient removal of platelets from peripheral blood progenitor cell products using a novel micro-chip based acoustophoretic platform.

    Directory of Open Access Journals (Sweden)

    Josefina Dykes

    Full Text Available BACKGROUND: Excessive collection of platelets is an unwanted side effect in current centrifugation-based peripheral blood progenitor cell (PBPC apheresis. We investigated a novel microchip-based acoustophoresis technique, utilizing ultrasonic standing wave forces for the removal of platelets from PBPC products. By applying an acoustic standing wave field onto a continuously flowing cell suspension in a micro channel, cells can be separated from the surrounding media depending on their physical properties. STUDY DESIGN AND METHODS: PBPC samples were obtained from patients (n = 15 and healthy donors (n = 6 and sorted on an acoustophoresis-chip. The acoustic force was set to separate leukocytes from platelets into a target fraction and a waste fraction, respectively. The PBPC samples, the target and the waste fractions were analysed for cell recovery, purity and functionality. RESULTS: The median separation efficiency of leukocytes to the target fraction was 98% whereas platelets were effectively depleted by 89%. PBPC samples and corresponding target fractions were similar in the percentage of CD34+ hematopoetic progenitor/stem cells as well as leukocyte/lymphocyte subset distributions. Median viability was 98%, 98% and 97% in the PBPC samples, the target and the waste fractions, respectively. Results from hematopoietic progenitor cell assays indicated a preserved colony-forming ability post-sorting. Evaluation of platelet activation by P-selectin (CD62P expression revealed a significant increase of CD62P+ platelets in the target (19% and waste fractions (20%, respectively, compared to the PBPC input samples (9%. However, activation was lower when compared to stored blood bank platelet concentrates (48%. CONCLUSION: Acoustophoresis can be utilized to efficiently deplete PBPC samples of platelets, whilst preserving the target stem/progenitor cell and leukocyte cell populations, cell viability and progenitor cell colony-forming ability

  16. Changes of Number and Function of Late Endothelial Progenitor Cells in Peripheral Blood of COPD Patients Combined with Pulmonary Hypertension.

    Science.gov (United States)

    Liu, Pei; Zhang, Hongmei; Liu, Jianxin; Sheng, Chunfeng; Zhang, Linlin; Zeng, Yanjun

    2016-06-01

    Objective The objective of this study was to investigate the changes of number and function of late endothelial progenitor cells (EPCs) in peripheral blood of chronic obstructive pulmonary disease (COPD) patients combined with pulmonary hypertension. Subjects and Methods The study enrolled 120 cases including 40 non-COPD and pulmonary arterial hypertension (PAH) patients (non-COPD group), 40 COPD non-PAH patients (COPD group), and 40 COPD patients combined with PAH (COPD + PAH group). Peripheral blood mononuclear cells were separated by density gradient centrifugation, cultured for 21 days, and then identified as late endothelial progenitor cells. The cell colonies were counted. MTT assay, modified Boyden chamber assay, and human fibronectin plates were used to measure the proliferation, migration, and adhesion functions of the late endothelial progenitor cells, respectively. Results Compared with non-COPD and COPD groups, the number of peripheral blood late EPCs in COPD + PAH group was significantly reduced, and the proliferation, adhesion, and migration capacities were significantly lowered; the differences were statistically significant (p number and function of late EPCs decreased with the increase of pulmonary artery pressure (p number of late EPCs in COPD patients combined with pulmonary hypertension was reduced, which implies the impaired cell functions. The changes of number and function were negatively correlated with the severity of pulmonary hypertension.

  17. Detection of clonal immunoglobulin gene rearrangements in the peripheral blood progenitor cells of patients with multiple myeloma: the potential role of purging with CD34 positive selection

    OpenAIRE

    Owen, R. G.; Haynes, A P; Evans, P A; R. J. Johnson; Rawstron, A. C.; McQuaker, G; Smith, G.M; Galvin, M. C.; Barnard, D L; Russell, N H; Child, J. A.; Morgan, G J

    1996-01-01

    Aims—To determine the extent of clonal cell contamination of peripheral blood progenitor cell (PBPC) collections in patients with multiple myeloma (MM) and to assess the purging efficacy of CD34 positive selection.

  18. Number and function of peripheral blood endothelial progenitor cells in Henoch-Schönlein purpura nephritis children with different degrees of renal vascular lesions

    OpenAIRE

    DANG, XI-QIANG; HE, XIAO-JIE; CHEN, HAI-XIA; HE, QING-NAN; Yi, Zhu-Wen

    2012-01-01

    The aim of this study was to explore the correlation between different degrees of renal vascular lesions in children with Henoch-Schönlein purpura nephritis (HSPN) and changes in progenitor cell number and function in peripheral blood. Forty-eight HSPN patients were divided into three groups, mild, moderate and severe, according to the degree of renal vascular lesions. Peripheral blood mononuclear cells were isolated and cultured. Endothelial progenitor cells (EPCs) were identified by immunof...

  19. Sox7-sustained expression alters the balance between proliferation and differentiation of hematopoietic progenitors at the onset of blood specification.

    Science.gov (United States)

    Gandillet, Arnaud; Serrano, Alicia G; Pearson, Stella; Lie-A-Ling, Michael; Lacaud, Georges; Kouskoff, Valerie

    2009-11-26

    The molecular mechanisms that regulate the balance between proliferation and differentiation of precursors at the onset of hematopoiesis specification are poorly understood. By using a global gene expression profiling approach during the course of embryonic stem cell differentiation, we identified Sox7 as a potential candidate gene involved in the regulation of blood lineage formation from the mesoderm germ layer. In the present study, we show that Sox7 is transiently expressed in mesodermal precursors as they undergo specification to the hematopoietic program. Sox7 knockdown in vitro significantly decreases the formation of both primitive erythroid and definitive hematopoietic progenitors as well as endothelial progenitors. In contrast, Sox7-sustained expression in the earliest committed hematopoietic precursors promotes the maintenance of their multipotent and self-renewing status. Removal of this differentiation block driven by Sox7-enforced expression leads to the efficient differentiation of hematopoietic progenitors to all erythroid and myeloid lineages. This study identifies Sox7 as a novel and important player in the molecular regulation of the first committed blood precursors. Furthermore, our data demonstrate that the mere sustained expression of Sox7 is sufficient to completely alter the balance between proliferation and differentiation at the onset of hematopoiesis.

  20. The ageing haematopoietic stem cell compartment

    NARCIS (Netherlands)

    Geiger, Hartmut; de Haan, Gerald; Florian, M. Carolina

    2013-01-01

    Stem cell ageing underlies the ageing of tissues, especially those with a high cellular turnover. There is growing evidence that the ageing of the immune system is initiated at the very top of the haematopoietic hierarchy and that the ageing of haematopoietic stem cells (HSCs) directly contributes t

  1. Human cord blood CD34+ progenitor cells acquire functional cardiac properties through a cell fusion process.

    Science.gov (United States)

    Avitabile, Daniele; Crespi, Alessia; Brioschi, Chiara; Parente, Valeria; Toietta, Gabriele; Devanna, Paolo; Baruscotti, Mirko; Truffa, Silvia; Scavone, Angela; Rusconi, Francesca; Biondi, Andrea; D'Alessandra, Yuri; Vigna, Elisa; Difrancesco, Dario; Pesce, Maurizio; Capogrossi, Maurizio C; Barbuti, Andrea

    2011-05-01

    The efficacy of cardiac repair by stem cell administration relies on a successful functional integration of injected cells into the host myocardium. Safety concerns have been raised about the possibility that stem cells may induce foci of arrhythmia in the ischemic myocardium. In a previous work (36), we showed that human cord blood CD34(+) cells, when cocultured on neonatal mouse cardiomyocytes, exhibit excitation-contraction coupling features similar to those of cardiomyocytes, even though no human genes were upregulated. The aims of the present work are to investigate whether human CD34(+) cells, isolated after 1 wk of coculture with neonatal ventricular myocytes, possess molecular and functional properties of cardiomyocytes and to discriminate, using a reporter gene system, whether cardiac differentiation derives from a (trans)differentiation or a cell fusion process. Umbilical cord blood CD34(+) cells were isolated by a magnetic cell sorting method, transduced with a lentiviral vector carrying the enhanced green fluorescent protein (EGFP) gene, and seeded onto primary cultures of spontaneously beating rat neonatal cardiomyocytes. Cocultured EGFP(+)/CD34(+)-derived cells were analyzed for their electrophysiological features at different time points. After 1 wk in coculture, EGFP(+) cells, in contact with cardiomyocytes, were spontaneously contracting and had a maximum diastolic potential (MDP) of -53.1 mV, while those that remained isolated from the surrounding myocytes did not contract and had a depolarized resting potential of -11.4 mV. Cells were then resuspended and cultured at low density to identify EGFP(+) progenitor cell derivatives. Under these conditions, we observed single EGFP(+) beating cells that had acquired an hyperpolarization-activated current typical of neonatal cardiomyocytes (EGFP(+) cells, -2.24 ± 0.89 pA/pF; myocytes, -1.99 ± 0.63 pA/pF, at -125 mV). To discriminate between cell autonomous differentiation and fusion, EGFP(+)/CD34

  2. CXCR2 modulates bone marrow vascular repair and haematopoietic recovery post-transplant

    OpenAIRE

    Hale, Sarah J M; Hale, Ashley B H; Zhang, Youyi; Sweeney, Dominic; Fisher, Nita; van der Garde, Mark; Grabowska, Rita; Pepperell, Emma; Channon, Keith; Martin-Rendon, Enca; Watt, Suzanne M

    2015-01-01

    Murine models of bone marrow transplantation show that pre-conditioning regimens affect the integrity of the bone marrow endothelium and that the repair of this vascular niche is an essential pre-requisite for successful haematopoietic stem and progenitor cell engraftment. Little is known about the angiogenic pathways that play a role in the repair of the human bone marrow vascular niche. We therefore established an in vitro humanized model, composed of bone marrow stromal and endothelial cel...

  3. Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Pospisil, M.; Hofer, M.; Netikova, J.; Hola, J.; Vacek, A. [Academy of Sciences of the Czech Republic, Inst. of Biophysics, Brno (Czech Republic); Znojil, V.; Vacha, J. [Masaryk Univ., Medical Faculty, Brno (Czech Republic)

    1998-03-01

    The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of {sup 60}Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multi-lineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive state induced by radiation exposure. (au) 43 refs.

  4. Development of early PCLP1-expressing haematopoietic cells within the avian dorsal aorta.

    Science.gov (United States)

    Suonpää, P; Kohonen, P; Koskela, K; Koskiniemi, H; Salminen-Mankonen, H; Lassila, O

    2005-09-01

    The first haematopoietic stem cells (HSC) develop in the dorsal aorta as haematopoietic intra-aortic clusters (HIAC). To evaluate the initial steps of definitive haematopoiesis, we have studied the emergence and the expression profile of podocalyxin-like protein 1 (PCLP1)-expressing cells in early chick embryos. Here we demonstrate that at embryonic day 2 (E2), the PCLP1+ cells are present in the splanchnic mesoderm and in the ventral lining of the paired dorsal aorta. Following aortic fusion at E3, the PCLP1-expressing cells are exclusively found in the aortic floor and as the development proceeds, both the haematopoietic clusters and the aortic endothelial cells express PCLP1. In parallel with the early PCLP1 expression, bone morphogenetic protein 4 (BMP4) expression was detected in the splanchnopleura and thereafter in the densely packed mesenchymal cells beneath the HIAC. The microarray analyses of early E3 PCLP1+ cells revealed elevated expression of genes known to be involved in the stem cell function. These data suggest that splanchnopleura-derived PCLP1-expressing cells give rise to the earliest definitive haematopoietic progenitors. PMID:16179008

  5. Scanning of Bone Marrow in Haematopoietic Disorders

    International Nuclear Information System (INIS)

    Scanning can help evaluate size and distribution of the haematopoietic marrow, a difficult task by aspiration or biopsy. With the 61-hole focusing gold-tungsten Oak Ridge National Laboratory Scanner, the marrow organ has been clearly delineated by means of intravenous colloidal Au198, it being known that reticulo-endothelial function in the marrow correlates with areas of haematopoiesis. Patients with normal haematopoiesis and with a variety of blood disorders such as focal marrow lesions, acute and chronic leukaemia, polycythaemiavera, myelofibrosis, multiple myeloma, and lymphoma have been scanned. Because of the reticulo-endothelial activity in liver and spleen, the marrow pattern is obscured in the mid-trunk. Vertebral bodies, intervertebral discs, pelvis and long bones are outlined, and, in the thorax, the sternum and thoracic vertebrae. Focal lesions have also been found. Because of respiratory motion, individual ribs are not seen. In expanded marrow, the knee region can be shown, including the joint space. It has been possible to correlate these scans with aspiration biopsy and with linear scans. Because relatively large doses of Au198 are required, other isotopes are being investigated. An improved whole- body scanner is being tested for more practical scans. (author)

  6. Differential diagnosis of skin lesions after allogeneic haematopoietic stem cell transplantation

    NARCIS (Netherlands)

    Canninga-van Dijk, MR; Sanders, CJ; Verdonck, LF; Fijnheer, R; van den Tweel, JG

    2003-01-01

    Allogeneic haematopoietic stem cell transplantation (i.e. bone marrow or peripheral blood stem cell transplantation) is a common procedure in the treatment of various haematological disorders such as aplastic anaemia, (pre)leukaemias, some malignant lymphomas, multiple myeloma and immunodeficiency s

  7. Human haemato-endothelial precursors: cord blood CD34+ cells produce haemogenic endothelium.

    Directory of Open Access Journals (Sweden)

    Elvira Pelosi

    Full Text Available Embryologic and genetic evidence suggest a common origin of haematopoietic and endothelial lineages. In the murine embryo, recent studies indicate the presence of haemogenic endothelium and of a common haemato-endothelial precursor, the haemangioblast. Conversely, so far, little evidence supports the presence of haemogenic endothelium and haemangioblasts in later stages of development. Our studies indicate that human cord blood haematopoietic progenitors (CD34+45+144-, triggered by murine hepatocyte conditioned medium, differentiate into adherent proliferating endothelial precursors (CD144+CD105+CD146+CD31+CD45- capable of functioning as haemogenic endothelium. These cells, proven to give rise to functional vasculature in vivo, if further instructed by haematopoietic growth factors, first switch to transitional CD144+45+ cells and then to haematopoietic cells. These results highlight the plasticity of haemato-endhothelial precursors in human post-natal life. Furthermore, these studies may provide highly enriched populations of human post-fetal haemogenic endothelium, paving the way for innovative projects at a basic and possibly clinical level.

  8. Therapeutic neovascularization by autologous transplantation with expanded endothelial progenitor cells from peripheral blood into ischemic hind limbs

    Institute of Scientific and Technical Information of China (English)

    Chun-ling FAN; Ping-jin GAO; Zai-qian CHE; Jian-jun LIU; Jian WEI; Ding-liang ZHU

    2005-01-01

    Aim: To investigate the hypothesis that transplantation with expanded autologous endothelial progenitor cells (EPC) could enhance neovascularization.Methods: Peripheral blood mononuclear cells (PB-MNC) isolated from New Zealand White rabbits were cultured in vitro. At d 7, the adherent cells were collected for autologous transplantation. Rabbits with severe unilateral hind limb ischemia were randomly assigned to receive phosphate-buffered saline or expanded EPC in phosphate-buffered saline, administered by intramuscular injection in 6 sites of the ischemic thigh at postoperative d 7. Neovascularization was monitored by using the calf blood pressure ratio to indicate tissue perfusion, digital subtraction angiography to identify collateral vessel development and histological analysis of capillary density in the ischemic limb at d 35 after surgery. Results: Autologous EPC transplantation produced significant amelioration in ischemic hind limbs,as indicated by a greater calf blood pressure ratio (0.52±0.04 vs 0.42±0.05, P<0.01),angiographic score (1.44±0.06 vs 0.98±0.08, P<0.01) and capillary density in muscle (195.2±5.4/mm2 vs 169.4±6.4/mm2, P<0.05), than controls. Conclusion: Transplantation of autologous expanded EPC can promote neovascularization in ischemic hindlimbs.

  9. S phase entry of neural progenitor cells correlates with increased blood flow in the young subventricular zone.

    Directory of Open Access Journals (Sweden)

    Benjamin Lacar

    Full Text Available The postnatal subventricular zone (SVZ contains proliferating neural progenitor cells in close proximity to blood vessels. Insults and drug treatments acutely stimulate cell proliferation in the SVZ, which was assessed by labeling cells entering S phase. Although G1-to-S progression is metabolically demanding on a minute-to-hour time scale, it remains unknown whether increased SVZ cell proliferation is accompanied by a local hemodynamic response. This neurovascular coupling provides energy substrates to active neuronal assemblies. Transcardial dye perfusion revealed the presence of capillaries throughout the SVZ that constrict upon applications of the thromboxane A(2 receptor agonist U-46119 in acute brain slice preparations. We then monitored in vivo blood flow using laser Doppler flowmetry via a microprobe located either in the SVZ or a mature network. U-46119 injections into the lateral ventricle decreased blood flow in the SVZ and the striatum, which are near the ventricle. A 1-hour ventricular injection of epidermal and basic fibroblast growth factor (EGF and bFGF significantly increased the percentage of Sox2 transcription factor-positive cells in S phase 1.5 hours post-injection. This increase was accompanied by a sustained rise in blood flow in the SVZ but not in the striatum. Direct growth factor injections into the cortex did not alter local blood flow, ruling out direct effects on capillaries. These findings suggest that an acute increase in the number of G1-to-S cycling SVZ cells is accompanied by neurometabolic-vascular coupling, which may provide energy and nutrient for cell cycle progression.

  10. Effect of low-dose methylprednisolone on peripheral blood endothelial progenitor cells and its significance in rats after brain injury

    Directory of Open Access Journals (Sweden)

    Bin ZHANG

    2011-05-01

    Full Text Available Objective To explore the effects of low-dose methylprednisolone(MP treatment after traumatic brain injury(TBI in rats on the number of peripheral blood endothelial progenitor cells(EPCs and injury area of the brain.Methods One hundred and fifty-four adult male Wistar rats were involved in the present study,and they were randomly divided into normal control group(n=18,TBI control group(n=38,MP control group(n=30,MP+TBI group(n=30 and TBI+MP group(n=38.The TBI model was reproduced by fluid percussion injury(FPI.MP(5mg/kg was intraperitoneally administered once a day for 4 days.Peripheral venous blood samples were taken on day 1,3,7 and 14,and the counts of EPCs were determined by flow cytometry.The rats were sacrificed on day 1 and 3,brain edema was estimated by dry-wet weight method,and the blood-brain barrier(BBB permeability was determined by Evans-blue extravasation.Results The counts of peripheral blood EPCs were significantly higher in MP control group,MP+TBI group and TBI+MP group on day 1,3 and 7 than that in normal control and TBI control group,and it returned to the level of normal control group on day 14.The BBB permeability was improved and brain edema alleviated in MP+TBI and TBI+MP group on day 3.Conclusion The administration of low-dose MP may increase the count of peripheral blood EPCs in rats,decrease BBB damage,and alleviate brain edema.

  11. Preliminary evaluation of treatment efficacy of umbilical cord blood-derived mesenchymal stem cell-differentiated cardiac pro-genitor cells in a myocardial injury mouse model

    Directory of Open Access Journals (Sweden)

    Truc Le-Buu Pham

    2015-12-01

    Full Text Available Recently, stem cell therapy has been investigated as a strategy to prevent or reverse damage to heart tissue. Although the results of cell transplantation in animal models and patients with myocardial ischemia are promising, the selection of the appropriate cell type remains an issue that requires consideration. In this study, we aimed to evaluate the effect of cardiac progenitor cell transplantation in a mouse model of myocardial ischemia. The cardiac progenitor cells used for transplantation were differentiated from umbilical cord blood mesenchymal stem cells. Animal models injected with phosphate-buffered saline (PBS and healthy mice were used as controls. Cell grafting was assessed by changes in blood pressure and histological evaluation. After 14 days of transplantation, the results demonstrated that the blood pressure of transplanted mice was stable, similar to healthy mice, whereas it fluctuated in PBS-injected mice. Histological analysis showed that heart tissue had regenerated in transplanted mice, but remained damaged in PBS-injected mice. Furthermore, trichrome staining revealed that the transplanted mice did not generate significant amount of scar tissue compared with PBS-injected control mice. In addition, the cardiac progenitor cells managed to survive and integrate with local cells in cell-injected heart tissue 14 days after transplantation. Most importantly, the transplanted cells did not exhibit tumorigenesis. In conclusion, cardiac progenitor cell transplantation produced a positive effect in a mouse model of myocardial ischemia. [Biomed Res Ther 2015; 2(12.000: 435-445

  12. Hypoxia/hypercapnia-induced adaptation maintains functional capacity of cord blood stem and progenitor cells at 4°C.

    Science.gov (United States)

    Vlaski, Marija; Negroni, Luc; Kovacevic-Filipovic, Milica; Guibert, Christelle; Brunet de la Grange, Philippe; Rossignol, Rodrigue; Chevaleyre, Jean; Duchez, Pascale; Lafarge, Xavier; Praloran, Vincent; Schmitter, Jean-Marie; Ivanovic, Zoran

    2014-12-01

    We analyzed the effect of exposure to hypoxic/hypercapnic (HH) gas mixture (5% O2 /9% CO2 ) on the maintenance of functional cord blood CD34(+) hematopoietic stem and progenitor cells in severe hypothermia (4°C) employing the physiological and proteomic approaches. Ten-day exposure to HH maintained the Day 0 (D-0) level of hematopoietic stem cells as detected in vivo on the basis of hematopoietic repopulation of immunodeficient mice-short-term scid repopulating cells (SRC). Conversely, in the atmospheric air (20% O2 /0.05% CO2 ), usual condition used for cell storage at 4°C, stem cell activity was significantly decreased. Also, HH doubled the survival of CD34(+) cells and committed progenitors (CFCs) with respect to the atmospheric air (60% vs. 30%, respectively). Improved cell maintenance in HH was associated with higher proportion of aldehyde dehydrogenase (ALDH) positive cells. Cell-protective effects are associated with an improved maintenance of the plasma and mitochondrial membrane potential and with a conversion to the glycolytic energetic state. We also showed that HH decreased apoptosis, despite a sustained ROS production and a drop of ATP amount per viable cell. The proteomic study revealed that the global protein content was better preserved in HH. This analysis identified: (i) proteins sensitive or insensitive to hypothermia irrespective of the gas phase, and (ii) proteins related to the HH cell-protective effect. Among them are some protein families known to be implicated in the prolonged survival of hibernating animals in hypothermia. These findings suggest a way to optimize short-term cell conservation without freezing.

  13. Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf

    Science.gov (United States)

    Labi, Verena; Bertele, Daniela; Woess, Claudia; Tischner, Denise; Bock, Florian J; Schwemmers, Sven; Pahl, Heike L; Geley, Stephan; Kunze, Mirjam; Niemeyer, Charlotte M; Villunger, Andreas; Erlacher, Miriam

    2013-01-01

    Anti-apoptotic Bcl-2 family members are critical for the regulation of haematopoietic stem and progenitor cell (HSPC) survival. Little is known about the role of their pro-apoptotic antagonists, i.e. ‘BH3-only’ proteins, in this cell compartment. Based on the analysis of cytokine deprivation-induced changes in mRNA expression levels of Bcl-2 family proteins, we determined the consequences of BH3-only protein depletion on HSPC survival in culture and, for selected candidates, on engraftment in vivo. Thereby, we revealed a critical role for Bim and Bmf as regulators of HSPC dynamics both during early engraftment and long-term reconstitution. HSPCs derived from wild-type donors were readily displaced by Bim- or Bmf-deficient or Bcl-2-overexpressing HSPCs as early as 10 days after engraftment. Moreover, in the absence of Bim, significantly lower numbers of transplanted HSPCs were able to fully engraft radio-depleted recipients. Finally, we provide proof of principle that RNAi-based reduction of BIM or BMF, or overexpression of BCL-2 in human CD34+ cord blood cells may be an attractive therapeutic option to increase stem cell survival and transplantation efficacy. PMID:23180554

  14. Principles of bone marrow processing and progenitor cell/mononuclear cell concentrate collection in a continuous flow blood cell separation system.

    Science.gov (United States)

    Hester, J P; Rondón, G; Huh, Y O; Lauppe, M J; Champlin, R E; Deisseroth, A B

    1995-08-01

    The application of continuous flow apheresis technology to processing bone marrow for collection of the mononuclear progenitor cell population appears to follow the same principles as collection of mononuclear cells from peripheral blood. Unlike peripheral blood, however, where mobilization of cells from extravascular sites during the procedures contributes significantly to the final cell yield, the entire quantity of progenitor cells available for recovery from marrow is present in the original marrow when it is pooled. The process then becomes one of attempting optimal recovery of the cells of interest while excluding contaminating erythrocytes and cells of the myeloid series. This study reports the development of a protocol for recovery of MNC, CD33+, CD34+, and CD34+/DR- cells from harvested marrow for autologous and allogeneic transplants using a continuous flow blood cell separator, the variables influencing the recovery of the cells of interest and the clinical response to infusion of the processed cells.

  15. Lin- CD34hi CD117int/hi FcεRI+ cells in human blood constitute a rare population of mast cell progenitors.

    Science.gov (United States)

    Dahlin, Joakim S; Malinovschi, Andrei; Öhrvik, Helena; Sandelin, Martin; Janson, Christer; Alving, Kjell; Hallgren, Jenny

    2016-01-28

    Mast cells are rare tissue-resident immune cells that are involved in allergic reactions, and their numbers are increased in the lungs of asthmatics. Murine lung mast cells arise from committed bone marrow-derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in the tissue. In humans, mast cells can be cultured from multipotent CD34(+) progenitor cells. However, a population of distinct precursor cells that give rise to mast cells has remained undiscovered. To our knowledge, this is the first report of human lineage-negative (Lin(-)) CD34(hi) CD117(int/hi) FcεRI(+) progenitor cells, which represented only 0.0053% of the isolated blood cells in healthy individuals. These cells expressed integrin β7 and developed a mast cell-like phenotype, although with a slow cell division capacity in vitro. Isolated Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells had an immature mast cell-like appearance and expressed high levels of many mast cell-related genes as compared with human blood basophils in whole-transcriptome microarray analyses. Furthermore, serglycin, tryptase, and carboxypeptidase A messenger RNA transcripts were detected by quantitative reverse transcription-polymerase chain reaction. Altogether, we propose that the Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells are closely related to human tissue mast cells and likely constitute an immediate precursor population, which can give rise to predominantly mast cells. Furthermore, asthmatics with reduced lung function had a higher frequency of Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood mast cell progenitors than asthmatics with normal lung function.

  16. Effect of heparin addition on expansion of cord blood hematopoietic progenitor cells in three-dimensional coculture with stromal cells in nonwoven fabrics.

    Science.gov (United States)

    Okamoto, Toru; Takagi, Mutsumi; Soma, Toshihiro; Ogawa, Hiroyasu; Kawakami, Manabu; Mukubo, Masaaki; Kubo, Kazusuke; Sato, Reiko; Toma, Kazunori; Yoshida, Toshiomi

    2004-01-01

    Primary human cord blood mononuclear cells (CB MNCs) were inoculated into layers of primary human bone marrow stromal cells prepared in a nonwoven fabric porous carrier [three dimensional (3-D)] or on a dish [two dimensional (2-D)] using a cytokine-free medium and were cultured for 7 days with or without the addition of heparin. The number of progenitor cells increased threefold during the 3-D coculture, whereas it decreased in the 2-D culture. Heparin addition to the 3-D coculture further increased the number of progenitors twofold, whereas the addition of desulfated heparin had no effect. The heparin effect was also observed in a 3-D culture of CB MNCs without stromal cells when conditioned medium was employed. The coating of the carrier with N-(O-beta-(6-O-sulfogalactopyranosyl)-6-oxyhexyl)-3,5-bis (dodecyloxy)-benzamide instead of heparin addition also increased the number of progenitor cells in the 3-D culture of CB MNCs without stromal cells when the conditioned medium was employed. The 3-D coculture constructed with nonwoven fabrics and stromal cells was clearly superior to the 2-D culture because of the expansion of CB hematopoietic progenitor cells without cytokine addition. Heparin addition to the 3-D coculture further increased the number of progenitor cells, which may result from a synergistic effect of soluble cytokines produced by stromal cells with the sulfur group of heparin. PMID:15739052

  17. bantam miRNA is important for Drosophila blood cell homeostasis and a regulator of proliferation in the hematopoietic progenitor niche

    Energy Technology Data Exchange (ETDEWEB)

    Lam, Victoria; Tokusumi, Tsuyoshi; Tokusumi, Yumiko; Schulz, Robert A., E-mail: rschulz@nd.edu

    2014-10-24

    Highlights: • bantam miRNA is endogenously expressed in the hematopoietic progenitor niche. • bantam is necessary and sufficient to induce cellular proliferation in the PSC. • bantam is upstream of the Insulin Receptor signaling pathway. • A model for positive regulation of hematopoietic niche growth is proposed. - Abstract: The Drosophila hematopoietic system is utilized in this study to gain novel insights into the process of growth control of the hematopoietic progenitor niche in blood development. The niche microenvironment is an essential component controlling the balance between progenitor populations and differentiated, mature blood cells and has been shown to lead to hematopoietic malignancies in humans when misregulated. MicroRNAs are one class of regulators associated with blood malignancies; however, there remains a relative paucity of information about the role of miRNAs in the niche. Here we demonstrate that bantam miRNA is endogenously active in the Drosophila hematopoietic progenitor niche, the posterior signaling center (PSC), and functions in the primary hematopoietic organ, the lymph gland, as a positive regulator of growth. Loss of bantam leads to a significant reduction in the PSC and overall lymph gland size, as well as a loss of the progenitor population and correlative premature differentiation of mature hemocytes. Interestingly, in addition to being essential for proper lymph gland development, we have determined bantam to be a novel upstream component of the insulin signaling cascade in the PSC and have unveiled dMyc as one factor central to bantam activity. These important findings identify bantam as a new hematopoietic regulator, place it in an evolutionarily conserved signaling pathway, present one way in which it is regulated, and provide a mechanism through which it facilitates cellular proliferation in the hematopoietic niche.

  18. bantam miRNA is important for Drosophila blood cell homeostasis and a regulator of proliferation in the hematopoietic progenitor niche

    International Nuclear Information System (INIS)

    Highlights: • bantam miRNA is endogenously expressed in the hematopoietic progenitor niche. • bantam is necessary and sufficient to induce cellular proliferation in the PSC. • bantam is upstream of the Insulin Receptor signaling pathway. • A model for positive regulation of hematopoietic niche growth is proposed. - Abstract: The Drosophila hematopoietic system is utilized in this study to gain novel insights into the process of growth control of the hematopoietic progenitor niche in blood development. The niche microenvironment is an essential component controlling the balance between progenitor populations and differentiated, mature blood cells and has been shown to lead to hematopoietic malignancies in humans when misregulated. MicroRNAs are one class of regulators associated with blood malignancies; however, there remains a relative paucity of information about the role of miRNAs in the niche. Here we demonstrate that bantam miRNA is endogenously active in the Drosophila hematopoietic progenitor niche, the posterior signaling center (PSC), and functions in the primary hematopoietic organ, the lymph gland, as a positive regulator of growth. Loss of bantam leads to a significant reduction in the PSC and overall lymph gland size, as well as a loss of the progenitor population and correlative premature differentiation of mature hemocytes. Interestingly, in addition to being essential for proper lymph gland development, we have determined bantam to be a novel upstream component of the insulin signaling cascade in the PSC and have unveiled dMyc as one factor central to bantam activity. These important findings identify bantam as a new hematopoietic regulator, place it in an evolutionarily conserved signaling pathway, present one way in which it is regulated, and provide a mechanism through which it facilitates cellular proliferation in the hematopoietic niche

  19. The proteoglycan Trol controls the architecture of the extracellular matrix and balances proliferation and differentiation of blood progenitors in the Drosophila lymph gland.

    Science.gov (United States)

    Grigorian, Melina; Liu, Ting; Banerjee, Utpal; Hartenstein, Volker

    2013-12-15

    The heparin sulfate proteoglycan Terribly Reduced Optic Lobes (Trol) is the Drosophila melanogaster homolog of the vertebrate protein Perlecan. Trol is expressed as part of the extracellular matrix (ECM) found in the hematopoietic organ, called the lymph gland. In the normal lymph gland, the ECM forms thin basement membranes around individual or small groups of blood progenitors. The pattern of basement membranes, reported by Trol expression, is spatio-temporally correlated to hematopoiesis. The central, medullary zone which contain undifferentiated hematopoietic progenitors has many, closely spaced membranes. Fewer basement membranes are present in the outer, cortical zone, where differentiation of blood cells takes place. Loss of trol causes a dramatic change of the ECM into a three-dimensional, spongy mass that fills wide spaces scattered throughout the lymph gland. At the same time proliferation is reduced, leading to a significantly smaller lymph gland. Interestingly, differentiation of blood progenitors in trol mutants is precocious, resulting in the break-down of the usual zonation of the lymph gland. which normally consists of an immature center (medullary zone) where cells remain undifferentiated, and an outer cortical zone, where differentiation sets in. We present evidence that the effect of Trol on blood cell differentiation is mediated by Hedgehog (Hh) signaling, which is known to be required to maintain an immature medullary zone. Overexpression of hh in the background of a trol mutation is able to rescue the premature differentiation phenotype. Our data provide novel insight into the role of the ECM component Perlecan during Drosophila hematopoiesis. PMID:23510717

  20. High dose ionizing irradiation induces an early and transient increase in peripheral blood hematopoietic progenitor cells; L`exposition aigue aux radiations ionisantes induit un recrutement transitoire des progeniteurs hematopoietiques au niveau du sang peripherique: implications therapeutiques potentielles

    Energy Technology Data Exchange (ETDEWEB)

    Drouet, M.; Mathieu, J.; Grenier, N.; Vetillard, J.; Chauvelot, F.; Thierry, D.; Mestries, J.C.; Herodin, F. [Centre de Recherches du Service de Sante des Armees, La Tronche, 38 - Grenoble (France)]|[Centre de Recherches du Service de Sante des Armees - Centre d`Etudes Nucleaires de Fontenay-aux-Roses, 92 (France)

    1997-12-31

    Nonhuman primates exposed to ionizing radiation exhibit an early and transient increase in peripheral blood committed hematopoietic progenitor cells. The management of bone marrow aplasia secondary to accidental irradiation could be based in part on the re-infusion of those circulating autologous progenitors following a period of ex vivo expansion with cytokines. (authors)

  1. Transforming human blood stem and progenitor cells: A new way forward in leukemia modeling

    OpenAIRE

    Mulloy, James C.; Wunderlich, Mark; Zheng, Yi; Wei, Junping

    2008-01-01

    MLL-AF9 (MA9) is a leukemia fusion gene formed upon translocation of the AF9 gene on chromosome 9 and the MLL gene on chromosome 11. MA9 is commonly found in acute myeloid leukemia (AML) and occasionally in acute lymphoid leukemia and is associated with intermediate to poor outcome. The specific signaling pathways downstream of MA9 are still poorly understood. We have recently described a model system whereby we expressed the MA9 fusion gene in human CD34+ Umbilical Cord Blood (UCB) cells and...

  2. Neuroprotective Effects of Transplanted Mesenchymal Stromal Cells-derived Human Umbilical Cord Blood Neural Progenitor Cells in EAE

    Directory of Open Access Journals (Sweden)

    Hassan Rafieemehr

    2015-11-01

    Full Text Available Multiple Sclerosis (MS is an autoimmune inflammatory demyelinating disease of the central nervous system. The aim of this study was to investigate the neuroprotective effects of transplanted human umbilical cord blood mesenchymal stromal cells (UCB-MSC derived neural progenitor cell (MDNPC in EAE, an experimental model of MS. To initiate neuronal differentiation of UCB-MSCs, the pre-induction medium was removed and replaced with induction media containing retinoic acid, b FGF, h EGF, NGF, IBMX and ascorbic acid for one week. The expression of neural genes was examined in comparison to control group by real-time PCR assay. Then, experimental autoimmune encephalitis (EAE was induced using myelin oligodendrocyte glycoprotein (MOG, 35-55 peptides in 24 C57BL/6 mice. After induction, the mice were divided in four groups (n=6 as follows: healthy, PBS, UCB-MSCs and MDNPC, respectively. At the end of the study, disease status in all the groups was analyzed using hematoxylin-eosin (H&E staining of brain sections. We found that UCB-MSCs exhibit neuronal differentiation potential in vitro and transplanted MDNPC lowered clinical score and reduced CNS leukocyte infiltration compared to untreated mice. Our results showed that MDNPC from UCB may be a proper candidate for regenerative therapy in MS and other neurodegenerative diseases. 

  3. The effects of smoking on levels of endothelial progenitor cells and microparticles in the blood of healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Fariborz Mobarrez

    Full Text Available BACKGROUND: Cigarette smoking, both active and passive, is one of the leading causes of morbidity and mortality in cardiovascular disease. To assess the impact of brief smoking on the vasculature, we determined levels of circulating endothelial progenitor cells (EPCs and circulating microparticles (MPs following the smoking of one cigarette by young, healthy intermittent smokers. MATERIALS AND METHODS: 12 healthy volunteers were randomized to either smoking or not smoking in a crossover fashion. Blood sampling was performed at baseline, 1, 4 and 24 hours following smoking/not smoking. The numbers of EPCs and MPs were determined by flow cytometry. MPs were measured from platelets, leukocytes and endothelial cells. Moreover, MPs were also labelled with anti-HMGB1 and SYTO 13 to assess the content of nuclear molecules. RESULTS: Active smoking of one cigarette caused an immediate and significant increase in the numbers of circulating EPCs and MPs of platelet-, endothelial- and leukocyte origin. Levels of MPs containing nuclear molecules were increased, of which the majority were positive for CD41 and CD45 (platelet- and leukocyte origin. CD144 (VE-cadherin or HMGB1 release did not significantly change during active smoking. CONCLUSION: Brief active smoking of one cigarette generated an acute release of EPC and MPs, of which the latter contained nuclear matter. Together, these results demonstrate acute effects of cigarette smoke on endothelial, platelet and leukocyte function as well as injury to the vascular wall.

  4. Clinical-scale cultures of cord blood CD34(+) cells to amplify committed progenitors and maintain stem cell activity.

    Science.gov (United States)

    Ivanovic, Zoran; Duchez, Pascale; Chevaleyre, Jean; Vlaski, Marija; Lafarge, Xavier; Dazey, Bernard; Robert-Richard, Elodie; Mazurier, Frédéric; Boiron, Jean-Michel

    2011-01-01

    We developed a clinical-scale cord blood (CB) cell ex vivo procedure to enable an extensive expansion of committed progenitors--colony-forming cells (CFCs) without impairing very primitive hematopoietic stem cells (HSCs). CD34(++) cells, selected from previously cryopreserved and thawed CB units, were cultured in two steps (diluted 1:4 after 6 days) in the presence of stem cell factor (SCF), fms-related tyrosine kinase 3 ligand (Flt-3L), megakaryocyte growth and development factor (MGDF) (100 ng/ml each), granulocyte-colony stimulating factor (G-CSF) (10 ng/ml) in HP01 serum-free medium. HSC activity was evaluated in a serial transplantation assay, by detection of human cells (CD45, CD33, CD19 and CFC of human origin) in bone marrow (BM) of primary and secondary recipient NOD/SCID mice 6-8 weeks after transplantation. A wide amplification of total cells (∼350-fold), CD34(+) cells (∼100-fold), and CFC (∼130-fold) without impairing the HSC activity was obtained. The activity of a particular HSC subpopulation (SRC(CFC)) was even enhanced.Thus, an extensive ex vivo expansion of CFCs is feasible without impairing the activity of HSCs. This result was enabled by associating antioxidant power of medium with an appropriate cytokine cocktail (i.e., mimicking physiologic effects of a weak oxygenation in hematopoietic environment).

  5. Comparison of Fibronectin and Collagen in Supporting the Isolation and Expansion of Endothelial Progenitor Cells from Human Adult Peripheral Blood.

    Directory of Open Access Journals (Sweden)

    Elena Colombo

    Full Text Available Endothelial colony-forming cells (ECFCs, are circulating endothelial progenitor cells increasingly studied in various diseases because of their potential for clinical translation. Experimental procedures for their ex vivo culture still lack standardization. In particular two different extracellular matrix proteins, either fibronectin or collagen, are commonly used by different Authors for coating plastic plates, both allowing to obtain cells that have all the features of ECFCs. However, possible differences in the impact of each substrate on ECFCs have not been analysed, so far. Therefore, in this study we investigated whether fibronectin and collagen may differentially affect ECFC cultures.ECFCs were isolated and cultured from peripheral blood mononuclear cells of healthy donors. The impact of fibronectin compared with collagen as the only variable of the experimental procedure was analysed separately in the phase of isolation of ECFC colonies and in the following phase of cell expansion. In the isolation phase, although similar frequencies of colonies were obtained on the two substrates, ECFC colonies appeared some days earlier when mononuclear cells were seeded on fibronectin rather than collagen. In the expansion phase, ECFCs cultured on collagen showed a longer lifespan and higher cell yields compared with ECFCs cultured on fibronectin, possibly related to the higher levels of IL-6 and IL-8 measured in their supernatants. ECFCs cultured on both substrates showed similar immunophenotype and ability for in vitro tube formation.Overall, the results of this study indicate that, although both fibronectin and collagen efficiently sustain ECFC cultures, each of them brings some advantages within individual steps of the entire process. We suggest that colony isolation performed on fibronectin followed by cell expansion performed on collagen may represent a novel and the most efficient strategy to obtain ECFCs from adult peripheral blood samples.

  6. Influence of Rho Kinase Inhibitor Fasudil on Late Endothelial Progenitor Cells in Peripheral Blood of COPD Patients with Pulmonary Artery Hypertension

    OpenAIRE

    Liu, Pei; Zhang, Hongmei; Tang, Yijun; Sheng, Chunfeng; Liu, Jianxin; Zeng, Yanjun

    2014-01-01

    The objective of our work was to investigate the influence of Fasudil, a Rho inhibitor on the number and function of the late endothelial progenitor cells in peripheral blood of chronic obstructive pulmonary diseases (COPD) patients with pulmonary artery hypertension. Eighty COPD patients with pulmonary artery hypertension were selected and divided into two groups: the treatment group and the control group, which had 40 patients respectively. The control group received routine treatment, incl...

  7. Polycomb Cbx family members mediate the balance between haematopoietic stem cell self-renewal and differentiation.

    Science.gov (United States)

    Klauke, Karin; Radulović, Višnja; Broekhuis, Mathilde; Weersing, Ellen; Zwart, Erik; Olthof, Sandra; Ritsema, Martha; Bruggeman, Sophia; Wu, Xudong; Helin, Kristian; Bystrykh, Leonid; de Haan, Gerald

    2013-04-01

    The balance between self-renewal and differentiation of adult stem cells is essential for tissue homeostasis. Here we show that in the haematopoietic system this process is governed by polycomb chromobox (Cbx) proteins. Cbx7 is specifically expressed in haematopoietic stem cells (HSCs), and its overexpression enhances self-renewal and induces leukaemia. This effect is dependent on integration into polycomb repressive complex-1 (PRC1) and requires H3K27me3 binding. In contrast, overexpression of Cbx2, Cbx4 or Cbx8 results in differentiation and exhaustion of HSCs. ChIP-sequencing analysis shows that Cbx7 and Cbx8 share most of their targets; we identified approximately 200 differential targets. Whereas genes targeted by Cbx8 are highly expressed in HSCs and become repressed in progenitors, Cbx7 targets show the opposite expression pattern. Thus, Cbx7 preserves HSC self-renewal by repressing progenitor-specific genes. Taken together, the presence of distinct Cbx proteins confers target selectivity to PRC1 and provides a molecular balance between self-renewal and differentiation of HSCs.

  8. High-resolution imaging and computational analysis of haematopoietic cell dynamics in vivo.

    Science.gov (United States)

    Koechlein, Claire S; Harris, Jeffrey R; Lee, Timothy K; Weeks, Joi; Fox, Raymond G; Zimdahl, Bryan; Ito, Takahiro; Blevins, Allen; Jung, Seung-Hye; Chute, John P; Chourasia, Amit; Covert, Markus W; Reya, Tannishtha

    2016-01-01

    Although we know a great deal about the phenotype and function of haematopoietic stem/progenitor cells, a major challenge has been mapping their dynamic behaviour within living systems. Here we describe a strategy to image cells in vivo with high spatial and temporal resolution, and quantify their interactions using a high-throughput computational approach. Using these tools, and a new Msi2 reporter model, we show that haematopoietic stem/progenitor cells display preferential spatial affinity for contacting the vascular niche, and a temporal affinity for making stable associations with these cells. These preferences are markedly diminished as cells mature, suggesting that programs that control differentiation state are key determinants of spatiotemporal behaviour, and thus dictate the signals a cell receives from specific microenvironmental domains. These collectively demonstrate that high-resolution imaging coupled with computational analysis can provide new biological insight, and may in the long term enable creation of a dynamic atlas of cells within their native microenvironment. PMID:27425143

  9. Effects of aspirin on number,activity and inducible nitric oxide synthase of endothelial progenitor cells from peripheral blood

    Institute of Scientific and Technical Information of China (English)

    Tu-gang CHEN; Jun-zhu CHEN; Xu-dong XIE

    2006-01-01

    Aim:To investigate whether aspirin has an influence on endothelial progenitor cells (EPC).Methods:Total mononuclear cells (MNC) were isolated from peripheral blood by Ficoll density gradient centrifugation,then cells were plated on fibronectin-coated culture dishes.After 7 d of culture,attached cells were stimulated with aspirin (to achieve final concentrations of 1,2,5,and 10 mmol/L) for 3,6,12,and 24 h.EPC were characterized as adherent cells that were double positive for 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine low density lipoprotein (DiLDL) uptake and lectin binding by direct fluorescent staining.EPC proliferation and migration were assayed using a 3- (4,5-dimethyl-2 thiazoyl) -2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and a modified Boyden chamber assay.respectively.An EPC adhesion assay was performed by replating the EPC on fibronectin-coated dishes,and then adherent cells were counted.In vitro vasculogenesis activity was assayed by using an in vitro vasculogenesis kit. Inducible nitric oxide synthase (iNOS) was assayed by Westem blotting.Results:Incubation of isolated human MNC with aspirin decreased the number of EPC.Aspirin also decreased the proliferative,migratory,adhesive,and in vitro Vasculogenesis capacity of EPC,and also their iNOS levels in a concentration-and time-dependent manner.Conclusion:Aspirin decreases (1) the number of EPC; (2) the proliferative,migratory,adhesive and in vitro vasculogenesis capacities of EPC;and (3) iNOS levels in EPC.

  10. Human cord blood progenitors with high aldehyde dehydrogenase activity improve vascular density in a model of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Creer Michael H

    2010-03-01

    Full Text Available Abstract Human stem cells from adult sources have been shown to contribute to the regeneration of muscle, liver, heart, and vasculature. The mechanisms by which this is accomplished are, however, still not well understood. We tested the engraftment and regenerative potential of human umbilical cord blood-derived ALDHhiLin-, and ALDHloLin- cells following transplantation to NOD/SCID or NOD/SCID β2m null mice with experimentally induced acute myocardial infarction. We used combined nanoparticle labeling and whole organ fluorescent imaging to detect human cells in multiple organs 48 hours post transplantation. Engraftment and regenerative effects of cell treatment were assessed four weeks post transplantation. We found that ALDHhiLin- stem cells specifically located to the site of injury 48 hours post transplantation and engrafted the infarcted heart at higher frequencies than ALDHloLin- committed progenitor cells four weeks post transplantation. We found no donor derived cardiomyocytes and few endothelial cells of donor origin. Cell treatment was not associated with any detectable functional improvement at the four week endpoint. There was, however, a significant increase in vascular density in the central infarct zone of ALDHhiLin- cell-treated mice, as compared to PBS and ALDHloLin- cell-treated mice. Conclusions Our data indicate that adult human stem cells do not become a significant part of the regenerating tissue, but rapidly home to and persist only temporarily at the site of hypoxic injury to exert trophic effects on tissue repair thereby enhancing vascular recovery.

  11. Development of a xeno-free autologous culture system for endothelial progenitor cells derived from human umbilical cord blood.

    Directory of Open Access Journals (Sweden)

    Sung-Hwan Moon

    Full Text Available Despite promising preclinical outcomes in animal models, a number of challenges remain for human clinical use. In particular, expanding a large number of endothelial progenitor cells (EPCs in vitro in the absence of animal-derived products is the most critical hurdle remaining to be overcome to ensure the safety and efficiency of human therapy. To develop in vitro culture conditions for EPCs derived from human cord blood (hCB-EPCs, we isolated extracts (UCE and collagen (UC-collagen from umbilical cord tissue to replace their animal-derived counterparts. UC-collagen and UCE efficiently supported the attachment and proliferation of hCB-EPCs in a manner comparable to that of animal-derived collagen in the conventional culture system. Our developed autologous culture system maintained the typical characteristics of hCB-EPCs, as represented by the expression of EPC-associated surface markers. In addition, the therapeutic potential of hCB-EPCs was confirmed when the transplantation of hCB-EPCs cultured in this autologous culture system promoted limb salvage in a mouse model of hindlimb ischemia and was shown to contribute to attenuating muscle degeneration and fibrosis. We suggest that the umbilical cord represents a source for autologous biomaterials for the in vitro culture of hCB-EPCs. The main characteristics and therapeutic potential of hCB-EPCs were not compromised in developed autologous culture system. The absence of animal-derived products in our newly developed in vitro culture removes concerns associated with secondary contamination. Thus, we hope that this culture system accelerates the realization of therapeutic applications of autologous hCB-EPCs for human vascular diseases.

  12. The influence of gender- and age-related differences in the radiosensitivity of hematopoietic progenitor cells detected in steady-state human peripheral blood

    International Nuclear Information System (INIS)

    To investigate the importance of gender and aging on the individual radiosensitivity of lineage-committed myeloid hematopoietic stem/progenitor cells (HSPCs) detected in mononuclear cells (MNCs) of steady-state human peripheral blood (PB), the clonogenic survival of HPCs, including colony-forming unit-granulocyte macrophage; burst-forming unit-erythroid; colony-forming unit-granulocyte-erythroid-macrophage-megakaryocyte cells derived from MNCs exposed to 0.5 Gy and 2 Gy X-irradiation were estimated. MNCs were prepared from the buffy-coats of 59 healthy individual blood donors. The results showed that large individual differences exist in the number of HSPCs, as well as in the surviving fraction of cells. Furthermore, the number of progenitor cells strongly correlated with their surviving fraction, suggesting that the radiosensitivity of hematopoietic progenitor cells decreases with the number of cells in the 105 cells population. A statistically significant negative correlation was observed between the surviving fraction observed at a dose of 0.5 Gy and the age of an individual, however, none of these correlations were observed after 2 Gy irradiation. No statistically significant difference was observed in individual radiosensitivity between males and females at either radiation dose. The present results indicated a correlation between the individual responsiveness of HSPCs to ionizing irradiation, especially to low dose irradiation, and aging. (author)

  13. A defined, feeder-free, serum-free system to generate in vitro hematopoietic progenitors and differentiated blood cells from hESCs and hiPSCs.

    Directory of Open Access Journals (Sweden)

    Giorgia Salvagiotto

    Full Text Available Human ESC and iPSC are an attractive source of cells of high quantity and purity to be used to elucidate early human development processes, for drug discovery, and in clinical cell therapy applications. To efficiently differentiate pluripotent cells into a pure population of hematopoietic progenitors we have developed a new 2-dimensional, defined and highly efficient protocol that avoids the use of feeder cells, serum or embryoid body formation. Here we showed that a single matrix protein in combination with growth factors and a hypoxic environment is sufficient to generate from pluripotent cells hematopoietic progenitors capable of differentiating further in mature cell types of different lineages of the blood system. We tested the differentiation method using hESCs and 9 iPSC lines generated from different tissues. These data indicate the robustness of the protocol providing a valuable tool for the generation of clinical-grade hematopoietic cells from pluripotent cells.

  14. Radioprotective potency of ginseng on some haematopoietic and physiological parameters in irradiated rats

    International Nuclear Information System (INIS)

    Currently, investigations focus on co administration of natural products with radiation treatment. The present study was assessed to investigate the potency of ginseng as a radioprotective agent on haematopoietic cell recovery, the content of reduced glutathione (GSH) and malonaldehyde (MDA) level in addition to physiological bio markers. Panax ginseng was intraperitoneally injected (100 mg/ kg) to female rats 24 h before gamma irradiation of 7 Gy which is liable to disturb the haematopoietic system and the organs involved as the bone marrow and spleen. Animals were investigated after 5 and 9 days from irradiation, ginseng or dual treatments. Irradiation caused significant wt loss of the body and spleen, decrease in bone marrow (B.M.) viable cells, significant depression in leukocytes with its differential counts, significant drop in erythrocytes, haemoglobin and haematocrite values besides elevation in MCV. Gamma-irradiation treatment resulted in significant increase in serum MDA and glucose as well as significant reduction in blood GSH. Significant elevations in transaminases (ALT and AST) and alkaline phosphatase (ALP) activities were recorded after gamma irradiation. Preservation of body wt, B.M. viable cells, spleen wt and haematopoietic cell recovery was evident upon ginseng pre-administration. It ameliorated the depression in GSH content and the elevation in MDA level. ALT, AST and ALP were depressed approaching the control level after 9 days from dual treatments and blood sugar level was maintained. The study points out the promising positive role played by ginseng as a nontoxic natural product to reduce the time necessary for reconstituting haematopoietic cells and protecting vital physiological processes after irradiation

  15. Grain and bean lysates improve function of endothelial progenitor cells from human peripheral blood: involvement of the endogenous antioxidant defenses.

    Directory of Open Access Journals (Sweden)

    Daniela Lucchesi

    Full Text Available Increased oxidative stress contributes to the functional impairment of endothelial progenitor cells (EPCs, the pivotal players in the servicing of the endothelial cell lining. Several evidences suggest that decreasing oxidative stress by natural compounds with antioxidant properties may improve EPCs bioactivity. Here, we investigated the effects of Lisosan G (LG, a Triticum Sativum grain powder, and Lady Joy (LJ, a bean lysate, on function of EPCs exposed to oxidative stress. Peripheral blood mononuclear cells were isolated and plated on fibronectin-coated culture dishes; adherent cells, identified as early EPCs, were pre-treated with different concentrations of LG and LJ and incubated with hydrogen peroxide (H2O2. Viability, senescence, adhesion, ROS production and antioxidant enzymes gene expression were evaluated. Lysate-mediated Nrf-2 (nuclear factor (erythroid-derived 2-like 2/ARE (antioxidant response element activation, a modulator of oxidative stress, was assessed by immunocytochemistry. Lady Joy 0.35-0.7 mg/ml increases EPCs viability; pre-treatment with either LG 0.7 mg/ml and LJ 0.35-0.7 mg/ml protect EPCs viability against H2O2-induced injury. LG 0.7 and LJ 0.35-0.7 mg/ml improve EPCs adhesion; pre-treatment with either LG 0.35 and 0.7 mg/ml or LJ 0.35, 0.7 and 1.4 mg/ml preserve adhesiveness of EPCs exposed to H2O2. Senescence is attenuated in EPCs incubated with lysates 0.35 mg/ml. After exposure to H2O2, LG pre-treated cells show a lower senescence than untreated EPCs. Lysates significantly decrease H2O2-induced ROS generation. Both lysates increase glutathione peroxidase-1 and superoxide dismutase-2 (SOD-2 expression; upon H2O2 exposure, pre-treatment with LJ allows higher SOD-2 expression. Heme oxigenase-1 increases in EPCs pre-treated with LG even upon H2O2 exposure. Finally, incubation with LG 0.7 mg/ml results in Nrf-2 translocation into the nucleus both at baseline and after the oxidative challenge. Our data suggest a

  16. Imaging in haematopoietic stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Evans, A.; Steward, C.G.; Lyburn, I.D.; Grier, D.J

    2003-03-01

    Haematopoietic stem cell transplantation (SCT) is used to treat a wide range of malignant and non-malignant haematological conditions, solid malignancies, and metabolic and autoimmune diseases. Although imaging has a limited role before SCT, it is important after transplantation when it may support the clinical diagnosis of a variety of complications. It may also be used to monitor the effect of therapy and to detect recurrence of the underlying disease if the transplant is unsuccessful. We present a pictorial review of the imaging of patients who have undergone SCT, based upon 15 years experience in a large unit performing both adult and paediatric transplants.

  17. Involvement of placental/umbilical cord blood acid–base status and gas values on the radiosensitivity of human fetal/neonatal hematopoietic stem/progenitor cells

    OpenAIRE

    Yamaguchi, Masaru; EBINA, SATOKO; Kashiwakura, Ikuo

    2012-01-01

    Arterial cord blood (CB) acid–base status and gas values, such as pH, PCO2, PO2, HCO3 −and base excess, provide useful information on the fetal and neonatal condition. However, it remains unknown whether these values affect the radiosensitivity of fetal/neonatal hematopoiesis. The present study evaluated the relationship between arterial CB acid–base status, gas values, and the radiosensitivity of CB hematopoietic stem/progenitor cells (HSPCs). A total of 25 CB units were collected. The arter...

  18. Distinct Sources of Hematopoietic Progenitors Emerge before HSCs and Provide Functional Blood Cells in the Mammalian Embryo

    Directory of Open Access Journals (Sweden)

    Kathleen E. McGrath

    2015-06-01

    Full Text Available Hematopoietic potential arises in mammalian embryos before adult-repopulating hematopoietic stem cells (HSCs. At embryonic day 9.5 (E9.5, we show the first murine definitive erythro-myeloid progenitors (EMPs have an immunophenotype distinct from primitive hematopoietic progenitors, maturing megakaryocytes and macrophages, and rare B cell potential. EMPs emerge in the yolk sac with erythroid and broad myeloid, but not lymphoid, potential. EMPs migrate to the fetal liver and rapidly differentiate, including production of circulating neutrophils by E11.5. Although the surface markers, transcription factors, and lineage potential associated with EMPs overlap with those found in adult definitive hematopoiesis, they are present in unique combinations or proportions that result in a specialized definitive embryonic progenitor. Furthermore, we find that embryonic stem cell (ESC-derived hematopoiesis recapitulates early yolk sac hematopoiesis, including primitive, EMP, and rare B cell potential. EMPs do not have long-term potential when transplanted in immunocompromised adults, but they can provide transient adult-like RBC reconstitution.

  19. Haematopoietic cell transplants in Latin America.

    Science.gov (United States)

    Gale, R P; Seber, A; Bonfim, C; Pasquini, M

    2016-07-01

    Haematopoietic cell transplants are done by more than 1500 transplant centres in 75 countries, mostly for life-threatening haematological disorders. However, transplant technology and access are not uniformly distributed worldwide. Most transplants are done predominately in Europe, North America and some Asian countries. We review transplant activity in Latin America, a geographic region with a population of >600 million persons living in countries with diverse economic and social development levels. These data indicate a 20-40-fold lower frequency of transplants in Latin America compared with Europe and North America. We show that although economics, infrastructure and expertise are important limitations, other variables also operate. Changes in several of these variables may substantially increase transplant activity in Latin America. PMID:26999468

  20. Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy

    NARCIS (Netherlands)

    Halter, Joerg P.; Schuepbach, W. Michael M.; Mandel, Hanna; Casali, Carlo; Orchard, Kim; Collin, Matthew; Valcarcel, David; Rovelli, Attilio; Filosto, Massimiliano; Dotti, Maria T.; Marotta, Giuseppe; Pintos, Guillem; Barba, Pere; Accarino, Anna; Ferra, Christelle; Illa, Isabel; Beguin, Yves; Bakker, Jaap A.; Boelens, Jaap J.; de Coo, Irenaeus F. M.; Fay, Keith; Sue, Carolyn M.; Nachbaur, David; Zoller, Heinz; Sobreira, Claudia; Simoes, Belinda Pinto; Hammans, Simon R.; Savage, David; Marti, Ramon; Chinnery, Patrick F.; Elhasid, Ronit; Gratwohl, Alois; Hirano, Michio

    2015-01-01

    Haematopoietic stem cell transplantation has been proposed as treatment for mitochondrial neurogastrointestinal encephalomyopathy, a rare fatal autosomal recessive disease due to TYMP mutations that result in thymidine phosphorylase deficiency. We conducted a retrospective analysis of all known pati

  1. Eurocord position on ethical and legal issues involved in cord blood transplantation.

    Science.gov (United States)

    Fernandez, M N

    1998-07-01

    The Eurocord group held a round table discussion on the topic of ethical and legal issues involved in cord blood transplantation at the group's 2nd annual meeting at Annecy in May 1997. As chairman of the session the author was commissioned to put in writing the group's consensus on the subject. This covers the topics of: cord blood collections for autologous and intra-familiar usage; procreation for the purpose of haematopoietic progenitor cell donation for transplantation of a family member; cord blood banking including safety requirements and quality control regulations; patient priorities for usage of stored units; and patent rights. This paper's text was submitted for review to other participating members of the group. No amendments were made. The author feels confident that the paper faithfully reflects the consensus achieved. PMID:9715901

  2. Cord Blood-Derived Hematopoietic Stem/Progenitor Cells: Current Challenges in Engraftment, Infection, and Ex Vivo Expansion

    OpenAIRE

    Katsuhiro Kita; Lee, Jong O; Finnerty, Celeste C.; Herndon, David N

    2011-01-01

    Umbilical cord blood has served as an alternative to bone marrow for hematopoietic transplantation since the late 1980s. Numerous clinical studies have proven the efficacy of umbilical cord blood. Moreover, the possible immaturity of cells in umbilical cord blood gives more options to recipients with HLA mismatch and allows for the use of umbilical cord blood from unrelated donors. However, morbidity and mortality rates associated with hematopoietic malignancies still remain relatively high, ...

  3. Cord Blood-Derived Hematopoietic Stem/Progenitor Cells: Current Challenges in Engraftment, Infection, and Ex Vivo Expansion

    Directory of Open Access Journals (Sweden)

    Katsuhiro Kita

    2011-01-01

    Full Text Available Umbilical cord blood has served as an alternative to bone marrow for hematopoietic transplantation since the late 1980s. Numerous clinical studies have proven the efficacy of umbilical cord blood. Moreover, the possible immaturity of cells in umbilical cord blood gives more options to recipients with HLA mismatch and allows for the use of umbilical cord blood from unrelated donors. However, morbidity and mortality rates associated with hematopoietic malignancies still remain relatively high, even after cord blood transplantation. Infections and relapse are the major causes of death after cord blood transplantation in patients with hematopoietic diseases. Recently, new strategies have been introduced to improve these major problems. Establishing better protocols for simple isolation of primitive cells and ex vivo expansion will also be very important. In this short review, we discuss several recent promising findings related to the technical improvement of cord blood transplantation.

  4. Cord Blood-Derived Hematopoietic Stem/Progenitor Cells: Current Challenges in Engraftment, Infection, and Ex Vivo Expansion

    Science.gov (United States)

    Kita, Katsuhiro; Lee, Jong O.; Finnerty, Celeste C.; Herndon, David N.

    2011-01-01

    Umbilical cord blood has served as an alternative to bone marrow for hematopoietic transplantation since the late 1980s. Numerous clinical studies have proven the efficacy of umbilical cord blood. Moreover, the possible immaturity of cells in umbilical cord blood gives more options to recipients with HLA mismatch and allows for the use of umbilical cord blood from unrelated donors. However, morbidity and mortality rates associated with hematopoietic malignancies still remain relatively high, even after cord blood transplantation. Infections and relapse are the major causes of death after cord blood transplantation in patients with hematopoietic diseases. Recently, new strategies have been introduced to improve these major problems. Establishing better protocols for simple isolation of primitive cells and ex vivo expansion will also be very important. In this short review, we discuss several recent promising findings related to the technical improvement of cord blood transplantation. PMID:21603139

  5. Low O2 concentrations enhance the positive effect of IL-17 on the maintenance of erythroid progenitors during co-culture of CD34+ and mesenchymal stem cells.

    Science.gov (United States)

    Krstić, Aleksandra; Vlaski, Marija; Hammoud, Mohammad; Chevaleyre, Jean; Duchez, Pascale; Jovcić, Gordana; Bugarski, Diana; Milenković, Pavle; Bourin, Philippe; Boiron, Jean-Michel; Praloran, Vincent; Ivanović, Zoran

    2009-03-01

    Co-culture of haematopoietic cells with a stromal cell layer does not mimic the physiological, micro-environmental niche, whose major feature is a low oxygen (O2) concentration. Thus, in order to study the effects of IL-17 in a context which better approximates the physiological state, we investigated its effects on cell expansion, colony-forming ability, and the phenotypical profile of normal, human blood CD34+ cells co-cultured for five days with MSC layers at various O2 concentrations (20%, 12.5% and 3% O2. We demonstrated that IL-17 enhances CD34+ and total CFC production during the five days of MSC/CD34+ co-culture. This effect depends upon the O2 concentration, reaching its maximum at 3% O2, and is more pronounced on erythroid progenitors (BFU-E). In addition, the stimulation of IL-6 production by IL-17 in MSC cultures and co-cultures is enhanced by low O2 concentration. The expression of some differentiation markers (CD34, CD13 and CD41) on haematopoietic cells in co-cultures also depends upon the oxygen concentration. Our results strengthen the concept that physiological levels of O2 (mistakenly called hypoxia), should be considered as an important environmental factor that significantly influences cytokine activity.

  6. Molecular analysis of endothelial progenitor cell (EPC subtypes reveals two distinct cell populations with different identities

    Directory of Open Access Journals (Sweden)

    Simpson David A

    2010-05-01

    Full Text Available Abstract Background The term endothelial progenitor cells (EPCs is currently used to refer to cell populations which are quite dissimilar in terms of biological properties. This study provides a detailed molecular fingerprint for two EPC subtypes: early EPCs (eEPCs and outgrowth endothelial cells (OECs. Methods Human blood-derived eEPCs and OECs were characterised by using genome-wide transcriptional profiling, 2D protein electrophoresis, and electron microscopy. Comparative analysis at the transcript and protein level included monocytes and mature endothelial cells as reference cell types. Results Our data show that eEPCs and OECs have strikingly different gene expression signatures. Many highly expressed transcripts in eEPCs are haematopoietic specific (RUNX1, WAS, LYN with links to immunity and inflammation (TLRs, CD14, HLAs, whereas many transcripts involved in vascular development and angiogenesis-related signalling pathways (Tie2, eNOS, Ephrins are highly expressed in OECs. Comparative analysis with monocytes and mature endothelial cells clusters eEPCs with monocytes, while OECs segment with endothelial cells. Similarly, proteomic analysis revealed that 90% of spots identified by 2-D gel analysis are common between OECs and endothelial cells while eEPCs share 77% with monocytes. In line with the expression pattern of caveolins and cadherins identified by microarray analysis, ultrastructural evaluation highlighted the presence of caveolae and adherens junctions only in OECs. Conclusions This study provides evidence that eEPCs are haematopoietic cells with a molecular phenotype linked to monocytes; whereas OECs exhibit commitment to the endothelial lineage. These findings indicate that OECs might be an attractive cell candidate for inducing therapeutic angiogenesis, while eEPC should be used with caution because of their monocytic nature.

  7. IN UTERO HAEMATOPOIETIC STEM CELL TRANSPLANTATION (IUHSCT

    Directory of Open Access Journals (Sweden)

    Maria Concetta Renda

    2009-12-01

    Among 46 cases of  IUHSCT reported in humans, successful engraftment  was obtained only in cases of  X-SCID. Useful levels of chimerism has not been achieved in non-immunodeficiency diseases, and  a detectable engrafment , was  reported only in one case  of  ß-thalassemia transplanted at 12 weeks of gestation  by fetal liver cells  In one a-thalassemia case, where a-globin-dependent hemoglobin production and anemia are present during fetal period, microchimerism  and tolerance were suggested . To overcome the IUHSCT engraftment barriers , it is necessary to develop strategies to improve the competitive capacity of donor cells and  to define the gestational age of the possible immunological “window of opportunity” in the human fetus. In utero haematopoietic stem cell transplantation (IUHSCT is a non-myeloablative promising approach for the prenatal treatment of a variety of genetic disorders and  could be an alternative  option to therapeutical abortion in some congenital diseases like haematological hereditary  syndromes.

  8. Human placenta-derived mesenchymal progenitor cells support culture expansion of long-term culture-initiating cells from cord blood CD34+ cells

    Institute of Scientific and Technical Information of China (English)

    YiZhanga; ChangdongLi; XiaoxiaJiang; ShuangxiZhang; YingWu; BingLiu; PeihsienTang; NingMao

    2005-01-01

    Objective. Allogeneic transplantation with umbilical cord blood (UCB) in adult recipients is limited mainly by a low CD34+ cell dose. To overcome this shortcoming, human placenta as a novel source of human mesenchymal progenitor cell (MPC) was incorporated in an attempt to expand CD34+ ceils from UCB in vitro.Materials and Methods. Human placenta MPC was isolated and characterized by morphologic,immunophenotypical, and functional analysis. UCB CD34+ cells were expanded by coculturewith placeutal MPC. Suitable aliquots of cells were used to monitor cell production, elonogenie activity, and tong-term culture-initiating culture (LTC-IC) output. Finally, the immunoregulatory effect of placental MPC was evaluated by T-cell proliferation assay.Results. In its undifferentiated state, placental MPC displayed fibroblastoid morphology; was CD73, CD105, CD29, CD44, HLA-ABC, and CD166 positive; produced fibronectin, laminin,and vimentin; but was negative for CD14, CD31, CD34, CD45, HLA-DR, and α-smooth muscle actin. Functionally, it could be induced into adipocytes, osteocytes, and chondrocytes.In vitro expansion of UCB hematopoietic cells, when cocultured with placental MPC in the presence of eytokines, was significantly enhanced: CD34+ cells by 14.89±2.32 fold; colonyforming cell (CFC) by 36.73±5.79 told; and LTC-IC by 7.43±2.66 fold. Moreover, placental MPC could suppress T-cell proliferation induced by cellular stimuli.Conclusion. These results strongly suggest that human placental MPC may be a suitable feeder layer for expansion of hematopoietic progenitors from UCB in vitro.

  9. Fetal exposure to a diabetic intrauterine environment resulted in a failure of cord blood endothelial progenitor cell adaptation against chronic hypoxia

    Science.gov (United States)

    Dincer, U Deniz

    2015-01-01

    Gestational diabetes mellitus (GDM) has long-term health consequences, and fetal exposure to a diabetic intrauterine environment increases cardiovascular risk for her adult offspring. Some part of this could be related to their endothelial progenitor cells (EPCs). Understanding the vessel-forming ability of human umbilical cord blood (HUCB)-derived endothelial colony-forming cells (ECFCs) against pathological stress such as GDM response to hypoxia could generate new therapeutic strategies. This study aims to investigate the role of chronic hypoxia in EPCs functional and vessel-forming ability in GDM subjects. Each ECFC was expressed in endothelial and pro-angiogenic specific markers, namely endothelial nitric oxide synthase (eNOS), platelet (PECAM-1) endothelial cell adhesion molecule 1, vascular endothelial-cadherin CdH5 (Ca-dependent cell adhesion molecule), vascular endothelial growth factor A, (VEGFA) and insulin-like growth factor 1 (IGF1). Chronic hypoxia did not affect CdH5, but PECAM1 MRNA expressions were increased in control and GDM subjects. Control hypoxic and GDM normoxic VEGFA MRNA expressions and hypoxia-inducible factor 1-alpha (HIF1α) protein expressions were significantly increased in HUCB ECFCs. GDM resulted in most failure of HUCB ECFC adaptation and eNOS protein expressions against chronic hypoxia. Chronic hypoxia resulted in an overall decline in HUCB ECFCs’ proliferative ability due to reduction of clonogenic capacity and diminished vessel formation. Furthermore, GDM also resulted in most failure of cord blood ECFC adaptation against chronic hypoxic environment. PMID:25565870

  10. Stochastic dynamics of interacting haematopoietic stem cell niche lineages.

    Directory of Open Access Journals (Sweden)

    Tamás Székely

    2014-09-01

    Full Text Available Since we still know very little about stem cells in their natural environment, it is useful to explore their dynamics through modelling and simulation, as well as experimentally. Most models of stem cell systems are based on deterministic differential equations that ignore the natural heterogeneity of stem cell populations. This is not appropriate at the level of individual cells and niches, when randomness is more likely to affect dynamics. In this paper, we introduce a fast stochastic method for simulating a metapopulation of stem cell niche lineages, that is, many sub-populations that together form a heterogeneous metapopulation, over time. By selecting the common limiting timestep, our method ensures that the entire metapopulation is simulated synchronously. This is important, as it allows us to introduce interactions between separate niche lineages, which would otherwise be impossible. We expand our method to enable the coupling of many lineages into niche groups, where differentiated cells are pooled within each niche group. Using this method, we explore the dynamics of the haematopoietic system from a demand control system perspective. We find that coupling together niche lineages allows the organism to regulate blood cell numbers as closely as possible to the homeostatic optimum. Furthermore, coupled lineages respond better than uncoupled ones to random perturbations, here the loss of some myeloid cells. This could imply that it is advantageous for an organism to connect together its niche lineages into groups. Our results suggest that a potential fruitful empirical direction will be to understand how stem cell descendants communicate with the niche and how cancer may arise as a result of a failure of such communication.

  11. Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Gang G.; Song, Jikui; Wang, Zhanxin; Dormann, Holger L.; Casadio, Fabio; Li, Haitao; Luo, Jun-Li; Patel, Dinshaw J.; Allis, C. David; (MSKCC); (Scripps); (Rockefeller)

    2009-07-21

    Histone H3 lysine4 methylation (H3K4me) has been proposed as a critical component in regulating gene expression, epigenetic states, and cellular identities. The biological meaning of H3K4me is interpreted by conserved modules including plant homeodomain (PHD) fingers that recognize varied H3K4me states. The dysregulation of PHD fingers has been implicated in several human diseases, including cancers and immune or neurological disorders. Here we report that fusing an H3K4-trimethylation (H3K4me3)-binding PHD finger, such as the carboxy-terminal PHD finger of PHF23 or JARID1A (also known as KDM5A or RBBP2), to a common fusion partner nucleoporin-98 (NUP98) as identified in human leukaemias, generated potent oncoproteins that arrested haematopoietic differentiation and induced acute myeloid leukaemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukaemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukaemic transformation. NUP98-PHD fusion prevented the differentiation-associated removal of H3K4me3 at many loci encoding lineage-specific transcription factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene transcription in murine haematopoietic stem/progenitor cells. Mechanistically, NUP98-PHD fusions act as 'chromatin boundary factors', dominating over polycomb-mediated gene silencing to 'lock' developmentally critical loci into an active chromatin state (H3K4me3 with induced histone acetylation), a state that defined leukaemia stem cells. Collectively, our studies represent, to our knowledge, the first report that deregulation of the PHD finger, an 'effector' of specific histone modification, perturbs the epigenetic dynamics on developmentally critical loci, catastrophizes cellular fate decision-making, and even causes oncogenesis during mammalian development.

  12. Increased Proportion of Hematopoietic Stem and Progenitor Cell Population in Cord Blood of Neonates Born to Mothers with Gestational Diabetes Mellitus.

    Science.gov (United States)

    Hadarits, Orsolya; Zóka, András; Barna, Gábor; Al-Aissa, Zahra; Rosta, Klára; Rigó, János; Kautzky-Willer, Alexandra; Somogyi, Anikó; Firneisz, Gábor

    2016-01-01

    We assessed the hematopoietic stem and progenitor cell (HSPC) population in the cord blood of neonates born to mothers with gestational diabetes mellitus (GDM) in a hypothesis generating pilot study, due to that, neonatal polycythemia may be the consequence of GDM pregnancy. Forty-five pregnant women with GDM (last trimester mean HbA1C = 33.9 mmol/mol) and 42 (nondiabetic) control pregnant women were enrolled after their routine 75 g oral glucose tolerance test (OGTT) between the 24th and 28th gestational week (with expected differences in their mean routine clinical characteristics: plasma glucose at OGTT: 0' = 5.07 vs. 4.62 mM, 120' = 8.9 vs. 5.76 mM, age = 35.07 vs. 31.66 years, prepregnancy body mass index = 27.9 vs. 23.9 kg/m(2), GDM vs. control, respectively) on a voluntary basis after signing the informed consent. EDTA-treated cord blood samples were analyzed by flow cytometry and the software Kaluza1.2 using CD45 and CD34-specific fluorescent antibodies to identify the HSPC population (CD34(+) cells within the CD45(dim) blast gate). The proportion of CD34(+)CD45(dim) HSPCs among the nucleated cells was significantly (P treatment types (P cells in the cord blood may possibly be related to altered fetal stem cell mobilization in GDM pregnancy, yet these results should be interpreted only as preliminary due to the small sample sizes.

  13. The Possible Protective Effect of Bone Marrow Transplantation on the Haematopoietic and Lymphoid Tissues in Gamma-Irradiated Rats

    International Nuclear Information System (INIS)

    The current work was done on male albino rats (Rattus norvegicus) - of about 110 to 150 g body weight - to investigate whether bone marrow (BM) transplantation has a role in reducing the dangerous effect of γ-irradiation on the haematopoietic and lymphoid tissues. Control group, BM-injected group, irradiated group and irradiated BM-injected group were used. All the treated animal groups were sacrificed after 5 weeks of the treatments. The haematological analyses included the blood components (WBCs, RBCs, HGB, HCT, PLT). The biochemical analyses included lactate dehydrogenase, malondialdehyde (MDA) and glutathione (GSH). The histopathological study included the bone marrow, spleen and intestinal lymph nodes. Exposure to γ-radiation induced a significant decrease in certain blood components (white blood cells, red blood cells, haemoglobin content, haematocrit value, blood platelets count) and GSH level, and a significant increase in lactate dehydrogenase and MDA levels. Reduction in bone marrow components, decrease in cell populations of the spleen tissue and atrophy of lymph nodes tissue were recorded. BM transplantation after 3 hours to whole body gamma-radiation restored the value of the haematocrit, partially ameliorated the other blood component (WBCs, RBCs, HGB, HCT, PLT) and demonstrated a significant preservation of the bone marrow components and scanty adipose cells’ replacement. An increase in cellularity of the periarteriolar lymphocyte sheath of the white pulps in the spleen tissue and the presence of follicular hyperplasia in the lymph nodes tissue were detected. In Conclusion, BM transplantation exerts a protective against radiation exposure on the haematopoietic and lymphoid tissues of the irradiatedon the haematopoietic and lymphoid tissues of the irradiated animals

  14. Further phenotypic characterization of the primitive lineage− CD34+CD38−CD90+CD45RA− hematopoietic stem cell/progenitor cell sub-population isolated from cord blood, mobilized peripheral blood and patients with chronic myelogenous leukemia

    International Nuclear Information System (INIS)

    The most primitive hematopoietic stem cell (HSC)/progenitor cell (PC) population reported to date is characterized as being Lin−CD34+CD38−CD90+CD45R. We have a long-standing interest in comparing the characteristics of hematopoietic progenitor cell populations enriched from normal subjects and patients with chronic myelogenous leukemia (CML). In order to investigate further purification of HSCs and for potential targetable differences between the very primitive normal and CML stem/PCs, we have phenotypically compared the normal and CML Lin−CD34+CD38−CD90+CD45RA− HSC/PC populations. The additional antigens analyzed were HLA-DR, the receptor tyrosine kinases c-kit and Tie2, the interleukin-3 cytokine receptor, CD33 and the activation antigen CD69, the latter of which was recently reported to be selectively elevated in cell lines expressing the Bcr-Abl tyrosine kinase. Notably, we found a strikingly low percentage of cells from the HSC/PC sub-population isolated from CML patients that were found to express the c-kit receptor (<1%) compared with the percentages of HSC/PCs expressing the c-kitR isolated from umbilical cord blood (50%) and mobilized peripheral blood (10%). Surprisingly, Tie2 receptor expression within the HSC/PC subset was extremely low from both normal and CML samples. Using in vivo transplantation studies, we provide evidence that HLA-DR, c-kitR, Tie2 and IL-3R may not be suitable markers for further partitioning of HSCs from the Lin−CD34+CD38−CD90+CD45RA− sub-population

  15. A comparison of umbilical cord blood-derived endothelial progenitor and mononuclear cell transplantation for the treatment of acute hindlimb ischemia

    Directory of Open Access Journals (Sweden)

    Phuc Van Pham

    2014-01-01

    Full Text Available Acute lower limb ischemia is a common peripheral artery disease whose treatment presents many difficulties. Stem cell transplantation is considered a novel and promising method of treating this disease. Umbilical cord blood (UCB is rich in stem cells, including hematopoietic stem cells (HSCs, mesenchymal stem cells (MSCs and endothelial progenitor cells (EPCs. However, historically, banked umbilical cord blood has been used mainly to treat blood-related diseases. Therefore, this study compared the efficacy of umbilical cord bloodderived mononuclear cells (UCB-MNCs with EPC transplantation for the treatment of acute hindlimb ischemia (ALI in mouse models. MNCs were isolated from UCB by Ficoll gradient centrifugation, after which the EPCs were sorted based on CD34+ and CD133+ markers and cultured according to a previously published protocol. To induce ALI, mice were immuno-suppressed using busulfan (BU and cyclophosphamide (CY, after which the femoral arteries were burned. Induction of ALI in the immune suppressed mice was confirmed by the grade of tissue damage, pedal frequency in water, tissue edema, changes in histology, total white blood cell count, and white blood cell composition. Model mice were injected with a dose of MNCs or EPCs and un-treated control mice were injected with phosphate buffered saline. The efficiency of treatment was evaluated by comparing the grade of tissue damage between the three groups of mice. Mice aged 6 and ndash;12 months were suitable for ALI, with 100% of mice exhibiting ischemia from grade I 10%, grade III 50%, grade IV 40%. For all ALI mice, a gradual increase in pedal frequency in water, increased tissue edema, necrosis of muscle tissue, and loss of hindlimb function were observed after 20 days. Transplanted MNCs and EPCs significantly improved hindlimb ischemia compared with control treatment. Moreover, EPC transplantation significantly improved hindlimb ischemia compared with MNC transplantation. Following

  16. Preclinical Evaluation of the Immunomodulatory Properties of Cardiac Adipose Tissue Progenitor Cells Using Umbilical Cord Blood Mesenchymal Stem Cells: A Direct Comparative Study

    Directory of Open Access Journals (Sweden)

    Isaac Perea-Gil

    2015-01-01

    Full Text Available Cell-based strategies to regenerate injured myocardial tissue have emerged over the past decade, but the optimum cell type is still under scrutiny. In this context, human adult epicardial fat surrounding the heart has been characterized as a reservoir of mesenchymal-like progenitor cells (cardiac ATDPCs with potential clinical benefits. However, additional data on the possibility that these cells could trigger a deleterious immune response following implantation are needed. Thus, in the presented study, we took advantage of the well-established low immunogenicity of umbilical cord blood-derived mesenchymal stem cells (UCBMSCs to comparatively assess the immunomodulatory properties of cardiac ATDPCs in an in vitro allostimulatory assay using allogeneic mature monocyte-derived dendritic cells (MDDCs. Similar to UCBMSCs, increasing amounts of seeded cardiac ATDPCs suppressed the alloproliferation of T cells in a dose-dependent manner. Secretion of proinflammatory cytokines (IL6, TNFα, and IFNγ was also specifically modulated by the different numbers of cardiac ATDPCs cocultured. In summary, we show that cardiac ATDPCs abrogate T cell alloproliferation upon stimulation with allogeneic mature MDDCs, suggesting that they could further regulate a possible harmful immune response in vivo. Additionally, UCBMSCs can be considered as valuable tools to preclinically predict the immunogenicity of prospective regenerative cells.

  17. Stable Delivery of CCR5-Directed shRNA into Human Primary Peripheral Blood Mononuclear Cells and Hematopoietic Stem/Progenitor Cells via a Lentiviral Vector

    Science.gov (United States)

    Shimizu, Saki; Yadav, Swati Seth; An, Dong Sung

    2016-01-01

    RNAi is a powerful tool to achieve suppression of a specific gene expression and therefore it has tremendous potential for gene therapy applications. A number of vector systems have been developed to express short-hairpin RNAs (shRNAs) to produce siRNAs within mammalian T-cells, primary hematopoietic stem/progenitor cells (HSPC), human peripheral blood mononuclear cells, and in animal model systems. Among these, vectors based on lentivirus backbones have significantly transformed our ability to transfer shRNAs into nondividing cells, such as HSPC, resulting in high transduction efficiencies. However, delivery and long-term expression of shRNAs should be carefully optimized for efficient knock down of target gene without causing cytotoxicity in mammalian cells. Here, we describe our protocols for the development of shRNA against a major HIV co-receptor/chemokine receptor CCR5 and the use of lentiviral vectors for stable shRNA delivery and expression in primary human PBMC and HSPC. PMID:26472455

  18. Involvement of placental/umbilical cord blood acid-base status and gas values on the radiosensitivity of human fetal/neonatal hematopoietic stem/progenitor cells

    International Nuclear Information System (INIS)

    Arterial cord blood (CB) acid-base status and gas values, such as pH, PCO2, PO2, HCO3- and base excess, provide useful information on the fetal and neonatal condition. However, it remains unknown whether these values affect the radiosensitivity of fetal/neonatal hematopoiesis. The present study evaluated the relationship between arterial CB acid-base status, gas values, and the radiosensitivity of CB hematopoietic stem/progenitor cells (HSPCs). A total of 25 CB units were collected. The arterial CB acid-base status and gas values were measured within 30 min of delivery. The CD34+ HSPCs obtained from CB were exposed to 2 Gy X-irradiation, and then assayed for colony-forming unit-granulocyte-macrophage, burst-forming unit-erythroid (BFU-E), and colony-forming unit-granulocyte erythroid, macrophage and megakaryocyte cells. Acid-base status and gas values for PCO2 and HCO3- showed a statistically significant negative correlation with the surviving fraction of BFU-E. In addition, a significant positive correlation was observed between gestational age and PCO2. Moreover, the surviving fraction of BFU-E showed a significant negative correlation with gestational age. Thus, HSPCs obtained from CB with high PCO2/HCO3- levels were sensitive to X-irradiation, which suggests that the status of arterial PCO2/HCO3- influences the radiosensitivity of fetal/neonatal hematopoiesis, especially erythropoiesis. (author)

  19. Endometrial aspiration biopsy: a non-invasive method of obtaining functional lymphoid progenitor cells and mature natural killer cells.

    LENUS (Irish Health Repository)

    McMenamin, Moya

    2012-09-01

    The aim of this study was to compare the efficacy of endometrial aspiration biopsy (EAB) with the more traditional dilatation and curettage (D&C) for the procurement of lymphoid progenitor cells and uterine natural killer (NK) populations in endometrial tissue. This prospective observational study conducted in a tertiary referral university hospital examined endometrium obtained from 32 women admitted for laparoscopic gynaecological procedures. Each participant had endometrium sampled using both EAB and D&C. Both methods were assessed as a source of uterine NK and lymphoid progenitor cells. Similar proportions of mature CD45+CD56+ NK cells (range 25.4-36.2%) and CD45+CD34+ lymphoid progenitors (range 1.2-2.0%) were found in tissue obtained using both EAB and D&C. These cells were adequate for flow cytometric analysis, magnetic bead separation and culture. Colony formation by the CD34+ population demonstrated maturational potential. Tissues obtained via endometrial biopsy and D&C are equivalent, by analysis of uterine NK and lymphoid progenitor cells. The aim of this study was to compare two methods of endometrial sampling - endometrial aspiration biopsy and traditional dilatation and curettage - for the procurement of haematopoietic stem cells and uterine natural killer (NK) populations in endometrial tissue. Thirty-two women who had gynaecological procedures in a tertiary referral hospital participated in this study and had endometrial tissue collected via both methods. Similar populations of mature NK cells and haematopoietic stem cells were found in tissue obtained using both endometrial aspiration biopsy and dilatation and curettage. Tissue obtained via endometrial aspiration biopsy was adequate for the culture and growth of haematopoietic stem cells. We conclude that tissue obtained via endometrial biopsy and dilatation and curettage is equivalent, by analysis of uterine NK and haematopoietic stem cells using flow cytometry. This has implications for further

  20. A gene trap transposon eliminates haematopoietic expression of zebrafish Gfi1aa, but does not interfere with haematopoiesis.

    Science.gov (United States)

    Thambyrajah, Roshana; Ucanok, Deniz; Jalali, Maryam; Hough, Yasmin; Wilkinson, Robert Neil; McMahon, Kathryn; Moore, Chris; Gering, Martin

    2016-09-01

    A transposon-mediated gene trap screen identified the zebrafish line qmc551 that expresses a GFP reporter in primitive erythrocytes and also in haemogenic endothelial cells, which give rise to haematopoietic stem and progenitor cells (HSPCs) that seed sites of larval and adult haematopoiesis. The transposon that mediates this GFP expression is located in intron 1 of the gfi1aa gene, one of three zebrafish paralogs that encode transcriptional repressors homologous to mammalian Gfi1 and Gfi1b proteins. In qmc551 transgenics, GFP expression is under the control of the endogenous gfi1aa promoter, recapitulates early gfi1aa expression and allows live observation of gfi1aa promoter activity. While the transposon integration interferes with the expression of gfi1aa mRNA in haematopoietic cells, homozygous qmc551 fish are viable and fertile, and display normal primitive and definitive haematopoiesis. Retained expression of Gfi1b in primitive erythrocytes and up-regulation of Gfi1ab at the onset of definitive haematopoiesis in homozygous qmc551 carriers, are sufficient to allow normal haematopoiesis. This finding contradicts previously published morpholino data that suggested an essential role for zebrafish Gfi1aa in primitive erythropoiesis. PMID:27432513

  1. Combined intermittent hypoxia and surface muscle electrostimulation as a method to increase peripheral blood progenitor cell concentration

    Directory of Open Access Journals (Sweden)

    Azqueta Carmen

    2009-10-01

    Full Text Available Abstract Background Our goal was to determine whether short-term intermittent hypoxia exposure, at a level well tolerated by healthy humans and previously shown by our group to increase EPO and erythropoiesis, could mobilize hematopoietic stem cells (HSC and increase their presence in peripheral circulation. Methods Four healthy male subjects were subjected to three different protocols: one with only a hypoxic stimulus (OH, another with a hypoxic stimulus plus muscle electrostimulation (HME and the third with only muscle electrostimulation (OME. Intermittent hypobaric hypoxia exposure consisted of only three sessions of three hours at barometric pressure 540 hPa (equivalent to an altitude of 5000 m for three consecutive days, whereas muscular electrostimulation was performed in two separate periods of 25 min in each session. Blood samples were obtained from an antecubital vein on three consecutive days immediately before the experiment and 24 h, 48 h, 4 days and 7 days after the last day of hypoxic exposure. Results There was a clear increase in the number of circulating CD34+ cells after combined hypobaric hypoxia and muscular electrostimulation. This response was not observed after the isolated application of the same stimuli. Conclusion Our results open a new application field for hypobaric systems as a way to increase efficiency in peripheral HSC collection.

  2. IN UTERO HAEMATOPOIETIC STEM CELL TRANSPLANTATION (IUHSCT

    Directory of Open Access Journals (Sweden)

    Aurelio Maggio

    2009-06-01

    Full Text Available

    In utero haematopoietic stem cell transplantation (IUHSCT is a non-myeloablative approach for the prenatal treatment of genetic disorders. However, in target disorders, where there is not a selective advantage for donor cells, a useful donor-cell  chimerism  has not been achieved 

    There are three  possible  barriers  to engraftment following IUHSCT :  limited space in the fetus due to host-cell competition; the large number of donor cells needed, and the immunological asset of recipient .

    Animal models have shown different levels of resistance to IUHSCT engraftment.  In primate, goat, rat and mouse  the levels of engraftment that has been achieved were low and not  therapeutic.

  3. High-dose cyclophosphamide followed by autologous peripheral blood progenitor cell transplantation improves the salvage treatment for persistent or sensitive relapsed malignant lymphoma

    Directory of Open Access Journals (Sweden)

    Baldissera R.C.

    2002-01-01

    Full Text Available Trials have demonstrated that high-dose escalation followed by autologous transplantation can promote better long-term survival as salvage treatment in malignant lymphomas. The aim of the present nonrandomized clinical trial was to demonstrate the role of high-dose cyclophosphamide (HDCY in reducing tumor burden and also to determine the effectiveness of HDCY followed by etoposide (VP-16 and methotrexate (MTX in Hodgkin's disease plus high-dose therapy with peripheral blood progenitor cell (PBPC transplantation as salvage treatment. From 1998 to 2000, 33 patients with a median age of 33 years (13-65 affected by aggressive non-Hodgkin's lymphoma (NHL (60.6% or persistent or relapsed Hodgkin's disease (39.4% were enrolled and treated using high dose escalation (HDCY + HDVP-16 plus HDMTX in Hodgkin's disease followed by autologous PBPC transplantation. On an "intention to treat" basis, 33 patients with malignant lymphomas were evaluated. The overall median follow-up was 400 days (40-1233. Thirty-one patients underwent autografting and received a median of 6.19 x 10(6/kg (1.07-29.3 CD34+ cells. Patients who were chemosensitive to HDCY (N = 22 and patients who were chemoresistant (N = 11 presented an overall survival of 96 and 15%, respectively (P<0.0001. Overall survival was 92% for chemosensitive patients and 0% for patients who were still chemoresistant before transplantation (P<0.0001. Toxicity-related mortality was 12% (four patients, related to HDCY in two cases and to transplant in the other two. HDCY + HDVP-16 plus HDMTX in only Hodgkin's disease followed by autologous PBPC proved to be effective and safe as salvage treatment for chemosensitive patients affected by aggressive NHL and Hodgkin's disease, with acceptable mortality rates related to sequential treatment.

  4. Incidence of human herpes virus-6 and human cytomegalovirus infections in donated bone marrow and umbilical cord blood hematopoietic stem cells

    Directory of Open Access Journals (Sweden)

    Behzad-Behbahani A

    2008-01-01

    Full Text Available This study examined the incidence of human herpes virus-6 (HHV-6 and human cytomegalovirus (HCMV infections that are potentially transmitted to haematopoietic stem cells (HSC transplant recipients via bone marrow (BM or umbilical cord blood (UCB. Bone marrow progenitor cells were collected from 30 allogenic BM donors. UCB HSC were collected from 34 subjects. The extracted DNA was then processed using nested polymerase chain reaction (nPCR technique. HCMV and HHV-6 serological status were determined by enzyme immunoassay (EIA. Nested PCR identified HCMV in 22 (73% of 30 samples of BM progenitor cells but in only eight (23.5% of 34 samples of UBC HSC ( P = 0.001. HHV-6 DNA was detected in 11 (36.6% of 30 BM progenitor cells and in only one (2.9% of 34 UBC cells ( P = 0.002. Both HHV-6 and HCMV infections were determined in nine (26.5% of 34 bone marrow samples. The results indicate that, the risk of HCMV and HHV-6 via BM progenitor cells is higher than transmission by UCB cells ( P= 0.04.

  5. Definition of the variables affecting efficacy of immunodepletion ex vivo of peripheral blood progenitor cell grafts by alemtuzumab (Campath in the bag).

    Science.gov (United States)

    Novitzky, Nicolas; Davison, Glenda; Abdulla, Rygana; Mowla, Shaheen

    2013-12-01

    The immunodepleting effects of alemtuzumab on peripheral blood progenitor cell (PBPC) grafts for stem cell transplantation need to be better defined. The optimal graft cell concentration, antibody dose, need for complement, and whether alemtuzumab is infused with the graft during transplantation remain unclear. PBPC from 6 normal allogeneic stem cell donors harvested by apheresis were first quantitated and the cellular content defined by flow cytometry. Mononuclear cells were then incubated with incremental concentrations of alemtuzumab (.00001, .0001, .001, and .01 mg/mL) for 30 minutes at 20°C or in cell dose responses with 1, 5, and 10 × 10(6) mononuclear cells/mL added to a fixed dose of .001 mg/mL of alemtuzumab with or without a source of complement. Cells were enumerated and analyzed by flow cytometry before and after exposure to alemtuzumab. To determine the presence of unbound anti-CD52, the supernatant of the cell dose responses were tested using the ELISA assay. Selected CD34+ lineage-negative cells were incubated with antibody at the same working concentrations and conditions and cultured in granulocyte-macrophage colony-forming unit assay. The colony numbers were compared with control cultures devoid of the antibody. Incremental concentrations of alemtuzumab led to a significant (2 log) reduction in CD3, CD4, and CD8 populations, which plateaued at .001 mg/mL. Addition of complement led to a further significant reduction in the CD4 and CD8 cells. The maximum CD4 (3 log) and CD8 (2 log) cell death was obtained at 10 × 10(6) cells/mL. Analysis of supernatants for soluble alemtuzumab by ELISA showed a significant reduction in the free antibody concentration when the cell number was increased from 1 to 10 × 10(6) cells/mL implying utilization/binding of the antibody by target cells. Incremental concentrations of alemtuzumab did not affect the number of granulocyte-macrophage colony-forming units. Alemtuzumab depletes all cells expressing the CD52

  6. The small GTPase RhoH is an atypical regulator of haematopoietic cells

    Directory of Open Access Journals (Sweden)

    Kubatzky Katharina F

    2008-09-01

    Full Text Available Abstract Rho GTPases are a distinct subfamily of the superfamily of Ras GTPases. The best-characterised members are RhoA, Rac and Cdc42 that regulate many diverse actions such as actin cytoskeleton reorganisation, adhesion, motility as well as cell proliferation, differentiation and gene transcription. Among the 20 members of that family, only Rac2 and RhoH show an expression restricted to the haematopoietic lineage. RhoH was first discovered in 1995 as a fusion transcript with the transcriptional repressor LAZ3/BCL6. It was therefore initially named translation three four (TTF but later on renamed RhoH due to its close relationship to the Ras/Rho family of GTPases. Since then, RhoH has been implicated in human cancer as the gene is subject to somatic hypermutation and by the detection of RHOH as a translocation partner for LAZ3/BCL6 or other genes in human lymphomas. Underexpression of RhoH is found in hairy cell leukaemia and acute myeloid leukaemia. Some of the amino acids that are crucial for GTPase activity are mutated in RhoH so that the protein is a GTPase-deficient, so-called atypical Rho GTPase. Therefore other mechanisms of regulating RhoH activity have been described. These include regulation at the mRNA level and tyrosine phosphorylation of the protein's unique ITAM-like motif. The C-terminal CaaX box of RhoH is mainly a target for farnesyl-transferase but can also be modified by geranylgeranyl-transferase. Isoprenylation of RhoH and changes in subcellular localisation may be an additional factor to fine-tune signalling. Little is currently known about its signalling, regulation or interaction partners. Recent studies have shown that RhoH negatively influences the proliferation and homing of murine haematopoietic progenitor cells, presumably by acting as an antagonist for Rac1. In leukocytes, RhoH is needed to keep the cells in a resting, non-adhesive state, but the exact mechanism has yet to be elucidated. RhoH has also been

  7. Polycomb Cbx family members mediate the balance between haematopoietic stem cell self-renewal and differentiation

    DEFF Research Database (Denmark)

    Klauke, Karin; Radulović, Višnja; Broekhuis, Mathilde;

    2013-01-01

    The balance between self-renewal and differentiation of adult stem cells is essential for tissue homeostasis. Here we show that in the haematopoietic system this process is governed by polycomb chromobox (Cbx) proteins. Cbx7 is specifically expressed in haematopoietic stem cells (HSCs), and its...

  8. Polycomb Cbx family members mediate the balance between haematopoietic stem cell self-renewal and differentiation

    NARCIS (Netherlands)

    Klauke, Karin; Radulovic, Visnja; Broekhuis, Mathilde; Weersing, Ellen; Zwart, Erik; Olthof, Sandra; Ritsema, Martha; Bruggeman, Sophia; Wu, Xudong; Helin, Kristian; Bystrykh, Leonid; de Haan, Gerald

    2013-01-01

    The balance between self-renewal and differentiation of adult stem cells is essential for tissue homeostasis. Here we show that in the haematopoietic system this process is governed by polycomb chromobox (Cbx) proteins. Cbx7 is specifically expressed in haematopoietic stem cells (HSCs), and its over

  9. Reproduction of bovine neonatal pancytopenia (BNP) by feeding pooled colostrum reveals variable alloantibody damage to different haematopoietic lineages.

    Science.gov (United States)

    Bell, Charlotte R; Rocchi, Mara S; Dagleish, Mark P; Melzi, Eleonora; Ballingall, Keith T; Connelly, Maira; Kerr, Morag G; Scholes, Sandra F E; Willoughby, Kim

    2013-02-15

    Bovine neonatal pancytopenia (BNP) is a recently described haemorrhagic disease of calves characterised by thrombocytopenia, leucopenia and bone marrow depletion. Feeding colostrum from cows that have previously produced a BNP affected calf has been shown to induce the disease in some calves, leading to the hypothesis that alloantibodies in colostrum from dams of affected calves mediate destruction of blood and bone marrow cells in the recipient calves. The aims of the current experimental study were first to confirm the role of colostrum-derived antibody in mediating the disease and second to investigate the haematopoietic cell lineages and maturation stages depleted by the causative antibodies. Clinical, haematological and pathological changes were examined in 5 calves given a standardised pool of colostrum from known BNP dams, and 5 control calves given an equivalent pool of colostrum from non-BNP dams. All calves fed challenge colostrum showed progressive depletion of bone marrow haematopoietic cells and haematological changes consistent with the development of BNP. Administration of a standardised dose of the same colostrum pool to each calf resulted in a consistent response within the groups, allowing detailed interpretation of the cellular changes not previously described. Analyses of blood and serial bone marrow changes revealed evidence of differential effects on different blood cell lineages. Peripheral blood cell depletion was confined to leucocytes and platelets, while bone marrow damage occurred to the primitive precursors and lineage committed cells of the thrombocyte, lymphocyte and monocyte lineages, but only to the more primitive precursors in the neutrophil, erythrocyte and eosinophil lineages. Such differences between lineages may reflect cell type-dependent differences in levels of expression or conformational nature of the target antigens. PMID:23273932

  10. Ex vivo expansion of hematopoietic stem- and progenitor cells from cord blood in coculture with mesenchymal stroma cells from amnion, chorion, Wharton's jelly, amniotic fluid, cord blood, and bone marrow.

    Science.gov (United States)

    Klein, Caroline; Strobel, Julian; Zingsem, Jürgen; Richter, Richard H; Goecke, Tamme W; Beckmann, Matthias W; Eckstein, Reinhold; Weisbach, Volker

    2013-12-01

    In most cases, the amount of hematopoietic stem and progenitor cells (HSPCs) in a single cord blood (CB) unit is not sufficient for allogenic transplantation of adults. Therefore, two CB units are usually required. The ex vivo expansion of HSPCs from CB in coculture with mesenchymal stroma cells (MSCs) might be an alternative. It was investigated, whether bone marrow-derived MSCs, which have to be obtained in an invasive procedure, introduce a further donor and increases the risk of transmissible infectious diseases for the patient can be replaced by MSCs from amnion, chorion, Wharton's jelly, amniotic fluid, and CB, which can be isolated from placental tissue which is readily available when CB is sampled. In a two-step ex vivo coculture mononuclear cells from cryopreserved CB were cultured with different MSC-feederlayers in a medium supplemented with cytokines (stem cell factor, thrombopoietin [TPO], and granulocyte colony-stimulating factor). Expansion rates were analyzed as well, by long-term culture-initiating cell (LTC-IC) and colony-forming unit (CFU) assays, as by measuring CD34(+)- and CD45(+)-cells. Due to the comparably low number of 5×10(2) to 1×10(4) CD34(+)-cells per cm(2) MSC-monolayer, we observed comparably high expansion rates from 80 to 391,000 for CFU, 70 to 313,000 for CD34(+)-, and 200 to 352,000 for CD45(+)-cells. Expansion of LTC-IC was partly observed. Compared to the literature, we found a better expansion rate of CD34(+)-cells with MSCs from all different sources. This is probably due to the comparably low number of 5×10(2) to 1×10 CD34(+)-cells per cm(2) MSC-monolayer we used. Comparably, high expansion rates were observed from 80 to 391,000 for CFUs, 70 to 313,000 for CD34(+)-, and 200 to 352,000 for CD45(+)-cells. However, the expansion of CD34(+)-cells was significantly more effective with MSCs from bone marrow compared to MSCs from amnion, chorion, and Wharton's jelly. The comparison of MSCs from bone marrow with MSCs from CB and

  11. 循环血液中内皮祖细胞在充血性心力衰竭患者中的表达%Expression of endothelial progenitor cells with the blood circulation in congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    余东彪; 吴继雄

    2012-01-01

    目的 研究内皮祖细胞在充血性心力衰竭患者中的表达情况,并进一步研究其与心衰严重程度的相关性.方法 选择心衰患者96例(纽约心功能分级:Ⅰ级22例,Ⅱ级25例,Ⅲ级26例,Ⅳ级23例)及健康正常人25例(对照组),以CD34、CD45为表面标记,用流式细胞仪测量外周血中的内皮祖细胞数,并同时测量脑钠肽(BNP).结果 心衰患者较对照组BNP水平升高(P<0.01),且心衰的严重程度与BNP呈正相关;在心功能Ⅰ级、Ⅱ级心衰患者中,内皮祖细胞较健康对照组明显升高(P<0.01);心功能Ⅲ级、Ⅳ级患者较健康对照组降低(P<0.05或<0.01).结论 内皮祖细胞在心衰患者中呈现一个双向性改变,即在心衰晚期阶段外周血内皮祖细胞表达较对照组明显下降,而在心衰早期阶段较对照组明显升高,提示受损的内皮祖细胞招募可能参与严重心衰患者的病理生理过程.%Objective To investigate the pattern of endothelial progenitor cells during congestive heart failure and their correlation with the severity. Methods 96 patients with heart failure (NYHA Class Ⅰ: 22 cases, Ⅱ: 25 cases, Ⅲ: 26 cases, Ⅳ: 23 cases) and 25 cases of normal control group were measured CD34, CD45, peripheral blood endothelial progenitor cells number with flow cytometric and simultaneously measured brain natriuretic peptide (BNP) level. Results The heart failure patients increased significantly BNP levels than the control group, and the severity of the heart failure with BNP was positively correlated. Endothelial progenitor cells were increased in NYHA Class I and NYHA Class Ⅱ compared with that in controls ( P < 0. 01 ). Endothelial progenitor cells were significantly decreased in NYHA Class Ⅳ and NYHA Class Ⅲ compared with that in controls (P < 0.05 or P < 0.01). Conclusions Endothelial progenitor cells in the heart failure patients show a biphasic response, with elevation and depression in the early and

  12. Neuroprotective properties of a novel, non-haematopoietic agonist of the erythropoietin receptor

    DEFF Research Database (Denmark)

    Pankratova, Stanislava; Kiryushko, Dar'Ya; Sonn, Katrin;

    2010-01-01

    attenuated seizures, decreased mortality and reduced neurodegeneration in an in vivo model of kainic acid-induced neurotoxicity. In contrast to erythropoietin, Epotris did not stimulate erythropoiesis upon chronic administration. Thus, Epotris is a novel neuroprotective non-haematopoietic erythropoietin...

  13. Controle de esterilidade de produtos de células progenitoras hematopoéticas do sangue periférico Sterility control of hematopoietic progenitor cells from peripheral blood products

    Directory of Open Access Journals (Sweden)

    Igor D. Almeida

    2010-02-01

    Full Text Available A taxa de contaminação microbiana dos produtos de células progenitoras hematopoéticas do sangue periférico é baixa. Neste estudo pesquisou-se a prevalência de hemoculturas positivas em células progenitoras hematopoéticas do sangue periférico (CPHSP no Serviço de Hemoterapia do Hospital de Clínicas de Porto Alegre. Do total de 618 coletas realizadas no período de 2000 a 2007, 26 (4,2% apresentaram contaminação por bactérias. O Staphylococcus coagulase-negativo foi predominantemente isolado nas hemoculturas. A antibioticoterapia pré e pós-infusão foi estabelecida de acordo com o microorganismo e seu antibiograma, sendo que, em cinco das doze infusões contaminadas realizadas, não foram administrados antimicrobianos profilaticamente. Episódios febris foram observados em sete pacientes (58%, enquanto cinco (42% não apresentaram febre. Das doze infusões contaminadas realizadas, seis (50% apresentaram hemocultura pós-descongelamento positivas, enquanto as restantes (50% foram negativas. Isto se deve às propriedades bactericidas do DMSO, de células fagocitose-ativas e de temperaturas muito baixas atingidas na criopreservação. Autores têm relatado sucesso neste procedimento após a infusão desses produtos contaminados com o mínimo de consequências clínicas.The rate of microbial contamination of hematopoietic progenitor cell products from peripheral blood is low. In this study, we investigated the prevalence of positive blood cultures of hematopoietic progenitor cells from peripheral blood in a hemotherapy service. Of a total of 618 samples taken during the period from 2000 to 2007, 26 (4.2% were contaminated by bacteria. Staphylococcus coagulase-negative was the predominant bacterium isolated in blood cultures. Pre- and post-infusion antibiotic therapy was established depending on the microorganism and antibiogram, whereas in five out of twelve contaminated infusions, no antibiotics were administered prophylactically

  14. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Ursula; M; Gehling; Marc; Willems; Kathleen; Schlagner; Ralf; A; Benndorf; Maura; Dandri; Jrg; Petersen; Martina; Sterneck; Joerg-Matthias; Pollok; Dieter; K; Hossfeld; Xavier; Rogiers

    2010-01-01

    AIM:To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS:Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry.Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1(SDF-1) were measured using an enzyme linked immunosorbent assay.RESULTS:Progenitor cells with a CD133 + /CD45 + CD14 + phenotype we...

  15. Clinical outcomes after autologous haematopoietic stem cell transplantation in patients with progressive multiple sclerosis

    Institute of Scientific and Technical Information of China (English)

    XU Juan; JI Bing-xin; SU Li; DONG Hui-qing; SUN Xue-jing; LIU Cong-yan

    2006-01-01

    Background Multiple sclerosis (MS) is a continuously disabling disease and it is unresponsive to high dose steroid and immunomodulation with disease progression. The autologous haematopoietic stem cell transplantation (ASCT) has been introduced in the treatment of refractory forms of multiple sclerosis. In this study, the clinical outcomes followed by ASCT were evaluated for patients with progressive MS.Methods Twenty-two patients with secondary progressive MS were treated with ASCT. Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony stimulating factor. Etoposide,melphalan, carmustin and cytosine arabinoside were administered as conditioning regimen. Outcomes were evaluated by the expanded disability status scale and progression free survival. No maintenance treatment was administered during a median follow-up of 39 months (range, 6 to 59 months).Results No death occurred following the treatment. The overall confirmed progression free survival rate was77% up to 59 months after transplantation which was significantly higher compared with pre-transplantation (P=0.000). Thirteen patients (59%) had remarkable improvement in neurological manifestations, four (18%)stabilized their disability status and five (23%) showed clinical recurrence of active symptoms.Conclusions ASCT as a therapy is safe and available. It can improve or stabilize neurological manifestations in most patients with progressive MS following failure of conventional therapy.

  16. [Effect of metals, benzene, pesticides and ethylene oxide on the haematopoietic system].

    Science.gov (United States)

    Pyszel, Angelika; Wróbel, Tomasz; Szuba, Andrzej; Andrzejak, Ryszard

    2005-01-01

    The hematopoietic system, due to intensive cells proliferation, is very sensitive to toxic substances. Many chemicals, including benzene, pesticides (dithiocarbamines), ethylene oxide and metals (mercury, cadmium, chrome, cobalt, lead, aluminum) exert their toxic effect on the hematopoietic system. Exposure to each of these substances may occur in the work place due to environmental pollution and in municipal or residential areas. Exposure to lead, aluminum, cadmium, and benzene results in the incidence of anemia. In addition, exposure to benzene and its metabolites leads to myelodysplastic syndromes, leukemia, lymphomas and bone marrow aplasia. Ethylene oxide induces neoplasm of the hematopoietic system and lymphomas, especially non-Hodgkin lymphoma. Arsenic compounds act like immunosuppressants. Mercury and chrome affect the immune system by immunosuppression and by evoking autoimmune reactions. Dithiocarbamates are suspected to induce leukemia. An analysis of the pathophysiology of individual substances reveal universal toxic mechanisms. In this paper, the authors discuss the pathomechanism of toxic effects of the aforesaid chemicals on the haematopoietic system and peripheral blood cells from the viewpoint of mutagenesis, apoptosis, myelotoxicity, anemia, immunomodulation, and individual sensitivity.

  17. A novel automated bioreactor for scalable process optimisation of haematopoietic stem cell culture.

    Science.gov (United States)

    Ratcliffe, E; Glen, K E; Workman, V L; Stacey, A J; Thomas, R J

    2012-10-31

    Proliferation and differentiation of haematopoietic stem cells (HSCs) from umbilical cord blood at large scale will potentially underpin production of a number of therapeutic cellular products in development, including erythrocytes and platelets. However, to achieve production processes that are scalable and optimised for cost and quality, scaled down development platforms that can define process parameter tolerances and consequent manufacturing controls are essential. We have demonstrated the potential of a new, automated, 24×15 mL replicate suspension bioreactor system, with online monitoring and control, to develop an HSC proliferation and differentiation process for erythroid committed cells (CD71(+), CD235a(+)). Cell proliferation was relatively robust to cell density and oxygen levels and reached up to 6 population doublings over 10 days. The maximum suspension culture density for a 48 h total media exchange protocol was established to be in the order of 10(7)cells/mL. This system will be valuable for the further HSC suspension culture cost reduction and optimisation necessary before the application of conventional stirred tank technology to scaled manufacture of HSC derived products.

  18. Angiogenesis and vasculogenesis: inducing the growth of new blood vessels and wound healing by stimulation of bone marrow-derived progenitor cell mobilization and homing.

    Science.gov (United States)

    Velazquez, Omaida C

    2007-06-01

    During embryonic development, the vasculature is among the first organs to form and is in charge of maintaining metabolic homeostasis by supplying oxygen and nutrients and removing waste products. As one would expect, blood vessels are critical not only for organ growth in the embryo but also for repair of wounded tissue in the adult. An imbalance in angiogenesis (a time-honored term that globally refers to the growth of new blood vessels) contributes to the pathogenesis of numerous malignant, inflammatory, ischemic, infectious, immune, and wound-healing disorders. This review focuses on the central role of the growth of new blood vessels in ischemic and diabetic wound healing and defines the most current nomenclature that describes the neovascularization process in wounds. There are now two well-defined, distinct, yet interrelated processes for the formation of postnatal new blood vessels, angiogenesis, and vasculogenesis. Reviewed are recent new data on vasculogenesis that promise to advance the field of wound healing.

  19. Effects of Ionizing Radiations on the Haematopoietic Tissue. Proceedings of a Panel on the Effects of Various Types of Ionizing Radiations from Different Sources on Haematopoietic Tissue

    International Nuclear Information System (INIS)

    The atomic energy industry and the medical sciences are making increasing use of gamma and X-irradiation as well as neutron, proton and mixed irradiation of high-energy particles from reactors, both in research work and in the treatment of patients. For this reason the need for a more detailed investigation of the influence of different sources of irradiation on the haematopoietic tissue becomes more urgent from day to day. This task should no longer be considered as a purely scientific one, but rather as a matter of practical application, since an understanding of the radiosensitivity of haematopoietic tissue is essential in treating patients by X-ray or other radioactive therapies, as well as in treating persons involved in radiation accidents, particularly where bone-marrow or organ transplantation is necessary. A panel of experts on ''The Effects of Various Types of Ionizing Radiations from Different Sources on Haematopoietic Tissue'' was convened by the International Atomic Energy Agency at its headquarters in Vienna from 17 to 20 May, 1966. The meeting was attended by 22 experts from 13 countries. The object was to discuss (1) the facts and concepts of normal haematopoiesis and its regulation, (2) the qualitative and quantitative aspects of the effects of conventional radiation sources on haematopoiesis, and (3) the comparative reactions of haematopoietic tissue from different animals after irradiation. The meeting produced a stimulating exchange of ideas, as is witnessed by this publication, which contains all the papers and discussions

  20. T cell reconstitution in allogeneic haematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Kielsen, K; Jordan, K K; Uhlving, H H;

    2015-01-01

    Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although...... it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We...... in patients treated with anti-thymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3(+) : β = -10.6 × 10(6) cells/l, P = 0.0030; CD8(+) : β = -8.4 × 10(6) cells/l, P = 0.061; CD4...

  1. Secondary Malignant Neoplasms Following Haematopoietic Stem Cell Transplantation in Childhood

    Directory of Open Access Journals (Sweden)

    Simon Bomken

    2015-04-01

    Full Text Available Improving survival rates in children with malignancy have been achieved at the cost of a high frequency of late adverse effects of treatment, especially in intensively treated patients such as those undergoing haematopoietic stem cell transplantation (HSCT, many of whom suffer the high burden of chronic toxicity. Secondary malignant neoplasms (SMNs are one of the most devastating late effects, cause much morbidity and are the most frequent cause of late (yet still premature treatment-related mortality. They occur in up to 7% of HSCT recipients by 20 years post-HSCT, and with no evidence yet of a plateau in incidence with longer follow-up. This review describes the epidemiology, pathogenesis, clinical features and risk factors of the three main categories of post-HSCT SMNs. A wide range of solid SMNs has been described, usually occurring 10 years or more post-HSCT, related most often to previous or conditioning radiotherapy. Therapy-related acute myeloid leukaemia/myelodysplasia occurs earlier, typically three to seven years post-HSCT, mainly in recipients of autologous transplant and is related to previous alkylating agent or topoisomerase II inhibitor chemotherapy. Post-transplant lymphoproliferative disorders occur early (usually within two years post-HSCT, usually presenting as Epstein-Barr virus-related B cell non-Hodgkin lymphoma.

  2. File list: His.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 Histone Blood Granulocyte-Macro...edbc.jp/kyushu-u/mm9/assembled/His.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  3. File list: His.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 Histone Blood Granulocyte-Macro...edbc.jp/kyushu-u/mm9/assembled/His.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  4. File list: His.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 Histone Blood Granulocyte-Macro...edbc.jp/kyushu-u/mm9/assembled/His.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  5. File list: His.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 Histone Blood Granulocyte-Macro...edbc.jp/kyushu-u/mm9/assembled/His.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  6. Targeted expansion and regulation of genetically modified cord blood stem/progenitor cells in vitro%靶基因调控的脐血干/祖细胞体外长期扩增与调控

    Institute of Scientific and Technical Information of China (English)

    赵声明; 彭明婷; 顾惜春; 常乃柏

    2008-01-01

    BACKGROUND: Cord blood stem cells are one of ideal target cells for gene therapy, but low gene transferring rate is the main difficulty at recent. Janus kinase tyrosine 2 (JAK2) plays an important role in self-renewing of cord blood stem/progenitor cell12s. Therefore, cord blood CD34+ cell line modified by target-amplified JAK2 genes has been developed yet by using gene regulating expression technique in order to overcome low transferring rate of cord blood genes.OBJECTIVE: To investigate the feasibility and reliability of a long-term amplified regulation for cord blood stem/progenitor cells mediated by transgene JAK2. SETTING: Department of Hematology, Beijing Hospital, Ministry of Health.MATERIALS: The experiment was carried out in the Laboratory of Hematological Department, Beijing Hospital, Ministry of Health from June 2003 to April 2006. Cord blood was derived from umbilical cord which was immediately cut from healthy, full-term and natural-parturition infants and was provided by Department of Obstetrics & Gynecology, Beijing Hospital. The experiment was approved by the local ethical committee, and informed consent was obtained from expectant mothers and their relatives for the use of cord blood cells. MiniMACS magnetic separation apparatus and immunomagnetic beads adsorbing CD34 single antibody were provided by Miltenyi Biotec Company, Germany; flow cytometer by FACScalibur, USA; recombinant human stem cell factor (rhSCF), Flt3 ligand (FL), human interleukin-6 (hIL-6), granulocyte macrophage colony stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and thrombopoeitin (TPO) by PeproTec Company; nude mice of the SPF level by Animal Center of Beijing Medical University.METHODS: Retroviral vector MGI-F2JAK2, which was composed of functional catalytic domain of JAK2 genes and two site proteins (2xF36v, F2) combined with synthetic drug (AP20187) of target gene of small molecules, was constructed. AP20187 might specially combine with F36v to

  7. The haematopoietic response to burning: studies in a splenectomized animal model.

    Science.gov (United States)

    Wallner, S F; Vautrin, R; Katz, J

    1987-02-01

    Several haematopoietic changes occur following burning. These changes are important because they may effect a patient's ability to fight infection and to heal wounds. Studies of haematopoiesis in burned humans are difficult because of the complexity of these patients and because of the difficulty of collecting specimens. We therefore established a mouse model of these haematopoietic events; however, this model differed from the human situation as all three haematopoietic cell lines were being produced by the murine spleen. In this paper, we modified the model by removing the spleen and then repeating our previous studies. After splenectomy, granulocyte production, murine mortality and body weight did not change. Compared with the original model, the modified splenectomy model could not expand erythropoiesis. The result was greater anaemia. This model is, now, a closer simulation of the human situation and will prove useful in studies of haematopoiesis after thermal injury. PMID:3828854

  8. Effect of human cytomegalovirus on proliferation of hematopoietic progenitor cells of cord blood%人类巨细胞病毒感染对脐血造血祖细胞增殖的影响

    Institute of Scientific and Technical Information of China (English)

    刘文君; 金润铭; 付晓冬; 刘斌; 郭渠莲; 邓正华

    2006-01-01

    目的探讨人类巨细胞病毒(HCMV)感染对脐血造血祖细胞(CFU-GM、CFU-E、BFU-E、CFU-Mix及CFU-Mk)体外增殖的抑制作用及其机制.方法20例脐血标本收集于正常足月顺产新生儿.实验共分5组:(1)3个HCMV感染组,每个感染组分别加入0.1 mL的103、104及105空斑形成单位(PFU)HCMV-AD169病毒液于培养体系中;(2)灭活对照组,加入同体积灭活HCMV病毒液;(3)空白对照组,不加HCMV病毒液,代之以同体积的IMDM.采用造血祖细胞体外半固体培养技术,培养、观察、计数HCMV-AD169株对脐血CFU-GM、CFU-E、BFU-E、CFU-Mix及CFU-Mk集落数、抑制率和集落维持时间;并用聚合酶链反应(PCR)技术检测集落细胞内HCMV-DNA.结果(1)在造血祖细胞培养体系中加入不同滴度的HCMV-AD169后,104和105PFU滴度感染对CFU-GM、CFU-E、BFU-E、CFU-Mix及CFU-Mk集落形成均有显著的抑制作用,103PFU滴度感染对CFU-Mix及CFU- Mk集落形成有显著的抑制作用,与空白对照组和灭活对照组比较,差异有显著性(P<0.05).病毒滴度越高,抑制程度越明显(P<0.05).(2)104和105 PFU滴度感染组CFU-GM、CFU-E、BFU-E、CFU-Mix及CFU-Mk集落维持时间较对照组明显缩短(P<0.01),103 PFU滴度感染组CFU-Mix和CFU-Mk集落维持时间较对照组明显缩短(P<0.01).(3)PCR显示3个感染组的CFU-GM、CFU-E、CFU-Mix及CFU-Mk集落细胞内均有HCMV-AD169 DNA存在.结论HCMV-AD169能直接感染CFU-GM、CFU-E、BFU-E、CFU-Mix及CFU-Mk造血祖细胞,并抑制造血祖细胞的增殖,这可能与HCMV感染患儿出现粒细胞减少、血小板减少和贫血等造血功能紊乱有关.%Objective This study was designed to investigate the effect of human cytomegalovirus (HCMV) on the proliferation of colony forming unit granulocyte-macrophage ( CFU-GM ), CFU-erythroid ( CFU-E), burst forming uniterythroid (BFU-E), CFU-multipotential (CFU-Mix) and CFU-megakaryocytic (CFU-Mk) progenitor cells of cord blood in vitro as well as

  9. Genetic and serological typing of European infectious haematopoietic necrosis virus (IHNV) isolates

    DEFF Research Database (Denmark)

    Johansson, Tove; Einer-Jensen, Katja; Batts, William;

    2009-01-01

    Infectious haematopoietic necrosis virus (IHNV) causes the lethal disease infectious haematopoietic necrosis (IHN) in juvenile salmon and trout. The nucleocapsid (N) protein gene and partial glycoprotein (G) gene (nucleotides 457 to 1061) of the European isolates IT-217A, FR-32/87, DE-DF 13....../98 11621, DE-DF 4/99-8/99, AU-9695338 and RU-FR1 were sequenced and compared with IHNV isolates from the North American genogroups U, M and L. In phylogenetic studies the N gene of the Italian, French, German and Austrian isolates clustered in the M genogroup, though in a different subgroup than the...

  10. Endothelial progenitor cells in cardiovascular diseases

    Institute of Scientific and Technical Information of China (English)

    Poay; Sian; Sabrina; Lee; Kian; Keong; Poh

    2014-01-01

    Endothelial dysfunction has been associated with the development of atherosclerosis and cardiovascular diseases. Adult endothelial progenitor cells(EPCs) are derived from hematopoietic stem cells and are capable of forming new blood vessels through a process of vas-culogenesis. There are studies which report correlations between circulating EPCs and cardiovascular risk fac-tors. There are also studies on how pharmacotherapies may influence levels of circulating EPCs. In this review, we discuss the potential role of endothelial progenitor cells as both diagnostic and prognostic biomarkers. In addition, we look at the interaction between cardio-vascular pharmacotherapies and endothelial progenitor cells. We also discuss how EPCs can be used directly and indirectly as a therapeutic agent. Finally, we evalu-ate the challenges facing EPC research and how these may be overcome.

  11. Synergistic Effect of Sodium Butyrate and Thalidomide in the Induction of Fetal Hemoglobin Expression in Erythroid Progenitors Derived from Cord Blood CD133 + Cells

    Directory of Open Access Journals (Sweden)

    Ali Dehghanifard

    2012-07-01

    Full Text Available Background: The use of drugs with the ability to induce production of fetal hemoglobin as a novel therapeutic approach in treating β-Hemoglobinopathies is considered. γ-globin gene expression inducer drugs including sodium butyrate and thalidomide can reduce additional α-globin chains accumulation in erythroid precursors. Materials and Methods: In this experimental study, MACS kit was used to isolate CD133+ cells of umbilical cord blood. Further, the effect of two drugs of thalidomide and sodium butyrate were separately and combined studied on the induction of quantitative expression of β-globin and γ-globin genes in erythroid precursor cells derived from CD133+ stem cells in-vitro. For this purpose, the technique SYBR green Real-time PCR was used.Results: Flow cytometry results showed that approximately 95% of purified cells were CD133+. Real-time PCR results also showed the increased levels of γ-globin mRNA in the cell groups treated with thalidomide, sodium butyrate and combination of drugs as 2.6 and 1.2 and 3.5 times respectively, and for β-globin gene, it is respectively 1.4 and 1.3 and 1.6 times compared with the control group (p<0.05.Conclusion: The study results showed that the mentioned drug combination can act as a pharmaceutical composition affecting the induction of fetal hemoglobin expression in erythroid precursor cells derived from CD133 + cells.

  12. Single-cell analyses of regulatory network perturbations using enhancer-targeting TALEs suggest novel roles for PU.1 during haematopoietic specification.

    Science.gov (United States)

    Wilkinson, Adam C; Kawata, Viviane K S; Schütte, Judith; Gao, Xuefei; Antoniou, Stella; Baumann, Claudia; Woodhouse, Steven; Hannah, Rebecca; Tanaka, Yosuke; Swiers, Gemma; Moignard, Victoria; Fisher, Jasmin; Hidetoshi, Shimauchi; Tijssen, Marloes R; de Bruijn, Marella F T R; Liu, Pentao; Göttgens, Berthold

    2014-10-01

    Transcription factors (TFs) act within wider regulatory networks to control cell identity and fate. Numerous TFs, including Scl (Tal1) and PU.1 (Spi1), are known regulators of developmental and adult haematopoiesis, but how they act within wider TF networks is still poorly understood. Transcription activator-like effectors (TALEs) are a novel class of genetic tool based on the modular DNA-binding domains of Xanthomonas TAL proteins, which enable DNA sequence-specific targeting and the manipulation of endogenous gene expression. Here, we report TALEs engineered to target the PU.1-14kb and Scl+40kb transcriptional enhancers as efficient new tools to perturb the expression of these key haematopoietic TFs. We confirmed the efficiency of these TALEs at the single-cell level using high-throughput RT-qPCR, which also allowed us to assess the consequences of both PU.1 activation and repression on wider TF networks during developmental haematopoiesis. Combined with comprehensive cellular assays, these experiments uncovered novel roles for PU.1 during early haematopoietic specification. Finally, transgenic mouse studies confirmed that the PU.1-14kb element is active at sites of definitive haematopoiesis in vivo and PU.1 is detectable in haemogenic endothelium and early committing blood cells. We therefore establish TALEs as powerful new tools to study the functionality of transcriptional networks that control developmental processes such as early haematopoiesis.

  13. Long-term survival after allogeneic haematopoietic cell transplantation for AML in remission

    DEFF Research Database (Denmark)

    Sengeløv, H; Gerds, T A; Brændstrup, P;

    2013-01-01

    We report the results of non-myeloablative (NM) and myeloablative (MA) conditioning for haematopoietic cell transplantation in 207 consecutive AML patients at a single institution. A total of 122 patients were transplanted in first CR (CR1) and 67 in second CR (CR2). MA conditioning was given to 60...

  14. Growth, endocrine function and quality of life after haematopoietic stem cell transplantation

    NARCIS (Netherlands)

    Bakker, Boudewijn

    2006-01-01

    This thesis contains the results of several studies on the long-term consequences of the myeloablative conditioning for haematopoietic stem cell transplantation (SCT) during infancy and childhood, with the emphasis on late effects on endocrine functions. After a general introduction, effects of tot

  15. Aspergillus galactomannan antigen levels in allogeneic haematopoietic stem cell transplant recipients given total parenteral nutrition.

    NARCIS (Netherlands)

    Blijlevens, N.M.A.; Donnelly, J.P.; Meis, J.F.G.M.; Verweij, P.E.; Pauw, B.E. de

    2002-01-01

    False-positive tests for Aspergillus galactomannan have been reported in neutropenic patients. We failed to detect any circulating antigen during the 2 weeks following allogeneic haematopoietic stem cell transplantation of 12 patients who had severe mucositis but were unable to eat.

  16. The role of gamma delta T cells in haematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Minculescu, L; Sengeløv, H

    2015-01-01

    Although haematopoietic stem cell transplantation (HSCT) is a potential curative treatment for haematological malignancies, it is still a procedure associated with substantial morbidity and mortality due to toxicity, graft-versus-host disease (GVHD) and relapse. Recent attempts of developing safe...

  17. Fibronectin and VLA-4 in haematopoietic stem cell-microenvironment interactions

    Science.gov (United States)

    Williams, David A.; Rios, Maribel; Stephens, Carmella; Patel, Vikram P.

    1991-08-01

    THE self-renewal and differentiation of haematopoietic stem cells occurs in vivo and in vitro in direct contact with cells making up the haematopoietic microenvironment1-4. In this study we used adhesive ligands and blocking antibodies to identify stromal cell-derived extracellular matrix proteins involved in promoting attachment of murine haematopoietic stem cells. Here we report that day-12 colony-forming-unit spleen (CFU-S12)5 cells and reconstituting haematopoietic stem cells attach to the C-terminal, heparin-binding fragment of fibronectin by recognizing the CS-1 peptide of the alternatively spliced non-type III connecting segment (IIICS) of human plasma fibronectin. Furthermore, CFU-S12 stem cells express the α4 subunit of the VLA-4 integrin receptor, which is known to be a receptor for the CS-1 sequence, and monoclonal antibodies against the integrin α4 subunit of VLA-4 block adhesion of CFU-S12 stem cells to plates coated with the C-terminal fibronectin fragment. Finally, polyclonal antibodies against the integrin β1 subunit of VLA-4 inhibit the formation of CFU-S12-derived spleen colonies and medullary haematopoiesis in vivo following intravenous infusion of antibody-treated bone marrow cells.

  18. GFI1 proteins orchestrate the emergence of haematopoietic stem cells through recruitment of LSD1

    NARCIS (Netherlands)

    Thambyrajah, Roshana; Mazan, Milena; Patel, Rahima; Moignard, Victoria; Stefanska, Monika; Marinopoulou, Elli; Li, Yaoyong; Lancrin, Christophe; Clapes, Thomas; Möröy, Tarik; Robin, Catherine; Miller, Crispin; Cowley, Shaun; Göttgens, Berthold; Kouskoff, Valerie; Lacaud, Georges

    2016-01-01

    In vertebrates, the first haematopoietic stem cells (HSCs) with multi-lineage and long-term repopulating potential arise in the AGM (aorta-gonad-mesonephros) region. These HSCs are generated from a rare and transient subset of endothelial cells, called haemogenic endothelium (HE), through an endothe

  19. An economic model to assess the savings from a clinical application of haematopoietic growth factors

    NARCIS (Netherlands)

    deGroot, CAU; Vellenga, E; Rutten, FFH

    1996-01-01

    Patients receiving chemotherapy frequently develop fever and neutropenia. Haematopoietic growth factors (HGFs) may decrease the duration of such episodes or may prevent a febrile neutropenic episode. In this study we introduce a Markov type economic model for the hospital which calculates all releva

  20. Imatinib and nilotinib inhibit hematopoietic progenitor cell growth, but do not prevent adhesion, migration and engraftment of human cord blood CD34+ cells.

    Directory of Open Access Journals (Sweden)

    Ludovic Belle

    Full Text Available BACKGROUND: The availability of tyrosine kinase inhibitors (TKIs has considerably changed the management of Philadelphia chromosome positive leukemia. The BCR-ABL inhibitor imatinib is also known to inhibit the tyrosine kinase of the stem cell factor receptor, c-Kit. Nilotinib is 30 times more potent than imatinib towards BCR-ABL in vitro. Studies in healthy volunteers and patients with chronic myelogenous leukemia or gastrointestinal stromal tumors have shown that therapeutic doses of nilotinib deliver drug levels similar to those of imatinib. The aim of this study was to compare the inhibitory effects of imatinib and nilotinib on proliferation, differentiation, adhesion, migration and engraftment capacities of human cord blood CD34(+ cells. DESIGN AND METHODS: After a 48-hour cell culture with or without TKIs, CFC, LTC-IC, migration, adhesion and cell cycle analysis were performed. In a second time, the impact of these TKIs on engraftment was assessed in a xenotransplantation model using NOD/SCID/IL-2Rγ (null mice. RESULTS: TKIs did not affect LTC-IC frequencies despite in vitro inhibition of CFC formation due to inhibition of CD34(+ cell cycle entry. Adhesion of CD34(+ cells to retronectin was reduced in the presence of either imatinib or nilotinib but only at high concentrations. Migration through a SDF-1α gradient was not changed by cell culture in the presence of TKIs. Finally, bone marrow cellularity and human chimerism were not affected by daily doses of imatinib and nilotinib in a xenogenic transplantation model. No significant difference was seen between TKIs given the equivalent affinity of imatinib and nilotinib for KIT. CONCLUSIONS: These data suggest that combining non-myeloablative conditioning regimen with TKIs starting the day of the transplantation could be safe.

  1. klf2ash317 Mutant Zebrafish Do Not Recapitulate Morpholino-Induced Vascular and Haematopoietic Phenotypes.

    Directory of Open Access Journals (Sweden)

    Peter Novodvorsky

    Full Text Available The zinc-finger transcription factor Krϋppel-like factor 2 (KLF2 transduces blood flow into molecular signals responsible for a wide range of responses within the vasculature. KLF2 maintains a healthy, quiescent endothelial phenotype. Previous studies report a range of phenotypes following morpholino antisense oligonucleotide-induced klf2a knockdown in zebrafish. Targeted genome editing is an increasingly applied method for functional assessment of candidate genes. We therefore generated a stable klf2a mutant zebrafish and characterised its cardiovascular and haematopoietic development.Using Transcription Activator-Like Effector Nucleases (TALEN we generated a klf2a mutant (klf2ash317 with a 14bp deletion leading to a premature stop codon in exon 2. Western blotting confirmed loss of wild type Klf2a protein and the presence of a truncated protein in klf2ash317 mutants. Homozygous klf2ash317 mutants exhibit no defects in vascular patterning, survive to adulthood and are fertile, without displaying previously described morphant phenotypes such as high-output cardiac failure, reduced haematopoetic stem cell (HSC development or impaired formation of the 5th accessory aortic arch. Homozygous klf2ash317 mutation did not reduce angiogenesis in zebrafish with homozygous mutations in von Hippel Lindau (vhl, a form of angiogenesis that is dependent on blood flow. We examined expression of three klf family members in wildtype and klf2ash317 zebrafish. We detected vascular expression of klf2b (but not klf4a or biklf/klf4b/klf17 in wildtypes but found no differences in expression that might account for the lack of phenotype in klf2ash317 mutants. klf2b morpholino knockdown did not affect heart rate or impair formation of the 5th accessory aortic arch in either wildtypes or klf2ash317 mutants.The klf2ash317 mutation produces a truncated Klf2a protein but, unlike morpholino induced klf2a knockdown, does not affect cardiovascular development.

  2. File list: Pol.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 RNA polymerase Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  3. File list: DNS.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 DNase-seq Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  4. File list: DNS.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 DNase-seq Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  5. File list: Unc.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 Unclassified Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  6. File list: DNS.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 DNase-seq Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  7. File list: Unc.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 Unclassified Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  8. File list: Oth.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 TFs and others Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  9. File list: Unc.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 Unclassified Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  10. File list: Pol.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 RNA polymerase Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  11. File list: InP.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 Input control Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  12. File list: InP.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 Input control Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  13. File list: InP.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 Input control Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  14. File list: Oth.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 TFs and others Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  15. File list: NoD.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 No description Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  16. File list: Unc.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 Unclassified Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  17. File list: Oth.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 TFs and others Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  18. File list: Pol.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 RNA polymerase Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  19. File list: Pol.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 RNA polymerase Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  20. File list: DNS.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 DNase-seq Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  1. File list: NoD.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 No description Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  2. File list: Oth.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 TFs and others Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  3. File list: NoD.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 No description Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  4. File list: NoD.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 No description Blood Granulocyte-Macro...phage Progenitor Cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  5. Number of endothelia progenitor cells from peripheral blood in patients with sudden sensorineural hearing loss%突发性耳聋患者外周血内皮祖细胞的变化

    Institute of Scientific and Technical Information of China (English)

    杨东; 周慧芳

    2012-01-01

    Objective: To investigate the number of endothelia progenitor cells (EPCs) from peripheral blood in patients with sudden sensorineural hearing loss(SSHL) and the proliferative number of EPCs colonies. Methods: Number of EPCs from peripheral blood and number of proliferative colonies of EPCs after 7 d were measured and comparison was made between SSHL group and the healthy group. Results: The number of EPCs reduced significantly in SSHL group compared with contrast group, they were (36.5?.58)/200xl03 cells and(85.3?.55)/200xl03 cells respectively. The number of proliferative colonies of EPCs were(2.01?.31) in SSHL group and (3.80眑.05) in normal group (P?0.01). Conclusion: Because the number of EPCs and the number of proliferative colonies of EPCs significantly lessen in patients with SSHL, EPCs cannot satisfy the body requirement during the process of restoration and result in the symptom of hearing loss.%目的:探讨突发性耳聋患者外周血中内皮祖细胞(EPCs)数量变化及增殖集落变化情况.方法:测定突发性耳聋患者和听力正常健康人外周血中EPCs数量及培养7d后增殖集落数量.结果:突发性耳聋组外周血中EPCs计数为(36.5±2.58)个/20万单个核细胞,听力正常健康人EPCs计数为(85.3±6.55)个/20万单个核细胞,EPCs增殖集落计数分别为(2.01±0.31)个和(3.80±1.05)个,两者比较差异具有统计学意义(P<0.01).结论:突发性耳聋患者由于EPCs数量及增殖集落数量下降,在机体修复过程中不能满足要求而引起耳聋等临床症状.

  6. The glucocorticoid receptor cooperates with the erythropoietin receptor and c-Kit to enhance and sustain proliferation of erythroid progenitors in vitro

    NARCIS (Netherlands)

    W. Zauner; G. Mellitzer; P. Steinlein (Peter); G. Fritsch; K. Huber; H. Beug (Hartmut); B. Löwenberg (Bob); M.M. von Lindern (Marieke)

    1999-01-01

    textabstractAlthough erythropoietin (Epo) is essential for the production of mature red blood cells, the cooperation with other factors is required for a proper balance between progenitor proliferation and differentiation. In avian erythroid progenitors, steroid hormone

  7. GRB Progenitors and Environment

    OpenAIRE

    Lazzati, Davide

    2005-01-01

    The study and knowledge of the environment of Gamma-Ray Bursts is of great interest from many points of view. For high redshift (z>0.5) events, the structure of the ambient medium is one of the best indicators of the nature and properties of the progenitor. It also tells us about the last stages of the pre-explosion evolution of the progenitor. In addition, it is interesting in its own as a sample of the interstellar medium in a high redshift galaxy. Measures of the density and structure of t...

  8. Urological management (medical and surgical of BK-virus associated haemorrhagic cystitis in children following haematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Nikhil Vasdev

    2013-10-01

    Full Text Available Aim: Haemorrhagic cystitis (HC is uncommon and in its severe form potentially life threatening complication of Haematopoietic stem cell transplantation (HSCT in children. We present our single centre experience in the urological management of this clinically challenging condition. Patients and Methods: Fourteen patients were diagnosed with BK-Virus HC in our centre. The mean age at diagnosis was 8.8 years (range, 3.2-18.4 years. The mean number of days post-BMT until onset of HC was 20.8 (range, 1 – 51. While all patients tested urine positive for BKV at the clinical onset of HC, only four patients had viral quantification, with viral loads ranging from 97,000 to >1 billion/ml. 8 patients had clinical HC. Ten patients experienced acute GVHD (grade I: 6 patients, grade II: 3 patients, grade 4: 1 patient.Results: Four patients received medical management for their HC. Treatments included hyperhydration, MESNA, blood and platelet transfusion, premarin and oxybutynin (Table 6.  Two patients received both medical and surgical management which included cystoscopy with clot evacuation, bladder irrigation and supra-pubic catheter insertion. One patient received exclusive surgical management. Seven patients were treated conservatively. Conclusion: There is limited available evidence for other potential therapeutic strategies highlighting the need for more research into the pathophysiology of HSCT-associated HC. Commonly used interventions with possible clinical benefit (e.g. cidofovir, ciprofloxacin still require to be evaluated in multi-centre, high-quality studies. Potential future preventative and therapeutic options, such as modulation of conditioning, immunosuppression and engraftment, new antiviral and anti-inflammatory and less nephrotoxic agents need to be assessed.---------------------------Cite this article as:Vasdev N, Davidson A, Harkensee C, Slatter M, Gennery A, Willetts I, Thorpe A.Urological management (medical and surgical of BK

  9. A survey of fertility and sexual health following allogeneic haematopoietic stem cell transplantation in New South Wales, Australia.

    Science.gov (United States)

    Dyer, Gemma; Gilroy, Nicole; Bradford, Jennifer; Brice, Lisa; Kabir, Masura; Greenwood, Matt; Larsen, Stephen R; Moore, John; Hertzberg, Mark; Kwan, John; Brown, Louisa; Hogg, Megan; Huang, Gillian; Tan, Jeff; Ward, Christopher; Kerridge, Ian

    2016-02-01

    Four hundred and twenty-one adult allogeneic haematopoietic stem cell transplant (HSCT) survivors participated in a cross-sectional study to assess sexual dysfunction and infertility post-transplant. Survey instruments included the Sydney Post-Blood and Marrow Transplant (BMT) Survey, Functional Assessment of Cancer Treatment (FACT) - BMT, the Depression, Anxiety, Stress Scales (DASS 21), the Chronic Graft-versus-Host Disease (cGVHD) Activity Assessment- Patient Self Report (Form B), the Lee cGVHD Symptom Scale and The Post-Traumatic Growth Inventory. Most HSCT survivors reported sexual difficulties (51% of males; 66% of females). Men reported erectile dysfunction (79%) and decreased libido (61·6%) and women reported loss of libido (83%), painful intercourse (73%) and less enjoyment of sex (68%). Women also commonly reported vaginal dryness (73%), vaginal narrowing (34%) and vaginal irritation (26%). Woman had much higher rates of genital cGvHD than men (22% vs. 5%). Age and cGVHD were significantly associated with sexual dysfunction. Few survivors had children following transplant (3·3%). However, for those of reproductive age at HSCT, 22% reported trying to conceive, with 10·3% reporting success. This study is the largest to date exploring sexual function in survivors of allo-HSCT. This data provides the basis for health service reform to better meet the needs of HSCT survivors, including evidence to support counselling and education both pre- and post-transplant. PMID:26847746

  10. Quantification of circulating endothelial progenitor cells using the modified ISHAGE protocol.

    Directory of Open Access Journals (Sweden)

    Caroline Schmidt-Lucke

    Full Text Available AIMS: Circulating endothelial progenitor cells (EPC, involved in endothelial regeneration, neovascularisation, and determination of prognosis in cardiovascular disease can be characterised with functional assays or using immunofluorescence and flow cytometry. Combinations of markers, including CD34+KDR+ or CD133+KDR+, are used. This approach, however may not consider all characteristics of EPC. The lack of a standardised protocol with regards to reagents and gating strategies may account for the widespread inter-laboratory variations in quantification of EPC. We, therefore developed a novel protocol adapted from the standardised so-called ISHAGE protocol for enumeration of haematopoietic stem cells to enable comparison of clinical and laboratory data. METHODS AND RESULTS: In 25 control subjects, 65 patients with coronary artery disease (CAD; 40 stable CAD, 25 acute coronary syndrome/acute myocardial infarction (ACS, EPC were quantified using the following approach: Whole blood was incubated with CD45, KDR, and CD34. The ISHAGE sequential strategy was used, and finally, CD45(dimCD34(+ cells were quantified for KDR. A minimum of 100 CD34(+ events were collected. For comparison, CD45(+CD34(+ and CD45(-CD34(+ were analysed simultaneously. The number of CD45(dimCD34(+KDR(+ cells only were significantly higher in healthy controls compared to patients with CAD or ACS (p = 0.005 each, p<0.001 for trend. An inverse correlation of CD45(dimCD34(+KDR(+ with disease activity (r = -0.475, p<0.001 was confirmed. Only CD45(dimCD34(+KDR(+ correlated inversely with the number of diseased coronaries (r = -0.344; p<0.005. In a second study, a 4-week de-novo treatment of atorvastatin in stable CAD evoked an increase only of CD45(dimCD34(+KDR(+ EPC (p<0.05. CD45(+CD34(+KDR(+ and CD45(-CD34(+KDR(+ were indifferent between the three groups. CONCLUSION: Our newly established protocol adopted from the standardised ISHAGE protocol achieved higher accuracy in

  11. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

    OpenAIRE

    Méndez-Ferrer, Simón; Michurina, Tatyana V.; Ferraro, Francesca; Amin R Mazloom; MacArthur, Ben D; Lira, Sergio A.; Scadden, David T.; Ma’ayan, Avi; Enikolopov, Grigori N.; Frenette, Paul S.

    2010-01-01

    The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin+ MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent ‘mesenspheres’ that can self-renew and expand in serial tr...

  12. Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development ☆

    OpenAIRE

    M.T. Abd El Aziz; Abd El Nabi, E.A.; Abd El Hamid, M.; D. Sabry; Atta, H.M.; L.A. Rahed; A. Shamaa; Mahfouz, S.; Taha, F.M.; S. Elrefaay; Gharib, D.M.; Elsetohy, Khaled A

    2013-01-01

    We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-...

  13. Concise review: programming human pluripotent stem cells into blood.

    Science.gov (United States)

    Easterbrook, Jennifer; Fidanza, Antonella; Forrester, Lesley M

    2016-06-01

    Blood disorders are treated with cell therapies including haematopoietic stem cell (HSC) transplantation as well as platelet and red blood cell transfusions. However the source of cells is entirely dependent on donors, procedures are susceptible to transfusion-transmitted infections and serious complications can arise in recipients due to immunological incompatibility. These problems could be alleviated if it was possible to produce haematopoietic cells in vitro from an autologous and renewable cell source. The production of haematopoietic cells in the laboratory from human induced pluripotent stem cells (iPSCs) may provide a route to realize this goal but it has proven challenging to generate long-term reconstituting HSCs. To date, the optimization of differentiation protocols has mostly relied on the manipulation of extrinsic signals to mimic the in vivo environment. We review studies that have taken an alternative approach to modulate intrinsic signals by enforced expression of transcription factors. Single and combinations of multiple transcription factors have been used in a variety of contexts to enhance the production of haematopoietic cells from human pluripotent stem cells. This programming approach, together with the recent advances in the production and use of synthetic transcription factors, holds great promise for the production of fully functional HSCs in the future. PMID:26996518

  14. Concise review: programming human pluripotent stem cells into blood.

    Science.gov (United States)

    Easterbrook, Jennifer; Fidanza, Antonella; Forrester, Lesley M

    2016-06-01

    Blood disorders are treated with cell therapies including haematopoietic stem cell (HSC) transplantation as well as platelet and red blood cell transfusions. However the source of cells is entirely dependent on donors, procedures are susceptible to transfusion-transmitted infections and serious complications can arise in recipients due to immunological incompatibility. These problems could be alleviated if it was possible to produce haematopoietic cells in vitro from an autologous and renewable cell source. The production of haematopoietic cells in the laboratory from human induced pluripotent stem cells (iPSCs) may provide a route to realize this goal but it has proven challenging to generate long-term reconstituting HSCs. To date, the optimization of differentiation protocols has mostly relied on the manipulation of extrinsic signals to mimic the in vivo environment. We review studies that have taken an alternative approach to modulate intrinsic signals by enforced expression of transcription factors. Single and combinations of multiple transcription factors have been used in a variety of contexts to enhance the production of haematopoietic cells from human pluripotent stem cells. This programming approach, together with the recent advances in the production and use of synthetic transcription factors, holds great promise for the production of fully functional HSCs in the future.

  15. Haematopoietic depletion in vaccine-induced neonatal pancytopenia depends on both the titre and specificity of alloantibody and levels of MHC I expression.

    Science.gov (United States)

    Bell, Charlotte R; MacHugh, Niall D; Connelley, Timothy K; Degnan, Kathryn; Morrison, W Ivan

    2015-07-01

    Bovine Neonatal Pancytopenia (BNP) is a disease of calves characterised by haematopoietic depletion, mediated by ingestion of alloantibodies in colostrum. It has been linked epidemiologically to vaccination of the dams of affected calves with a particular vaccine (Pregsure) containing a novel adjuvant. Evidence suggests that BNP-alloantibodies are directed against MHC I molecules, induced by contaminant bovine cellular material from Madin-Darby Bovine Kidney (MDBK) cells used in the vaccine's production. We aimed to investigate the specificity of BNP-alloantibody for bovine MHC I alleles, particularly those expressed by MDBK cells, and whether depletion of particular cell types is due to differential MHC I expression levels. A complement-mediated cytotoxicity assay was used to assess functional serum alloantibody titres in BNP-dams, Pregsure-vaccinated dams with healthy calves, cows vaccinated with an alternative product and unvaccinated controls. Alloantibody specificity was investigated using transfected mouse lines expressing the individual MHC I alleles identified from MDBK cells and MHC I-defined bovine leukocyte lines. All BNP-dams and 50% of Pregsure-vaccinated cows were shown to have MDBK-MHC I specific alloantibodies, which cross-reacted to varying degrees with other MHC I genotypes. MHC I expression levels on different blood cell types, assessed by flow cytometry, were found to correlate with levels of alloantibody-mediated damage in vitro and in vivo. Alloantibody-killed bone marrow cells were shown to express higher levels of MHC I than undamaged cells. The results provide evidence that MHC I-specific alloantibodies play a dominant role in the pathogenesis of BNP. Haematopoietic depletion was shown to be dependent on the titre and specificity of alloantibody produced by individual cows and the density of surface MHC I expression by different cell types. Collectively, the results support the hypothesis that MHC I molecules originating from MDBK cells

  16. Effects of high glucose on biological characteristics of smooth muscle progenitor cells from human peripheral blood%高糖对成人外周血平滑肌祖细胞功能的影响

    Institute of Scientific and Technical Information of China (English)

    周学凯; 倪旭东; 李飞; 张荣庆; 郭文怡

    2011-01-01

    目的 观察不同浓度葡萄糖对体外培养成人外周血平滑肌祖细胞(smooth muscle progenitor cells,SPCs)增殖、迁移和黏附能力的影响。方法 采用密度梯度离心法从健康成人外周血获取单个核细胞,培养12 d后,采用流式细胞仪对诱导扩增的SPCs进行分析鉴定并分选纯化。间接免疫荧光染色法观察SPCs培养到第28天后人平滑肌细胞特异性肌动蛋白(α-SMA)的表达情况。收集培养第12天的SPCs,随机(补充具体的随机方法?)分为5组并给予不同浓度葡萄糖干预:对照组(5.5 mmol/L),11mmol/L组,22 mmol/L组,44mmol/L组和渗透压对照组(5.5 mmol/L葡萄糖加38 mmol/L甘露醇)。分别用噻唑蓝(methyl thiazolyl tetrazolium,MTT)比色法,Transwell小室迁移实验以及黏附能力测定实验检测各组干预6 d后SPCs增殖、迁移和黏附能力的变化。此外,培养SPCs 8 d,期间用22 mmol/L葡萄糖分别干预0、2、4、8 d,观察各组细胞增殖、迁移和黏附能力的变化。结果 与对照组相比,高糖各组均能明显促进外周血SPCs的增殖、迁移和黏附能力,其中22 mmol/L葡萄糖组的影响最为显著,44mmol/L葡萄糖组的促进作用有所下降。用22 mmol/L葡萄糖分别干预SPCs 0、2、4、8 d,其增殖、迁移和黏附能力随着作用时间延长而增强,以干预8 d组最显著。结论 高糖能在一定范围内增强外周血SPCs的增殖、迁移、黏附能力,随着浓度增加和时间延长,作用更明显。推测长期高血糖通过促进SPCs的功能参与受损血管过度修复,引起部分心血管疾病的发生发展。%Objectives To investigate the effects of high glucose on proliferation, migration and adhesion of smooth muscle progenitor cells ( SPCs ) in vitro. Methods Mononuclear cells were isolated from adult collected peripheral blood by density gradient centrifugation and cultured. After 12 days of culture in vitro,SPCs were identified

  17. Isoform-specific potentiation of stem and progenitor cell engraftment by AML1/RUNX1.

    OpenAIRE

    Shinobu Tsuzuki; Dengli Hong; Rajeev Gupta; Keitaro Matsuo; Masao Seto; Tariq Enver

    2007-01-01

    Editors' Summary Background. Blood contains red blood cells (which carry oxygen round the body), platelets (which help the blood to clot), and white blood cells (which fight off infections). All these cells, which are regularly replaced, are derived from hematopoietic stem cells, blood-forming cells present in the bone marrow. Like all stem cells, hematopoietic stem cells self-renew (reproduce themselves) and produce committed progenitor cells, which develop into mature blood cells in a proce...

  18. A Progenitor Cell Expressing Transcription Factor RORγt Generates All Human Innate Lymphoid Cell Subsets.

    Science.gov (United States)

    Scoville, Steven D; Mundy-Bosse, Bethany L; Zhang, Michael H; Chen, Li; Zhang, Xiaoli; Keller, Karen A; Hughes, Tiffany; Chen, Luxi; Cheng, Stephanie; Bergin, Stephen M; Mao, Hsiaoyin C; McClory, Susan; Yu, Jianhua; Carson, William E; Caligiuri, Michael A; Freud, Aharon G

    2016-05-17

    The current model of murine innate lymphoid cell (ILC) development holds that mouse ILCs are derived downstream of the common lymphoid progenitor through lineage-restricted progenitors. However, corresponding lineage-restricted progenitors in humans have yet to be discovered. Here we identified a progenitor population in human secondary lymphoid tissues (SLTs) that expressed the transcription factor RORγt and was unique in its ability to generate all known ILC subsets, including natural killer (NK) cells, but not other leukocyte populations. In contrast to murine fate-mapping data, which indicate that only ILC3s express Rorγt, these human progenitor cells as well as human peripheral blood NK cells and all mature ILC populations expressed RORγt. Thus, all human ILCs can be generated through an RORγt(+) developmental pathway from a common progenitor in SLTs. These findings help establish the developmental signals and pathways involved in human ILC development.

  19. Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors

    DEFF Research Database (Denmark)

    Paul, Franziska; Arkin, Ya'ara; Giladi, Amir;

    2015-01-01

    Within the bone marrow, stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with in vivo differentiation potential or gene regulatory m...

  20. Socially disadvantaged parents of children treated with allogeneic haematopoietic stem cell transplantation (HSCT)

    DEFF Research Database (Denmark)

    Larsen, Hanne Bækgaard; Heilmann, Carsten; Johansen, Christoffer;

    2013-01-01

    PURPOSE: This study was undertaken to test a daily Family Navigator Nurse (FNN) conducted intervention program, to support parents during the distressful experience of their child's Allogeneic Haematopoietic Stem Cell Transplantation (HSCT). METHODS: A qualitative analysis of the supportive......: Three main problems faced by all parents included 1) the emotional strain of the child's HSCT; 2) re-organizing of the family's daily life to include hospitalization with the child; and 3) the financial strain of manoeuvring within the Danish welfare system. The FNN performed daily intervention rounds...

  1. An isolate and sequence database of infectious haematopoietic necrosis virus (IHNV)

    DEFF Research Database (Denmark)

    Jonstrup, Søren Peter; Schuetze, H.; Kurath, G.;

    2010-01-01

    In the field of fish diseases, the amount of relevant information available is enormous. Internet-based databases are an excellent tool for keeping track of the available knowledge in the field. Fishpathogens.eu was launched in June 2009 with the aim of collecting, storing and sorting data on fish...... pathogens. The first pathogen to be included was the rhabdovirus, viral haemorrhagic septicaemia virus (VHSV). Here, we present an extension of the database to also include infectious haematopoietic necrosis virus (IHNV). The database is developed, maintained and managed by the European Community Reference...

  2. From progenitor to afterlife

    CERN Document Server

    Chevalier, R A

    2006-01-01

    The sequence of massive star supernova types IIP (plateau light curve), IIL (linear light curve), IIb, IIn (narrow line), Ib, and Ic roughly represents a sequence of increasing mass loss during the stellar evolution. The mass loss affects the velocity distribution of the ejecta composition; in particular, only the IIP's typically end up with H moving at low velocity. Radio and X-ray observations of extragalactic supernovae show varying mass loss properties that are in line with expectations for the progenitor stars. For young supernova remnants, pulsar wind nebulae and circumstellar interaction provide probes of the inner ejecta and higher velocity ejecta, respectively. Among the young remnants, there is evidence for supernovae over a range of types, including those that exploded with much of the H envelope present (Crab Nebula, 3C 58, 0540--69) and those that exploded after having lost most of their H envelope (Cas A, G292.0+1.8).

  3. Manganese effects on haematopoietic cells and circulating coelomocytes of Asterias rubens (Linnaeus)

    Energy Technology Data Exchange (ETDEWEB)

    Oweson, Carolina; Skoeld, Helen [Department of Marine Ecology, Goeteborg University, Kristineberg 566, 45034 Fiskebaeckskil (Sweden); Pinsino, Annalisa; Matranga, Valeria [Istituto di Biomedicina e Immunologia Molecolare ' A. Monroy' , Via Ugo La Malfa 153, 90146 Palermo (Italy); Hernroth, Bodil [The Royal Swedish Academy of Sciences, Kristineberg 566, 45034 Fiskebaeckskil (Sweden)], E-mail: bodil.hernroth@marecol.gu.se

    2008-08-29

    Manganese (Mn) is a naturally abundant metal in marine sediments where it mainly occurs as MnO{sub 2}. During hypoxic conditions it is converted into a bioavailable state, Mn{sup 2+}, and can reach levels that previously have shown effects on immune competent cells of the crustacean, Nephrops norvegicus. Here we investigated if Mn also affects circulating coelomocytes and their renewal in the common sea star, Asterias rubens, when exposed to concentrations of Mn that can be found in nature. When the sea stars were exposed to Mn it accumulated in the coelomic fluid and the number of circulating coelomocytes, in contrast to what was recorded in Nephrops, increased significantly. By using the substitute nucleotide, 5-bromo-2'-deoxyuridine, BrdU, for tracing cell division and by recording mitotic index by nuclei staining, we found that Mn induced proliferation of cells from a putative haematopoietic tissue, the coelomic epithelium. In addition, the haematopoietic tissue and coelomocytes showed stress response in terms of changes in HSP70 levels and protein carbonyls, as judged by immunohistochemistry and Western blotting. Measurement of dehydrogenase activity, using MTS/PMS, revealed that Mn showed cytotoxic properties. We also found that the phagocytotic capacity of coelomocytes was significantly inhibited by Mn. It was concluded that the exposure of A. rubens to Mn induced renewal of coelomocytes and impaired their immune response.

  4. PRMT4 is a novel coactivator of c-Myb-dependent transcription in haematopoietic cell lines.

    Directory of Open Access Journals (Sweden)

    Gundula Streubel

    Full Text Available Protein arginine methyltransferase 4 (PRMT4-dependent methylation of arginine residues in histones and other chromatin-associated proteins plays an important role in the regulation of gene expression. However, the exact mechanism of how PRMT4 activates transcription remains elusive. Here, we identify the chromatin remodeller Mi2α as a novel interaction partner of PRMT4. PRMT4 binds Mi2α and its close relative Mi2β, but not the other components of the repressive Mi2-containing NuRD complex. In the search for the biological role of this interaction, we find that PRMT4 and Mi2α/β interact with the transcription factor c-Myb and cooperatively coactivate c-Myb target gene expression in haematopoietic cell lines. This coactivation requires the methyltransferase and ATPase activity of PRMT4 and Mi2, respectively. Chromatin immunoprecipitation analysis shows that c-Myb target genes are direct transcriptional targets of PRMT4 and Mi2. Knockdown of PRMT4 or Mi2α/β in haematopoietic cells of the erythroid lineage results in diminished transcriptional induction of c-Myb target genes, attenuated cell growth and survival, and deregulated differentiation resembling the effects caused by c-Myb depletion. These findings reveal an important and so far unknown connection between PRMT4 and the chromatin remodeller Mi2 in c-Myb signalling.

  5. Autografting of peripheral-blood progenitor cells early in chronic myeloid Leukemia Transplante autólogo de células progenitoras em fase crônica precoce da Leucemia mielóide crônica

    Directory of Open Access Journals (Sweden)

    Paulo V. B. Carvalho

    2004-12-01

    Full Text Available The role of peripheral-blood progenitor cell (PBPC transplantation as a treatment for chronic myeloid leukemia (CML patients remains uncertain. We presented herein 11 CML patients treated with autografting of PBPC in early chronic phase followed by interferon-alpha (IFN-alpha. Bone marrow samples obtained at diagnosis and during follow-up after autografting as well as leukapheresis products were analyzed by cytogenetics, fluorescence in situ hybridization (FISH and reverse transcriptase-polymerase chain reaction (RT-PCR. The median follow-up of patients after autografting was 22 months (range: 1-49. Two treatment-related deaths occurred in patients enrolled in the study. Eight out of 9 (88.9% and 7 out of 9 (77.8% patients achieved hematologic and cytogenetic responses, respectively. Molecular cytogenetic and molecular responses were seen in all 7 patients analyzed (100.0% and in one single patient (11.1%, respectively. The median percentages of Ph+ (78.0% metaphases obtained after 6 months of autografting was lower than those obtained at diagnosis (100.0%, P=0.04. The median percentages of FISH+ nuclei obtained at 3 (4.0%, 6 (7.3% and 9 (14.7% months after autografting were also lower than that obtained at diagnosis (82.5%; P=0.002; P=0.003; P=0.030, respectively. At the end of the study, 9 patients (81.8% were alive in chronic phase, 4 of them presenting hematologic, cytogenetic and molecular cytogenetic responses. We conclude that autografting performed with PBPC in early chronic phase of CML followed by IFN-alpha results in lower numbers of Ph+ and FISH+ cells in bone marrow.O papel do transplante de célula progenitora periférica (CPP como tratamento de pacientes com leucemia mielóide crônica (LMC permanece incerto. Nós apresentamos neste estudo 11 pacientes com LMC tratados com o transplante autólogo (TMO-auto de CPP durante a fase crônica precoce, seguido de interferon-alfalfa (IFN-alfa. Amostras de medula óssea, obtidas ao diagn

  6. Biological behaviour and role of endothelial progenitor cells in vascular diseases

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qiu-hua; SHE Ming-peng

    2007-01-01

    Obiective To review the biological behaviour of endothelial progenitor cells and their role in vascular diseases.Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1985 to March 2007.The search term was "endothelial progenitor cells".Study selection Articles about the biological behaviour of endothelial progenitor cells and their roles in the pathogenesis of vascular diseases such as atherogenesis were used.Results Progenitor cells in bone marrow,peripheral blood and adventitia can differentiate into mature endothelial cells (ECs).The progenitor cells,which express certain surface markers including AC133,CD34 and KDR,enable restoration of the microcirculation and ECs when injury or ischaemia occurs.Endothelial progenitor cells used in experimental models and clinical trials for ischaemic syndromes could restore endothelial integrity and inhibit neointima development.Moreover,their number and functional properties are influenced by certain cytokines and atherosclerotic risk factors.Impairment of the progenitor cells might limit the regenerative capacity,even lead to the development of atherosclerosis or other vascular diseases.Conclusions Endothelial progenitor cells have a particular role in prevention and treatment of certain cardiovascular diseases.However,many challenges remain in understanding differentiation of endothelial progenitor cells,their mobilization and revascularization.

  7. Effect of endothelial progenitor cells in neovascularization and their application in tumor therapy

    Institute of Scientific and Technical Information of China (English)

    DONG Fang; HA Xiao-qin

    2010-01-01

    Objective To review the effect of endothelial progenitor cells in neovascularization as well as their application to the therapy of tumors.Data sources The data used in this review were mainly from PubMed for relevant English language articles published from 1997 to 2009. The search term was "endothelial progenitor cells".Study selection Articles regarding the role of endothelial progenitor cells in neovascularization and their application to the therapy of tumors were selected.Results Endothelial progenitor cells isolated from bone marrow, umbilical cord blood and peripheral blood can proliferate, mobilize and differentiate into mature endothelial cells. Experiments suggest endothelial progenitor cells take part in forming the tumor vascular through a variety of mechanisms related to vascular endothelial growth factor, matrix metalloproteinases, chemokine stromal cell-derived factor 1 and its receptor C-X-C receptor-4, erythropoietin, Notchsignal pathway and so on. Evidence demonstrates that the number and function change of endothelial progenitor cells in peripheral blood can be used as a biomarker of the response of cancer patients to anti-tumor therapy and predict the prognosis and recurrence. In addition, irradiation temporarily increased endothelial cells number and decreased the endothelial progenitor cell counts in animal models. Meanwhile, in preclinical experiments, therapeutic gene-modified endothelial progenitor cells have been approved to attenuate tumor growth and offer a novel strategy for cell therapy and gene therapy of cancer.Conclusions Endothelial progenitor cells play a particular role in neovascularization and have attractively potential prognostic and therapeutic applications to malignant tumors. However, a series of problems, such as the definitive biomarkers of endothelial progenitor cells, their interrelationship with radiotherapy and their application in cell therapy and gene therapy of tumors, need further investigation.

  8. Spinal osteomyelitis due to Aspergillus flavus in a child: a rare complication after haematopoietic stem cell transplantation

    International Nuclear Information System (INIS)

    We report the case of a child affected by acute myeloid leukaemia who was treated with allogeneic haematopoietic stem cell transplantation and developed cervicothoracic spinal osteomyelitis due to Aspergillus flavus. The diagnosis was difficult on a clinical basis, but made possible by conventional radiography and MRI. (orig.)

  9. Spinal osteomyelitis due to Aspergillus flavus in a child: a rare complication after haematopoietic stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Beluffi, Giampiero [Fondazione IRCCS Policlinico ' S.Matteo' , Section of Paediatric Radiology, Department of Radiodiagnosis, Pavia PV (Italy); Bernardo, Maria E.; Locatelli, Franco [University of Pavia, Fondazione IRCCS Policlinico ' S.Matteo' , Department of Paediatric Haematology/Oncology, Pavia (Italy); Meloni, Giulia [University of Pavia, Fondazione IRCCS Policlinico ' S.Matteo' , Institute of Radiology, Pavia (Italy); Spinazzola, Angelo [Fondazione IRCCS Policlinico ' S.Matteo' , Section of Paediatric Radiology, Department of Radiodiagnosis, Pavia PV (Italy); Ospedale Maggiore, Crema CR (Italy)

    2008-06-15

    We report the case of a child affected by acute myeloid leukaemia who was treated with allogeneic haematopoietic stem cell transplantation and developed cervicothoracic spinal osteomyelitis due to Aspergillus flavus. The diagnosis was difficult on a clinical basis, but made possible by conventional radiography and MRI. (orig.)

  10. Selective in vitro expansion and efficient retroviral transduction of human CD34(+) CD38(-) haematopoietic stem cells

    NARCIS (Netherlands)

    Ng, YY; Bloem, AC; van Kessel, B; Lokhorst, H; Logtenberg, T; Staal, FJT

    2002-01-01

    Ex vivo expansion of primitive human haematopoietic stem cells (HSC) is clinically relevant for stem cell transplantation and gene therapy. Here, we demonstrate the selective expansion of CD34(+) CD38(-) cells from purified CD34(+) cells upon stimulation with Flt3-ligand, stem cell factor and thromb

  11. How to improve the search for an unrelated haematopoietic stem cell donor. Faster is better than more!

    NARCIS (Netherlands)

    Heemskerk, MBA; van Walraven, SM; Cornelissen, JJ; Barge, RMY; Bredius, RGM; Egeler, RM; Lie, JLWT; Revesz, T; Sintnicolaas, K; Wulffraat, NM; Donker, AE; Hoogerbrugge, PM; van Rood, JJ; Claas, FHJ; Oudshoorn, M

    2005-01-01

    Many patients do not reach haematopoietic stem cell transplantation. Shortage of unrelated donors (UDs) is still seen as the main cause. However, with a worldwide UD pool containing more than 8 million donors, it is possible that other impediments are becoming more important. We analysed 549 UD sear

  12. Progenitors of type Ia supernovae

    CERN Document Server

    Maeda, Keiichi

    2016-01-01

    Natures of progenitors of type Ia Supernovae (SNe Ia) have not yet been clarified. There has been long and intensive discussion on whether the so-called single degenerate (SD) scenario or the double degenerate (DD) scenario, or anything else, could explain a major population of SNe Ia, but the conclusion has not yet been reached. With rapidly increasing observational data and new theoretical ideas, the field of studying the SN Ia progenitors has been quickly developing, and various new insights have been obtained in recent years. This article aims at providing a summary of the current situation regarding the SN Ia progenitors, both in theory and observations. It seems difficult to explain the emerging diversity seen in observations of SNe Ia by a single population, and we emphasize that it is important to clarify links between different progenitor scenarios and different sub-classes of SNe Ia.

  13. Thrombotic thrombocytopenic purpura after allogeneic stem cell transplantation : a survey of the European Group for Blood and Marrow Transplantation (EBMT)

    NARCIS (Netherlands)

    Ruutu, T; Hermans, J; Niederwieser, D; Gratwohl, A; Kiehl, M; Volin, L; Bertz, H; Ljungman, P; Spence, D; Verdonck, LF; Prentice, HG; Bosi, A; du Toit, CE; Brinch, L; Apperley, JF

    2002-01-01

    A survey was carried out among the European Group for Blood and Marrow Transplantation (EBMT) centres to determine the incidence, risk factors, treatment and outcome of thrombotic thrombocytopenic purpura (TTP) following allogeneic haematopoietic stem cell transplantation. TTP was defined as the sim

  14. Religious perspectives on umbilical cord blood banking.

    Science.gov (United States)

    Jordens, Christopher F C; O'Connor, Michelle A C; Kerridge, Ian H; Stewart, Cameron; Cameron, Andrew; Keown, Damien; Lawrence, Rabbi Jeremy; McGarrity, Andrew; Sachedina, Abdulaziz; Tobin, Bernadette

    2012-03-01

    Umbilical cord blood is a valuable source of haematopoietic stem cells. There is little information about whether religious affiliations have any bearing on attitudes to and decisions about its collection, donation and storage. The authors provided information about umbilical cord blood banking to expert commentators from six major world religions (Catholicism, Anglicanism, Islam, Judaism, Hinduism and Buddhism) and asked them to address a specific set of questions in a commentary. The commentaries suggest there is considerable support for umbilical cord blood banking in these religions. Four commentaries provide moral grounds for favouring public donation over private storage. None attach any particular religious significance to the umbilical cord or to the blood within it, nor place restrictions on the ethnicity or religion of donors and recipients. Views on ownership of umbilical cord blood vary. The authors offer a series of general points for those who seek a better understanding of religious perspectives on umbilical cord blood banking. PMID:22558902

  15. Omega 3 fatty acids reduce myeloid progenitor cell frequency in the bone marrow of mice and promote progenitor cell differentiation

    Directory of Open Access Journals (Sweden)

    Sollars Vincent E

    2009-03-01

    Full Text Available Abstract Background Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias. Results We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts. Conclusion Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.

  16. The level of circulating endothelial progenitor cells may be associated with the occurrence and recurrence of chronic subdural hematoma

    Directory of Open Access Journals (Sweden)

    Yan Song

    2013-01-01

    Full Text Available OBJECTIVES: The onset of chronic subdural hematoma may be associated with direct or indirect minor injuries to the head or a poorly repaired vascular injury. Endothelial progenitor cells happen to be one of the key factors involved in hemostasis and vascular repair. This study was designed to observe the levels of endothelial progenitor cells, white blood cells, platelets, and other indicators in the peripheral blood of patients diagnosed with chronic subdural hematoma to determine the possible relationship between the endothelial progenitor cells and the occurrence, development, and outcomes of chronic subdural hematoma. METHOD: We enrolled 30 patients with diagnosed chronic subdural hematoma by computer tomography scanning and operating procedure at Tianjin Medical University General Hospital from July 2009 to July 2011. Meanwhile, we collected 30 cases of peripheral blood samples from healthy volunteers over the age of 50. Approximately 2 ml of blood was taken from veins of the elbow to test the peripheral blood routine and coagulation function. The content of endothelial progenitor cells in peripheral blood mononuclear cells was determined by flow cytometry. RESULTS: The level of endothelial progenitor cells in peripheral blood was significantly lower in preoperational patients with chronic subdural hematomas than in controls. There were no significant differences between the two groups regarding the blood routine and coagulation function. However, the levels of circulating endothelial progenitor cells were significantly different between the recurrent group and the non-recurrent group. CONCLUSIONS: The level of circulating endothelial progenitor cells in chronic subdural hematoma patients was significantly lower than the level in healthy controls. Meanwhile, the level of endothelial progenitor cells in recurrent patients was significantly lower than the level in patients without recurrence. Endothelial progenitor cells may be related to the

  17. File list: ALL.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 All antigens Blood Granulocyte-Macro...ciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.05.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  18. File list: ALL.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 All antigens Blood Granulocyte-Macro...ciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.20.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  19. File list: ALL.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 All antigens Blood Granulocyte-Macro...ciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.50.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  20. File list: ALL.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells mm9 All antigens Blood Granulocyte-Macro...ciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.10.AllAg.Granulocyte-Macrophage_Progenitor_Cells.bed ...

  1. Growth factor-and cytokine-stimulated endothelial progenitor cells in post-ischemic cerebral neovascularization

    Institute of Scientific and Technical Information of China (English)

    Philip V.Peplow

    2014-01-01

    Endothelial progenitor cells are resident in the bone marrow blood sinusoids and circulate in the peripheral circulation. They mobilize from the bone marrow after vascular injury and home to the site of injury where they differentiate into endothelial cells. Activation and mobilization of endothelial progenitor cells from the bone marrow is induced via the production and release of endothelial progenitor cell-activating factors and includes speciifc growth factors and cytokines in response to peripheral tissue hypoxia such as after acute ischemic stroke or trauma. Endotheli-al progenitor cells migrate and home to speciifc sites following ischemic stroke via growth factor/cytokine gradients. Some growth factors are less stable under acidic conditions of tissue isch-emia, and synthetic analogues that are stable at low pH may provide a more effective therapeutic approach for inducing endothelial progenitor cell mobilization and promoting cerebral neovas-cularization following ischemic stroke.

  2. How much blood is needed?

    Science.gov (United States)

    Seifried, E; Klueter, H; Weidmann, C; Staudenmaier, T; Schrezenmeier, H; Henschler, R; Greinacher, A; Mueller, M M

    2011-01-01

    Demographic changes in developed countries as their populations age lead to a steady increase in the consumption of standard blood components. Complex therapeutic procedures like haematopoietic stem cell transplantation, cardiovascular surgery and solid organ transplantation are options for an increasing proportion of older patients nowadays. This trend is likely to continue in coming years. On the other hand, novel aspects in transplant regimens, therapies for malignant diseases, surgical procedures and perioperative patient management have led to a moderate decrease in blood product consumption per individual procedure. The ageing of populations in developed countries, intra-society changes in the attitude towards blood donation as an important altruistic behaviour and the overall alterations in our societies will lead to a decline in regular blood donations over the next decades in many developed countries. Artificial blood substitutes or in vitro stem cell-derived blood components might also become alternatives in the future. However, such substitutes are still in early stages of development and will therefore probably not alleviate this problem within the next few years. Taken together, a declining donation rate and an increase in the consumption of blood components require novel approaches on both sides of the blood supply chain. Different blood donor groups require specific approaches and, for example, inactive or deferred donors must be re-activated. Optimal use of blood components requires even more attention. PMID:21175652

  3. Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells.

    Science.gov (United States)

    Grover, Amit; Sanjuan-Pla, Alejandra; Thongjuea, Supat; Carrelha, Joana; Giustacchini, Alice; Gambardella, Adriana; Macaulay, Iain; Mancini, Elena; Luis, Tiago C; Mead, Adam; Jacobsen, Sten Eirik W; Nerlov, Claus

    2016-01-01

    Aged haematopoietic stem cells (HSCs) generate more myeloid cells and fewer lymphoid cells compared with young HSCs, contributing to decreased adaptive immunity in aged individuals. However, it is not known how intrinsic changes to HSCs and shifts in the balance between biased HSC subsets each contribute to the altered lineage output. Here, by analysing HSC transcriptomes and HSC function at the single-cell level, we identify increased molecular platelet priming and functional platelet bias as the predominant age-dependent change to HSCs, including a significant increase in a previously unrecognized class of HSCs that exclusively produce platelets. Depletion of HSC platelet programming through loss of the FOG-1 transcription factor is accompanied by increased lymphoid output. Therefore, increased platelet bias may contribute to the age-associated decrease in lymphopoiesis. PMID:27009448

  4. Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells.

    Science.gov (United States)

    Souilhol, Céline; Gonneau, Christèle; Lendinez, Javier G; Batsivari, Antoniana; Rybtsov, Stanislav; Wilson, Heather; Morgado-Palacin, Lucia; Hills, David; Taoudi, Samir; Antonchuk, Jennifer; Zhao, Suling; Medvinsky, Alexander

    2016-01-01

    During embryonic development, adult haematopoietic stem cells (HSCs) emerge preferentially in the ventral domain of the aorta in the aorta-gonad-mesonephros (AGM) region. Several signalling pathways such as Notch, Wnt, Shh and RA are implicated in this process, yet how these interact to regulate the emergence of HSCs has not previously been described in mammals. Using a combination of ex vivo and in vivo approaches, we report here that stage-specific reciprocal dorso-ventral inductive interactions and lateral input from the urogenital ridges are required to drive HSC development in the aorta. Our study strongly suggests that these inductive interactions in the AGM region are mediated by the interplay between spatially polarized signalling pathways. Specifically, Shh produced in the dorsal region of the AGM, stem cell factor in the ventral and lateral regions, and BMP inhibitory signals in the ventral tissue are integral parts of the regulatory system involved in the development of HSCs. PMID:26952187

  5. Patients' experience of sexuality 1-year after allogeneic Haematopoietic Stem Cell Transplantation

    DEFF Research Database (Denmark)

    Nørskov, Kristina H; Schmidt, Mette; Jarden, Mary

    2015-01-01

    body image, which directly or indirectly resulted in sexual dysfunction or problems with intimacy. Symptoms related to chronic GVHD, could explain experiences of sexual dysfunction. Sexual needs were deprioritized as survival became paramount. The experience of changed social roles, both in family life...... and social network, affected self-image and identity. Finally, communication about sexuality and sexual needs was of significant importance to the current state of their relationship. CONCLUSION: Physical body alterations, challenges in mastering their new life situation and identity changes affected......PURPOSE: This study explores how patients' experience of sexuality is influenced by physical, psychological and social changes one year after undergoing haematopoietic stem cell transplantation (HSCT). METHODS: A qualitative study using semi-structured in-depth interviews. The respondents (n = 9...

  6. Hematopoietic stem/progenitor cell commitment to the megakaryocyte lineage.

    Science.gov (United States)

    Woolthuis, Carolien M; Park, Christopher Y

    2016-03-10

    The classical model of hematopoiesis has long held that hematopoietic stem cells (HSCs) sit at the apex of a developmental hierarchy in which HSCs undergo long-term self-renewal while giving rise to cells of all the blood lineages. In this model, self-renewing HSCs progressively lose the capacity for self-renewal as they transit into short-term self-renewing and multipotent progenitor states, with the first major lineage commitment occurring in multipotent progenitors, thus giving rise to progenitors that initiate the myeloid and lymphoid branches of hematopoiesis. Subsequently, within the myeloid lineage, bipotent megakaryocyte-erythrocyte and granulocyte-macrophage progenitors give rise to unipotent progenitors that ultimately give rise to all mature progeny. However, over the past several years, this developmental scheme has been challenged, with the origin of megakaryocyte precursors being one of the most debated subjects. Recent studies have suggested that megakaryocytes can be generated from multiple pathways and that some differentiation pathways do not require transit through a requisite multipotent or bipotent megakaryocyte-erythrocyte progenitor stage. Indeed, some investigators have argued that HSCs contain a subset of cells with biased megakaryocyte potential, with megakaryocytes directly arising from HSCs under steady-state and stress conditions. In this review, we discuss the evidence supporting these nonclassical megakaryocytic differentiation pathways and consider their relative strengths and weaknesses as well as the technical limitations and potential pitfalls in interpreting these studies. Ultimately, such pitfalls will need to be overcome to provide a comprehensive and definitive understanding of megakaryopoiesis. PMID:26787736

  7. The influence of TRP53 in the dose response of radiation-induced apoptosis, DNA repair and genomic stability in murine haematopoietic cells

    International Nuclear Information System (INIS)

    Apoptotic and DNA damage endpoints are frequently used as surrogate markers of cancer risk, and have been well-studied in the Trp53+/- mouse model. We report the effect of differing Trp53 gene status on the dose response of ionizing radiation exposures (0.01-2 Gy), with the unique perspective of determining if effects of gene status remain at extended time points. Here we report no difference in the dose response for radiation-induced DNA double-strand breaks in bone marrow and genomic instability (MN-RET levels) in peripheral blood, between wild-type (Trp53+/+) and heterozygous (Trp53+/-) mice. The dose response for Trp53+/+ mice showed higher initial levels of radiation-induced lymphocyte apoptosis relative to Trp53+/- between 0 and 1 Gy. Although this trend was observed up to 12 hours post-irradiation, both genotypes ultimately reached the same level of apoptosis at 14 hours, suggesting the importance of late-onset p53-independent apoptotic responses in this mouse model. Expected radiation-induced G1 cell cycle delay was observed in Trp53+/+ but not Trp53+/-. Although p53 has an important role in cancer risk, we have shown its influence on radiation dose response can be temporally variable. This research highlights the importance of caution when using haematopoietic endpoints as surrogates to extrapolate radiation-induced cancer risk estimation

  8. Adiponectin promotes endothelial progenitor cell number and function

    OpenAIRE

    Shibata, Rei; Skurk, Carsten; Ouchi, Noriyuki; Galasso, Gennaro; Kondo, Kazuhisa; Ohashi, Taiki; Shimano, Masayuki; Kihara, Shinji; Murohara, Toyoaki; Walsh, Kenneth

    2008-01-01

    Obesity-linked diseases are associated with suppressed endothelial progenitor cell (EPC) function. Adiponectin is an adipose-derived protein that is downregulated in obese and diabetic subjects. Here, we investigated the effects of adiponectin on EPCs. EPC levels did not increase in adiponectin deficient (APN-KO) in response to hindlimb ischemia. Adenovirus-mediated delivery of adiponectin increased EPC levels in both WT and APN-KO mice. Incubation of human peripheral blood mononuclear cells ...

  9. Embryonic Heart Progenitors and Cardiogenesis

    Science.gov (United States)

    Brade, Thomas; Pane, Luna S.; Moretti, Alessandra; Chien, Kenneth R.; Laugwitz, Karl-Ludwig

    2013-01-01

    The mammalian heart is a highly specialized organ, comprised of many different cell types arising from distinct embryonic progenitor populations during cardiogenesis. Three precursor populations have been identified to contribute to different myocytic and nonmyocytic cell lineages of the heart: cardiogenic mesoderm cells (CMC), the proepicardium (PE), and cardiac neural crest cells (CNCCs). This review will focus on molecular cues necessary for proper induction, expansion, and lineage-specific differentiation of these progenitor populations during cardiac development in vivo. Moreover, we will briefly discuss how the knowledge gained on embryonic heart progenitor biology can be used to develop novel therapeutic strategies for the management of congenital heart disease as well as for improvement of cardiac function in ischemic heart disease. PMID:24086063

  10. Generating New Blood Flow : Integrating Developmental Biology and Tissue Engineering

    NARCIS (Netherlands)

    Krenning, Guido; Moonen, Jan-Renier A. J.; van Luyn, Marja J. A.; Harmsen, Martin C.

    2008-01-01

    Vascular tissue engineering aims to restore blood flow by seeding artificial tubular scaffolds with endothelial and smooth muscle cells, thus creating bioartificial blood vessels. Herein, the progenitors of smooth muscle and endothelial cells hold great promise because they efficiently differentiate

  11. Fifteen-year follow-up of a patient with beta thalassaemia and extramedullary haematopoietic tissue compressing the spinal cord

    International Nuclear Information System (INIS)

    A long-term follow-up of a patient with beta thalassaemia with intra- and extraspinal extramedullary haematopoietic tissue compressing the spinal cord is presented. Extramedullary haematopoietic nodules are a rare cause of spinal cord compression and should be included in the differential diagnosis, especially in patients from Mediterranean countries. Treatment with radiation therapy solely failed, giving rise to the need of surgical intervention. Surgical decompression of the spine and the removal of the culprit lesion compressing the spine were performed. Postinterventional radiation therapy was applied to the spine. A relapse had to be treated again by surgical means combined with postinterventional radiation therapy. A complete relief of the symptoms and control of the lesion could be obtained

  12. Fifteen-year follow-up of a patient with beta thalassaemia and extramedullary haematopoietic tissue compressing the spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Niggemann, P.; Krings, T.; Thron, A. [Dept. of Neuroradiology, RWTH-Aachen Hosital (Germany); Hans, F. [Dept. of Neurosurgery, RWTH Aachen Hospital (Germany); 1

    2005-04-01

    A long-term follow-up of a patient with beta thalassaemia with intra- and extraspinal extramedullary haematopoietic tissue compressing the spinal cord is presented. Extramedullary haematopoietic nodules are a rare cause of spinal cord compression and should be included in the differential diagnosis, especially in patients from Mediterranean countries. Treatment with radiation therapy solely failed, giving rise to the need of surgical intervention. Surgical decompression of the spine and the removal of the culprit lesion compressing the spine were performed. Postinterventional radiation therapy was applied to the spine. A relapse had to be treated again by surgical means combined with postinterventional radiation therapy. A complete relief of the symptoms and control of the lesion could be obtained.

  13. A comparison of the observed and the expected cancers of the haematopoietic and lymphatic systems among workers at Windscale

    International Nuclear Information System (INIS)

    Data are given about the cases of cancers of the haematopoietic and lymphatic systems among workers at Windscale Works, BNFL during the period 1950 to 1974. The number of cancers of these types expected to occur in the working population at Windscale has been estimated for the same period. For none of these types is the observed number of cancers significantly different at the 95% confidence level from that expected. (author)

  14. Investigation of immunological approaches to enhance engraftment in a 1 Gy TBI canine haematopoietic stem cell transplantation model

    Science.gov (United States)

    Lange, Sandra; Altmann, Simone; Brandt, Bettina; Adam, Carsten; Riebau, Franziska; Vogel, Heike; Weirich, Volker; Hilgendorf, Inken; Storb, Rainer; Freund, Mathias; Junghanss, Christian

    2010-01-01

    Objective Stable mixed haematopoietic chimerism can be established in a canine stem cell transplantation model using a conditioning consisting of total body irradiation (TBI, 2Gy) and postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporin (CSA). Reduction of TBI had resulted in graft rejection in this model previously. We investigated whether postgrafting stimulation of donor T-cells against recipient’s haematopoietic antigens or graft augmentation with donor monocyte-derived dendritic cells (MoDC) promote engraftment following 1Gy TBI. Methods All dogs received dog leukocyte-antigen-identical bone marrow transplantation. Dogs were conditioned with either 2Gy of TBI (group 1) or 1Gy of TBI followed by repetitive recipient haematopoietic cell lysate vaccinations (group 2) or graft augmentation with MoDC (group 3). Immunosuppression consisted of CSA and MMF. Results In group 1 four animals remained stable chimeras >wk110, and 3 rejected their grafts (wk10, wk14, wk16). All dogs in groups 2 and 3 rejected their graft (median: wk 10 and 11, respectively). Peak chimerism and engraftment duration was shorter in the 1Gy groups (p<0.05) compared to group 1. Conclusion Neither postgrafting vaccination nor graft augmentation with MoDC were effective in supporting durable engraftment. Additional modifications are neccessary to improve potential strategies aimed at establishment of early tissue specific graft-versus-host reactions. PMID:19100524

  15. Progenitor Cells and Podocyte Regeneration

    Science.gov (United States)

    Shankland, Stuart J.; Pippin, Jeffrey W.; Duffield, Jeremy S.

    2014-01-01

    The very limited ability of adult podocytes to proliferate in vivo is clinically significant because: podocytes form a vascular barrier which is functionally critical to the nephron; podocyte hypoplasia is a characteristic of disease; and inadequate regeneration of podocytes is a major cause of persistent podocyte hypoplasia. Excessive podocyte loss or inadequate replacement leads to glomerulosclerosis in many progressive kidney diseases. Thus, restoration of podocyte cell density is almost certainly reliant on regeneration by podocyte progenitors. However such putative progenitors have remained elusive until recently. In this review we describe the developmental processes leading to podocyte and parietal epithelial cell (PEC) formation during glomerulogenesis. We compare evidence that in normal human kidneys PECs expressing ‘progenitor’ markers CD133 and CD24 can differentiate into podocytes in vitro and in vivo with evidence from animal models suggesting a more limited role of PEC-capacity to serve as podocyte progenitors in adults. We will highlight tantalizing new evidence that specialized vascular wall cells of afferent arterioles including those which produce renin in healthy kidney, provide a novel local progenitor source of new PECs and podocytes in response to podocyte hypoplasia in the adult, and draw comparisons with glomerulogenesis. PMID:25217270

  16. Human Blood-Vessel-Derived Stem Cells for Tissue Repair and Regeneration

    OpenAIRE

    Chien-Wen Chen; Mirko Corselli; Bruno Péault; Johnny Huard

    2012-01-01

    Multipotent stem/progenitor cells with similar developmental potentials have been independently identified from diverse human tissue/organ cultures. The increasing recognition of the vascular/perivascular origin of mesenchymal precursors suggested blood vessels being a systemic source of adult stem/progenitor cells. Our group and other laboratories recently isolated multiple stem/progenitor cell subsets from blood vessels of adult human tissues. Each of the three structural layers of blood ve...

  17. Trasplante de progenitores hemopoyéticos Transplant of hemopoietic progenitors

    Directory of Open Access Journals (Sweden)

    J. J. Rifón

    2006-08-01

    Full Text Available En la segunda mitad del siglo XX el trasplante de progenitores hemopoyéticos ha pasado de ser un tratamiento desesperado con una alta incidencia de complicaciones que implicaba una elevada mortalidad, a ser un tratamiento curativo para miles de pacientes con neoplasias hematológicas y otras enfermedades. Desde entonces se han ampliado los conocimientos sobre las células madre hemopoyéticas, la sangre periférica ha sustituido a la médula ósea como fuente de progenitores, la sangre de cordón se ha establecido como fuente viable de progenitores, la realización de trasplantes no emparentados es una realidad para muchos pacientes. La mejora en los regímenes de acondicionamiento y la introducción de los regímenes no mieloablativos han disminuido las recaídas. Las nuevas técnicas diagnósticas y los nuevos tratamientos antimicrobianos han disminuido las complicaciones infecciosas y su mortalidad. Se han desarrollado los conocimientos en determinación de enfermedad mínima residual y el efecto antitumoral de los linfocitos del donante lo que ha permitido ampliar las indicaciones. Además, los nuevos conocimientos en la inmunobiología del trasplante han mejorado por un lado las opciones de controlar una de las principales complicaciones como es la enfermedad injerto contra huésped, y por otro un mejor aprovechamiento del efecto inmunoterápico del trasplante.In the second half of the XX century, the transplant of hemopoietic progenitors ceased to be a desperate treatment with a high incidence of complications implying a high mortality, and became a curative treatment for thousands of patients with hematological neoplasias and other diseases. Since then understanding of the hemopoietic stem cells has increased, peripheral blood has replaced bone marrow as a source of progenitors, cord blood has been established as a viable source of progenitors and the realisation of unrelated transplants is a reality for many patients. The improvement of

  18. Dysregulation of Vascular Endothelial Progenitor Cells Lung-Homing in Subjects with COPD

    Directory of Open Access Journals (Sweden)

    Brittany M. Salter

    2016-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by fixed airflow limitation and progressive decline of lung function and punctuated by occasional exacerbations. The disease pathogenesis may involve activation of the bone marrow stimulating mobilization and lung-homing of progenitor cells. We investigated the hypothesis that lower circulating numbers of vascular endothelial progenitor cells (VEPCs are a consequence of increased lung-sequestration in COPD. Nonatopic, current or ex-smokers with diagnosed COPD and nonatopic, nonsmoking normal controls were enrolled. Blood and induced sputum extracted primitive hemopoietic progenitors (HPCs and VEPC were enumerated by flow cytometry. Migration and adhesive responses to fibronectin were assessed. In sputum, VEPC numbers were significantly greater in COPD compared to normal controls. In blood, VEPCs were significantly lower in COPD versus normal controls. There were no differences in HPC levels between the two groups in either compartment. Functionally, there was a greater migrational responsiveness of progenitors from COPD subjects to stromal cell-derived factor-1alpha (SDF-1α compared to normal controls. This was associated with greater numbers of CXCR4+ progenitors in sputum from COPD. Increased migrational responsiveness of progenitor cells may promote lung-homing of VEPC in COPD which may disrupt maintenance and repair of the airways and contribute to COPD disease pathogenesis.

  19. Longitudinal analysis of antibody response to immunization in paediatric survivors after allogeneic haematopoietic stem cell transplantation

    Science.gov (United States)

    Inaba, Hiroto; Hartford, Christine M.; Pei, Deqing; Posner, Meredith J.; Yang, Jie; Hayden, Randall T.; Srinivasan, Ashok; Triplett, Brandon M.; McCulllers, Jon A.; Pui, Ching-Hon; Leung, Wing

    2011-01-01

    Summary The long-term antibody responses to re-immunization in recipients of allogeneic haematopoietic stem cell transplantation (allo-HSCT) have not been well studied. We prospectively and longitudinally evaluated the antibody responses to 8 vaccine antigens (diphtheria, tetanus, pertussis, measles, mumps, rubella, hepatitis B, and poliovirus) and assessed the factors associated with negative titres in 210 allo-HSCT recipients at St. Jude Children’s Research Hospital. Antibody responses lasting for more than 5 years after immunization were observed in most patients for tetanus (95.7%), rubella (92.3%), poliovirus (97.9%), and, in diphtheria-tetanus-acellular pertussis (DTaP) recipients, diphtheria (100%). However, responses to pertussis (25.0%), measles (66.7%), mumps (61.5%), hepatitis B (72.9%), and diphtheria in tetanus-diphtheria (Td) recipients (48.6%) were less favourable, with either only transient antibody responses or persistently negative titres. Factors associated with vaccine failure were older age at immunization; lower CD3, CD4 or CD19 counts; higher IgM concentrations; positive recipient cytomegalovirus serology; negative titres before immunization; acute or chronic graft-versus-host disease; and radiation during preconditioning. These response patterns and clinical factors can be used to formulate re-immunization and monitoring strategies. Patients at risk for vaccine failure should have long-term follow-up; those with loss of antibody response or no seroconversion should receive booster immunizations. PMID:22017512

  20. Determine the difficulties of home care in children following haematopoietic stem cell transplantation.

    Science.gov (United States)

    Kılıcarslan Toruner, E; Altay, N; Kisecik, Z

    2016-07-01

    The aim of this study was to determine the difficulties regarding the home care of children following haematopoietic stem cell transplantation (HSCT). The sample of the study includes the families of 73 children in a bone marrow transplant unit between 2010 and 2013, Turkey. Data were collected using a form included descriptive information and questions about the difficulties and complications of home care. Families were telephoned and problems they had encountered were recorded. Mann-Whitney U-test and the logistic regression analysis were used. The average age of the children was 10.65 ± 5.03 years, the average age was 8.89 ± 4.9 when HSCT was performed, and the average year after HSCT was 1.79 ± 0.74. 41.1% of the children underwent transplantation with diagnoses of anaemia. Primary physical problems that were found after discharge from the hospital were fever (43.8%), decreased appetite (37%), rash (34.2%) and pain (26%). Socially, 43.8% of families reported that their children had difficulties with school. Primary difficulties regarding care and follow-up were reported as skin care (34.2%) and catheter care (33.3%). In the post-transplantation period, it is important to provide information about potential problems and care to patients and families in order to increase the quality of life.

  1. Haematopoietic Stem Cell Transplantation for Refractory Langerhans Cell Histiocytosis: Outcome by Intensity of Conditioning

    Science.gov (United States)

    Veys, Paul A.; Nanduri, Vasanta; Baker, K. Scott; He, Wensheng; Bandini, Giuseppe; Biondi, Andrea; Dalissier, Arnaud; Davis, Jeffrey H.; Eames, Gretchen M.; Egeler, R. Maarten; Filipovich, Alexandra H.; Fischer, Alain; Jürgens, Herbert; Krance, Robert; Lanino, Edoardo; Leung, Wing H.; Matthes, Susanne; Michel, Gérard; Orchard, Paul J.; Pieczonka, Anna; Ringdén, Olle; Schlegel, Paul G.; Sirvent, Anne; Vettenranta, Kim; Eapen, Mary

    2015-01-01

    Summary Patients with Langerhans cell histiocytosis (LCH) refractory to conventional chemotherapy have a poor outcome. There are currently two promising treatment strategies for high-risk patients: the first involves the combination of 2-chlorodeoxyadenosine and cytarbine; the other approach is allogeneic haematopoietic stem cell transplantation (HSCT). Here we evaluated 87 patients with high-risk LCH who were transplanted between 1990–2013. Prior to the year 2000, most patients underwent HSCT following myeloablative conditioning (MAC): only 5 of 20 patients (25%) survived with a high rate (55%) of transplant-related mortality (TRM). After the year 2000 an increasing number of patients underwent HSCT with reduced intensity conditioning (RIC): 49/67 (73%) patients survived, however, the improved survival was not overtly achieved by the introduction of RIC regimens with similar 3-year probability of survival after MAC (77%) and RIC transplantation (71%). There was no significant difference in TRM by conditioning regimen intensity but relapse rates were higher after RIC compared to MAC regimens (28% vs. 8%, p=0.02), although most patients relapsing after RIC transplantation could be salvaged with further chemotherapy. HSCT may be a curative approach in 3 out of 4 patients with high risk LCH refractory to chemotherapy: the optimal choice of HSCT conditioning remains uncertain. PMID:25817915

  2. Development and evaluation of a specifically designed website for haematopoietic stem cell transplant patients in Leeds.

    Science.gov (United States)

    Horne, B; Newsham, A; Velikova, G; Liebersbach, S; Gilleece, M; Wright, P

    2016-05-01

    The purpose of this project was to develop and evaluate a specifically designed website (ALLograft INformation EXchange - ALLINEX) for adult allogeneic haematopoietic stem cell transplant (allo-HSCT) patients in Leeds. Specifications included information on the transplant journey and supportive care services, discussion forum and patient-clinical team electronic messaging service. The method followed a participatory action research approach in a five-phase project involving stakeholders. Phase 1 involved information gathering; Phase 2 development of content; Phase 3 building of website and usability testing; Phase 4 preliminary evaluation; and Phase 5 clinical implementation. Results concluded that Phase 1 patients were unaware of all services and reported unmet needs; gaps in support services were identified from a service evaluation; Phase 2 content was collected from experts, collated and synthesised; Phase 3 patient and staff feedback was positive and constructive resulting in more than 50 changes; Phase 4 ALLINEX evaluation demonstrated acceptable usability with good layout, content and aesthetics reported; Phase 5, over 15 weeks, ALLINEX had 6630 page hits, 9 new forum topics posted and received 3 clinical messages. The clinical team embraced responsibility for reviewing and monitoring ALLINEX. Financial and indemnity cover was secured for 3 years. ALLINEX, adopted locally, is sustainable and has functionality to roll-out to other UK allo-HSCT centres. PMID:26215187

  3. Immune reconstitution after haematopoietic transplantation with two different doses of pre-graft antithymocyte globulin.

    Science.gov (United States)

    Duval, M; Pédron, B; Rohrlich, P; Legrand, F; Faye, A; Lescoeur, B; Bensaid, P; Larchee, R; Sterkers, G; Vilmer, E

    2002-10-01

    Antithymocyte globulin is widely used before haematopoietic transplantation with HLA-matched unrelated donors or mismatched relatives to prevent rejection and graft-versus-host disease (GVHD). However, optimal dosage is still under debate. Thirty-one consecutive children, mainly with haematological malignancies, were transplanted in a single institution with such donors, selected by HLA-A -B compatibility by serology and DRB1* by DNA typing. Antithymocyte globulin (Thymoglobuline; Sangstat) was infused at days -3, -2, -1. Total dosage varied: 16 patients received a median of 7.5 mg/kg (2.5 to 10.5: low-dose group), and 15 a median of 15.5 mg/kg (14.4 to 19.4: high-dose group). Post-transplant GVHD prophylaxis consisted of cyclosporine, short-course methotrexate and steroids. CD3(+), CD4(+) and CD19(+) cell reconstitution was slower in the high-dose group. Median time to reach 100 CD4(+) cells was 8 months vs 4 months (P = 0.03). Median time to normal CD19(+) cells was 16 months vs 8 months (P = 0.01). CD16(+)CD56(+) and CD8(+) cell reconstitution was similar. Nine patients in the high-dose group and two in the low-dose group experienced life-threatening opportunistic infections (P = 0.009). Although obtained from a limited number of patients, our data suggest that a higher pre-graft dose of antithymocyte globulin may negatively influence immune reconstitution.

  4. Diffuse gastrointestinal bleeding and BK polyomavirus replication in a pediatric allogeneic haematopoietic stem cell transplant patient.

    Science.gov (United States)

    Koskenvuo, M; Lautenschlager, I; Kardas, P; Auvinen, E; Mannonen, L; Huttunen, P; Taskinen, M; Vettenranta, K; Hirsch, H H

    2015-01-01

    Patients undergoing haematopoietic stem cell transplantation (HSCT) are at high risk of severe gastrointestinal bleeding caused by infections, graft versus host disease, and disturbances in haemostasis. BK polyomavirus (BKPyV) is known to cause hemorrhagic cystitis, but there is also evidence of BKV shedding in stool and its association with gastrointestinal disease. We report putative association of BKPyV replication with high plasma viral loads in a pediatric HSCT patient developing hemorrhagic cystitis and severe gastrointestinal bleeding necessitating intensive care. The observation was based on chart review and analysis of BKPyV DNA loads in plasma and urine as well as retrospective BKPyV-specific IgM and IgG measurements in weekly samples until three months post-transplant. The gastrointestinal bleeding was observed after a >100-fold increase in the plasma BKPyV loads and the start of hemorrhagic cystitis. The BKPyV-specific antibody response indicated past infection prior to transplantation, but increasing IgG titers were seen following BKPyV replication. The gastrointestinal biopsies were taken at a late stage of the episode and were no longer informative of BK polyomavirus involvement. In conclusion, gastrointestinal complications with bleeding are a significant problem after allogeneic HSCT to which viral infections including BKPyV may contribute. PMID:25542476

  5. Gene expression profiling of human erythroid progenitors by micro-serial analysis of gene expression.

    Science.gov (United States)

    Fujishima, Naohito; Hirokawa, Makoto; Aiba, Namiko; Ichikawa, Yoshikazu; Fujishima, Masumi; Komatsuda, Atsushi; Suzuki, Yoshiko; Kawabata, Yoshinari; Miura, Ikuo; Sawada, Ken-ichi

    2004-10-01

    We compared the expression profiles of highly purified human CD34+ cells and erythroid progenitor cells by micro-serial analysis of gene expression (microSAGE). Human CD34+ cells were purified from granulocyte colony-stimulating factor-mobilized blood stem cells, and erythroid progenitors were obtained by cultivating these cells in the presence of stem cell factor, interleukin 3, and erythropoietin. Our 10,202 SAGE tags allowed us to identify 1354 different transcripts appearing more than once. Erythroid progenitor cells showed increased expression of LRBA, EEF1A1, HSPCA, PILRB, RANBP1, NACA, and SMURF. Overexpression of HSPCA was confirmed by real-time polymerase chain reaction analysis. MicroSAGE revealed an unexpected preferential expression of several genes in erythroid progenitor cells in addition to the known functional genes, including hemoglobins. Our results provide reference data for future studies of gene expression in various hematopoietic disorders, including myelodysplastic syndrome and leukemia.

  6. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins.

    Science.gov (United States)

    Fukusumi, Hayato; Shofuda, Tomoko; Bamba, Yohei; Yamamoto, Atsuyo; Kanematsu, Daisuke; Handa, Yukako; Okita, Keisuke; Nakamura, Masaya; Yamanaka, Shinya; Okano, Hideyuki; Kanemura, Yonehiro

    2016-01-01

    Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes.

  7. The poster as modernist progenitor

    Directory of Open Access Journals (Sweden)

    Katherine Hauser

    2015-12-01

    Full Text Available Ruth E. Iskin’s The Poster: Art, Advertising. Design, and Collecting, 1860s-1900s positions the late-nineteenth-century advertising poster as the progenitor of valued modernist practices typically attached solely to photography and film. Modernist biases separating high art from mass culture account for scholars ignoring posters, however the poster ushered in an innovative reductive graphic style as well as pioneered the notion of multiple originals.

  8. 人巨细胞病毒感染致造血祖细胞增殖抑制与更昔洛韦的影响%Inhibitory effect of ganciclovir on proliferation of cord blood hematopoietic progenitor cells after infection of human cytomegalovirus in vitro

    Institute of Scientific and Technical Information of China (English)

    刘文君; 刘斌; 郭渠莲; 付晓冬; 邓正华

    2008-01-01

    BACKGROUND: Clinically, in patients undergoing hematopoietic stem cell transplantation (HSCT), human cytomegalovirus (HCMV) can be associated with delayed platelet engraftment, phenotypically abnormal peripheral blood leukocytes, and graft rejection, possibly through a direct viral effect on hematopoietic progenitor cells after HCMV infection. OBJECTIVE: To investigate the inhibitory effect of ganciclovir (GCV) on proliferation of colony forming unit (CFU) granulocyte-macrophage (CFU-GM), CFU-erythroid (CFU-E), CFU T-lymphocyte (CFU-TL), CFU-multipotential (CFU-Mix) and CFU-megakaryocyte (CFU-Mk) progenitor cells of cord blood (CB) and the protective effects on them. DESIGN: Contrast observational study.SETTING: Department of Molecular Biology, Affiliated Hospital of Luzhou Medical College.PARTICIPANTS: A total of 20 cord blood (CB) samples (with 10 mL for each sample) from fetal umbilical vein of normal term spontaneous delivery neonates were provided by the Department of Gynaecology and Obstetrics, Affiliated Hospital of Luzhou Medical College. All the patients were informed and agreed with the experiment.METHODS: The experiment was carried out in the Department of Molecular Biology, Affiliated Hospital of Luzhou Medical College from June 2004 to December 2006. Colony forming unit-assay was applied to observe the suppression effect of HCMV-AD169 strain on CFU-GM, CFU-E, CFU-TL, CFU-Mix and CFU-Mk of CB with the presence of GCV. The techniques of polymerase chain reaction (PCR) and fluorescence quantification PCR were used to demonstrate the existence of HCMV-AD169 DNA in the colony cells of cultured CFU-GM, CFU-E, CFU-TL, CFU-Mix and CFU-Mk. Normal progenitor cells culture system was regarded as blank control group; normal progenitor cells culture system with inactivated HCMV fluid as inactivated (IV) control group.MAIN OUTCOME MEASURES: ① The number and maintaining duration of colonies of cultured progenitor cells were counted by using a light inverted phase

  9. Endothelial progenitor cells with Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    KONG Xiao-dong; ZHANG Yun; LIU Li; SUN Ning; ZHANG Ming-yi; ZHANG Jian-ning

    2011-01-01

    Background Endothelial dysfunction is thought to be critical events in the pathogenesis of Alzheimer's disease (AD).Endothelial progenitor cells (EPCs) have provided insight into maintaining and repairing endothelial function. To study the relation between EPCs and AD, we explored the number of circulating EPCs in patients with AD.Methods A total of 104 patients were recruited from both the outpatients and inpatients of the geriatric neurology department at General Hospital, rianjin Medical University. Consecutive patients with newly diagnosed AD (n=30),patients with vascular dementia (VaD, n=34), and healthy elderly control subjects with normal cognition (n=40) were enrolled after matching for age, gender, body mass index, medical history, current medication and Mini Mental State Examination. Middle cerebral artery flow velocity was examined with transcranial Doppler. Endothelial function was evaluated according to the level of EPCs, and peripheral blood EPCs was counted by flow cytometry.Results There were no significant statistical differences of clinical data in AD, VaD and control groups (P >0.05). The patients with AD showed decreased CD34-positive (CD34+) or CD133-positive (CD133+) levels compared to the control subjects, but there were no significant statistical differences in patients with AD. The patients with AD had significantly lower CD34+CD133+ EPCs(CD34 and CD133 double positive endothelial progenitor cells) than the control subjects (P <0.05). In the patients with AD, a lower CD34+CD133+ EPCs count was independently associated with a lower Mini-Mental State Examination score (r=0.514, P=0.004). Patients with VaD also showed a significant decrease in CD34+CD133+ EPCs levels, but this was not evidently associated with the Mini-Mental State Examination score. The changes of middle cerebral artery flow velocity were similar between AD and VaD. Middle cerebral artery flow velocity was decreased in the AD and VaD groups and significantly lower than

  10. Human haematopoietic stem cells express Oct4 pseudogenes and lack the ability to initiate Oct4 promoter-driven gene expression

    Directory of Open Access Journals (Sweden)

    Strain Alastair J

    2010-03-01

    Full Text Available Abstract The transcription factor Oct4 is well defined as a key regulator of embryonic stem (ES cell pluripotency. In recent years, the role of Oct4 has purportedly extended to the self renewal and maintenance of multipotency in adult stem cell (ASC populations. This profile has arisen mainly from reports utilising reverse transcription-polymerase chain reaction (RT-PCR based methodologies and has since come under scrutiny following the discovery that many developmental genes have multiple pseudogenes associated with them. Six known pseudogenes exist for Oct4, all of which exhibit very high sequence homology (three >97%, and for this reason the generation of artefacts may have contributed to false identification of Oct4 in somatic cell populations. While ASC lack a molecular blueprint of transcription factors proposed to be involved with 'stemness' as described for ES cells, it is not unreasonable to assume that similar gene patterns may exist. The focus of this work was to corroborate reports that Oct4 is involved in the regulation of ASC self-renewal and differentiation, using a combination of methodologies to rule out pseudogene interference. Haematopoietic stem cells (HSC derived from human umbilical cord blood (UCB and various differentiated cell lines underwent RT-PCR, product sequencing and transfection studies using an Oct4 promoter-driven reporter. In summary, only the positive control expressed Oct4, with all other cell types expressing a variety of Oct4 pseudogenes. Somatic cells were incapable of utilising an exogenous Oct4 promoter construct, leading to the conclusion that Oct4 does not appear involved in the multipotency of human HSC from UCB.

  11. Haematopoietic stem cell transplantation in Nigerian sickle cell anaemia children patients

    Directory of Open Access Journals (Sweden)

    Antonella Isgro

    2015-01-01

    Full Text Available Background: Sickle cell anaemia (SCA remains associated with high risks of morbidity and early death. Children with SCA are at high risk for ischaemic stroke and transient ischaemic attacks, secondary to intracranial arteriopathy involving carotid and cerebral arteries. Allogeneic haematopoietic stem cell transplantation (HSCT is the only curative treatment for SCA. We report our experience with transplantation in a group of patients with the Black African variant of SCA. Patients and Methods: This study included 31 consecutive SCA patients who underwent bone marrow transplantation from human leukocyte antigen (HLA-identical sibling donors between 2010 and 2014 following a myeloablative-conditioning regimen. Results: The median patient age was 10 years (range 2-17 years. Before transplantation, 14 patients had recurrent, painful, vaso-occlusive crisis; ten patients had recurrent painful crisis in association with acute chest syndrome; three patients experienced ischaemic stroke and recurrent vaso-occlusive crisis; two patients experienced ischaemic stroke; one patient exhibited leukocytosis; and one patient exhibited priapism. Of the 31 patients, 28 survived without sickle cell disease, with Lansky/Karnofsky scores of 100. All surviving patients remained free of any SCA-related events after transplantation. Conclusion: The protocols used for the preparation to the transplant in thalassaemia are very effective also in the other severe haemoglobinopathy as in the sickle cell anaemia with 90% disease free survival. Today, if a SCA patient has a HLA identical family member, the cellular gene therapy through the transplantation of the allogeneic haemopoietic cell should be performed. Tomorrow, hopefully, the autologous genetically corrected stem cell will break down the wall of the immunological incompatibility.

  12. [Nosocomial infection in patients receiving a solid organ transplant or haematopoietic stem cell transplant].

    Science.gov (United States)

    Moreno Camacho, Asunción; Ruiz Camps, Isabel

    2014-01-01

    Bacterial infections are the most common infections in solid organ transplant recipients. These infections occur mainly in the first month after transplantation and are hospital-acquired. Nosocomial infections cause significant morbidity and are the most common cause of mortality in this early period of transplantation. These infections are caused by multi-drug resistant (MDR) microorganisms, mainly Gram-negative enterobacteria, non-fermentative Gram-negative bacilli, enterococci, and staphylococci. The patients at risk of developing nosocomial bacterial infections are those previously colonized with MDR bacteria while on the transplant waiting list. Intravascular catheters, the urinary tract, the lungs, and surgical wounds are the most frequent sources of infection. Preventive measures are the same as those applied in non-immunocompromised, hospitalized patients except in patients at high risk for developing fungal infection. These patients need antifungal therapy during their hospitalization, and for preventing some bacterial infections in the early transplant period, patients need vaccinations on the waiting list according to the current recommendations. Although morbidity and mortality related to infectious diseases have decreased during the last few years in haematopoietic stem cell transplant recipients, they are still one of the most important complications in this population. Furthermore, as occurs in the general population, the incidence of nosocomial infections has increased during the different phases of transplantation. It is difficult to establish general preventive measures in these patients, as there are many risk factors conditioning these infections. Firstly, they undergo multiple antibiotic treatments and interventions; secondly, there is a wide variability in the degree of neutropenia and immunosuppression among patients, and finally they combine hospital and home stay during the transplant process. However, some simple measures could be

  13. NK cells and other innate lymphoid cells in haematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Paola eVacca

    2016-05-01

    Full Text Available Natural Killer (NK cells play a major role in the T-cell depleted haploidentical haematopoietic stem cell transplantation (haplo-HSCT to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILC. At variance with NK cells, the other ILC populations (ILC1/2/3 are non-cytolytic, while they secrete different patterns of cytokines. ILC provide host defences against viruses, bacteria and parasites, drive lymphoid organogenesis, and contribute to tissue remodelling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defences that are reconstituted more rapidly than the adaptive ones. In this context, ILC may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodelling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILC. Of note, CD34+ cells isolated from different sources of HSC, may differentiate in vitro towards various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g. IL-1β may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.

  14. Urological management (medical and surgical) of BK-virus associated haemorrhagic cystitis in children following haematopoietic stem cell transplantation

    OpenAIRE

    Nikhil Vasdev; Angela Davidson; Christian Harkensee; Mary Slatter; Andrew Gennery; Ian Willetts; Andrew Thorpe

    2013-01-01

    Aim: Haemorrhagic cystitis (HC) is uncommon and in its severe form potentially life threatening complication of Haematopoietic stem cell transplantation (HSCT) in children. We present our single centre experience in the urological management of this clinically challenging condition. Patients and Methods: Fourteen patients were diagnosed with BK-Virus HC in our centre. The mean age at diagnosis was 8.8 years (range, 3.2-18.4 years). The mean number of days post-BMT until onset of HC was 20.8 (...

  15. Differential Stem and Progenitor Cell Trafficking by Prostaglandin E2

    Science.gov (United States)

    Hoggatt, Jonathan; Mohammad, Khalid S.; Singh, Pratibha; Hoggatt, Amber F.; Chitteti, Brahmananda Reddy; Speth, Jennifer M.; Hu, Peirong; Poteat, Bradley A.; Stilger, Kayla N.; Ferraro, Francesca; Silberstein, Lev; Wong, Frankie K.; Farag, Sherif S.; Czader, Magdalena; Milne, Ginger L.; Breyer, Richard M.; Serezani, Carlos H.; Scadden, David T.; Guise, Theresa; Srour, Edward F.; Pelus, Louis M.

    2013-01-01

    SUMMARY To maintain lifelong production of blood cells, hematopoietic stem cells (HSC) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSC (LT-HSC) reside in several, perhaps overlapping, niches that produce regulatory molecules/signals necessary for homeostasis and increased output following stress/injury 1–5. Despite significant advances in specific cellular or molecular mechanisms governing HSC/niche interactions, little is understood about regulatory function within the intact mammalian hematopoietic niche. Recently, we and others described a positive regulatory role for Prostaglandin E2 (PGE2) on HSC function ex vivo 6,7. While exploring the role of endogenous PGE2 we unexpectedly observed hematopoietic egress after nonsteroidal anti-inflammatory drug (NSAID) treatment. Surprisingly, this was independent of the SDF-1/CXCR4 axis. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin (OPN). Hematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in higher species. PGE2 receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced EP4 receptor signaling. These results not only uncover unique regulatory roles for EP4 signaling in HSC retention in the niche but also define a rapidly translatable strategy to therapeutically enhance transplantation. PMID:23485965

  16. Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Caterina Oriana Aragona

    2016-01-01

    Full Text Available Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs in cardiovascular disease, through a systematic review of quantitative studies. Data Sources. MEDLINE was searched using keywords related to “endothelial progenitor cells” and “endothelium” and, for the different categories, respectively, “smoking”; “blood pressure”; “diabetes mellitus” or “insulin resistance”; “dyslipidemia”; “aging” or “elderly”; “angina pectoris” or “myocardial infarction”; “stroke” or “cerebrovascular disease”; “homocysteine”; “C-reactive protein”; “vitamin D”. Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included. Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers. Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: Prospero CRD42015023717.

  17. Experiment list: SRX1338948 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=Progenitor cells from which all blood cells derive. 38012300,94.7,8.9,314 GSM1909032: Sensitive line... ChIP input; Mus musculus; ChIP-Seq source_name=Sensitive line || tissue=haematopoietic progenitors || condition=Sensitive

  18. Experiment list: SRX1293141 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Progenitor cells from which all blood cells derive. 18837531,97.0,19.2,4704 GSM1897160: Sensitive line BRD4 ...ChIP; Mus musculus; ChIP-Seq source_name=Sensitive line || tissue=haematopoietic progenitors || condition=Sensitive

  19. Experiment list: SRX1293143 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available n=Progenitor cells from which all blood cells derive. 21855080,81.4,74.1,125 GSM1897162: Sensitive line Bcat... ChIP; Mus musculus; ChIP-Seq source_name=Sensitive line || tissue=haematopoietic progenitors || condition=Sensitive

  20. Effect of matrix composition on differentiation of nestin-positive neural progenitors from circulation into neurons

    Science.gov (United States)

    Jose, Anumol; Krishnan, Lissy K.

    2010-06-01

    The human peripheral blood mononuclear cell has a mixture of progenitor cells with potential to differentiate into a wide range of lineages. The ability of hematopoietic tissue-derived adult stem cells to differentiate into neural progenitor cells offers an alternative to embryonic stem cells as a viable source for cell transplantation therapies to cure neurodegenerative diseases. This approach could lead to the use of autologous progenitors from blood circulation; however, due to the limited numbers available, in vitro cell expansion may be indispensable. In addition, for successful transplantation there is the requirement of a delivery matrix on which cells can survive and differentiate. In this context we carried out this study to identify a suitable biodegradable matrix on which progenitor cells can home, multiply and differentiate. We designed different compositions of the biomimetic matrix containing fibrin, fibronectin, gelatin, growth factors, laminin and hyaluronic acid. The attached cells expressed proliferation markers in initial periods of culture and between days 6 and 9 in culture they differentiated into neurons and/or astrocytes. The differentiation of progenitors into neurons and asterocyte on the composed matrix was established by morphological and immunochemical analysis. Flow cytometric analysis of cells in culture was employed to track development of neurons which expressed an early marker β-tubulin3 and a terminal marker microtubule-associated protein-2 at a later culture period. In vitro experiments indicate that a highly specific niche consisting of various components of the extracellular matrix, including hyaluronic acid, promote cell homing, survival and differentiation.

  1. 血管内皮生长因子和雌二醇促进血管内皮祖细胞分化生成血管的对比研究%Comparative study of vascular endothelial growth factor and estradiol in promoting endothelial progenitor cells differentiation and generation blood vessels

    Institute of Scientific and Technical Information of China (English)

    董勇; 李文志; 辛毅; 孙智

    2013-01-01

    Objective To compare the ability of vascular endothelial growth factor (VEGF) and estradiol in promoting endothelial progenitor cells differentiation and generation blood vessels under common doses. Methods To isolate and culture human peripheral blood EPCs first, then to mixe with the matrigel and transplante to the lower abdomens of nine nude mice.to divide the nine nude mice into three groups according to a random grouping, to inject VEGF.estradiol and saline at a regular time,to observe and record the growing status of vascular tissue regularly.to draw the vascular tissue after six weeks, to observe the organizational structure by HE staining, then contrast with the groups. Results The vascular tissue volume groups injected of drugs have significant difference with the groups injected of saline.they have bigger volume to contrast the groups injected of saline, but he vascular tissue volume between the groups injected of drugs is no significant difference. By drawning HE staining, the vascular tissues have proliferational mussy blood vessels.The vascular density of the groups injected of drugs is significantly greater than the groups injected of saline, but he vascular density between the groups injected of drugs is small. Conclusion VEGF and estradiol can promote EPCs differentiation and generation blood vessels.their respective promoting EPCs differentiation and generation blood vessels potency is no significant difference under common doses.%目的:对比研究常规剂量下血管内皮生长因子(VEGF)和雌二醇对血管内皮祖细胞(EPCs)分化生成血管的促进作用.方法:分离培养人外周血EPCs,与基质胶混匀后注射到9只裸鼠双侧下腹部,另设2只注射等体积培养液与基质胶的混合液.将9只注射细胞的裸鼠随机分为3组,每组分别定期局部注射VEGF、雌二醇,生理盐水,定期观察记录血管组织块的生长状况.移植6周后取材,测量计算血管组织块的体积、HE染色观察血管

  2. Enzyme replacement therapy prior to haematopoietic stem cell transplantation in Mucopolysaccharidosis Type I: 10year combined experience of 2 centres.

    Science.gov (United States)

    Ghosh, Arunabha; Miller, Weston; Orchard, Paul J; Jones, Simon A; Mercer, Jean; Church, Heather J; Tylee, Karen; Lund, Troy; Bigger, Brian W; Tolar, Jakub; Wynn, Robert F

    2016-03-01

    Haematopoietic stem cell transplantation is the treatment of choice for the severe form of Mucopolysaccharidosis Type I, or Hurler syndrome. In many centres standard practice is to deliver enzyme replacement therapy alongside haematopoietic stem cell transplantation to improve the condition of the patient prior to transplant. We report the combined 10year experience of this approach in two paediatric metabolic and transplant centres. Of 81 patients who underwent a first transplant procedure for Hurler, 88% (71/81) survived and 81% (66/81) were alive and engrafted at a median follow-up of 46months (range 3-124months). The incidence of grade II-IV acute and any chronic graft versus host disease was 17% and 11% respectively. Urinary glycosaminoglycans were significantly reduced after a period of enzyme replacement therapy, and further reductions were seen at 13-24months and 25+months after transplantation. In several individuals with decreased cardiac contractility, an improvement of their condition during enzyme replacement therapy enabled them to undergo transplantation, with one individual receiving full intensity conditioning. PMID:26832957

  3. Pharmacokinetics, Pharmacodynamics and Pharmacogenomics of Immunosuppressants in Allogeneic Haematopoietic Cell Transplantation: Part I.

    Science.gov (United States)

    McCune, Jeannine S; Bemer, Meagan J

    2016-05-01

    Although immunosuppressive treatments and target concentration intervention (TCI) have significantly contributed to the success of allogeneic haematopoietic cell transplantation (alloHCT), there is currently no consensus on the best immunosuppressive strategies. Compared with solid organ transplantation, alloHCT is unique because of the potential for bidirectional reactions (i.e. host-versus-graft and graft-versus-host). Postgraft immunosuppression typically includes a calcineurin inhibitor (cyclosporine or tacrolimus) and a short course of methotrexate after high-dose myeloablative conditioning, or a calcineurin inhibitor and mycophenolate mofetil after reduced-intensity conditioning. There are evolving roles for the antithymyocyte globulins (ATGs) and sirolimus as postgraft immunosuppression. A review of the pharmacokinetics and TCI of the main postgraft immunosuppressants is presented in this two-part review. All immunosuppressants are characterized by large intra- and interindividual pharmacokinetic variability and by narrow therapeutic indices. It is essential to understand immunosuppressants' pharmacokinetic properties and how to use them for individualized treatment incorporating TCI to improve outcomes. TCI, which is mandatory for the calcineurin inhibitors and sirolimus, has become an integral part of postgraft immunosuppression. TCI is usually based on trough concentration monitoring, but other approaches include measurement of the area under the concentration-time curve (AUC) over the dosing interval or limited sampling schedules with maximum a posteriori Bayesian personalization approaches. Interpretation of pharmacodynamic results is hindered by the prevalence of studies enrolling only a small number of patients, variability in the allogeneic graft source and variability in postgraft immunosuppression. Given the curative potential of alloHCT, the pharmacodynamics of these immunosuppressants deserves to be explored in depth. Development of

  4. Effects of Angiotensin Ⅱ on Vascular Endothelial Growth Factor Expression in Early Endothelial Progenitor Cells from Human Peripheral Blood%血管紧张素Ⅱ对外周血早期内皮祖细胞血管内皮生长因子表达的影响

    Institute of Scientific and Technical Information of China (English)

    孙文文; 任国庆; 汪奕斌; 张浩

    2011-01-01

    Aim To investigate the effect of angiotensin Ⅱ on vascular endothelial growth factor expression of early endothelial progenitor cells. Methods Total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. After 7 days of culture, several groups of attached cells were incubated with angiotensin Ⅱ (to make a series of concentrations: 10-3 mol/L, 10 -5 mol/L, 10-7 mol/L vehicle control for 24 h), angiotensin Ⅱ + valsartan, angiotensin Ⅱ + PD123319. The cells were observed under inverted microscope, and characterized as adherent cells double positive for DiL DL-uptake and lectin binding by direct fluorescent staining under a laser scanning confocal microscope. The early endothelial progenitor cells were further documented by demonstrating the expression of cell markers with flow cytometry. Enzyme-linked immunospecific assay (ELISA) were used to assess vascular endothelial growth factor expression. Results Our data indicated that angiotensin Ⅱ can significantly increase the vascular endothelial growth factor expression, with a maximum at 10-3 mol/L after 24 hours (P <0. 05); These effects can be attenuated by pre-treatment with valsartan but not PD123319.Conclusion It is suggested that angiotensin Ⅱ induces vascular endothelial growth factor protein secretion via the angiotensin Ⅱ receptor-1 but not angiotensin Ⅱ receptor-2.%目的 观察血管紧张素Ⅱ对外周血早期内皮祖细胞血管内皮生长因子表达的影响.方法 密度梯度离心法获取外周血单个核细胞,培养7天,收集贴壁细胞,随机分对照组、血管紧张素Ⅱ各浓度 (10-3 mol/L、10-5 mol/L、10-7 mol/L) 组、血管紧张素Ⅱ+缬沙坦组、血管紧张素Ⅱ+ PD123319组.多波长激光共聚焦显微镜鉴定FITC标记荆豆凝集素Ⅰ和 DiI标记的乙酰化低密度脂蛋白双染色阳性为早期内皮祖细胞,流式细胞仪

  5. 金黄色葡萄球菌超抗原样蛋白-5抑制人脐血源性内皮祖细胞黏附功能及其机制研究%Staphylococcal superantigen-like protein-5 inhibits adhesion of human umbilical cord blood-derived endothelial progenitor cells to P-selectin-coated surface

    Institute of Scientific and Technical Information of China (English)

    梁华; 曲小龙; 胡厚源; 宋治远; 程彦; 张静

    2011-01-01

    目的 研究金黄色葡萄球菌超抗原样蛋白-5 (staphylococcal superantigen-like protein-5,SSL5)与人脐血源性内皮祖细胞(endothelial progenitor cells,EPCs)表面P-选择素糖蛋白配体-1 (P-selectin glycoprotein ligand-1,PSGL-1) 的结合情况,及其对内皮祖细胞黏附功能的影响.方法 从金黄色葡萄球菌 NCTC 8325菌株的基因组中,扩增ssl5基因,并进行重组SSL5蛋白表达载体的构建.采用密度梯度离心法分离得到脐血中的单个核细胞并进行体外培养,对贴壁细胞在激光共聚焦显微镜下观察其摄取乙酰化低密度脂蛋白(DiI-acLDL)和结合荆豆凝集素(FITC-UEA-1)的情况.以流式细胞仪分析SSL5与EPCs表面PSGL-1的结合情况;以calcein-AM负载EPCs后,定量分析SSL5对EPCs在P-选择素包被表面黏附的抑制作用.结果 DiI-acLDL/ FITC-UEA-1双染阳性的细胞为EPCs.PSGL-1在EPCs表面有较丰富的表达,阳性细胞率为76.6%.SSL5与EPCs的结合随着SSL5浓度的增加而显著升高;并且,SSL5可竞争性抑制抗PSGL-1单克隆抗体(KPL-1)与EPCs的结合.SSL5可显著抑制EPCs在P-选择素表面的黏附,终浓度为30 mg/L的SSL5对EPCs在P-选择素表面黏附的抑制率已接近10 mg/L的KPL-1的效应,两者与空白对照组比较,差异有统计学意义(P<0.01).结论 SSL5可与EPCs表面的PSGL-1结合,而抑制EPCs在P-选择素表面的黏附,提示SSL5可能通过抑制EPCs与损伤内皮或激活的血小板之间的黏附,进而抑制EPCs对损伤内皮的修复作用.%Objective To investigate the binding of staphylococcal superantigen-like protein-5 (SSL5) to P-selectin glycoprotein ligand-1 (PSGL-1) on human umbilical cord blood-derived endothelial progenitor cells (EPCs) and the inhibitive effect of SSL5 on the adhesion of EPCs to P-selectin-coated surface.Methods SSL5 gene was amplified from the genome of Staphylococcus aureus NCTC 8325 and cloned into a vector for expressing recombinant SSL5 protein. Mononuclear cells were

  6. The progenitors of stripped-envelope supernovae

    Science.gov (United States)

    Elias-Rosa, N.

    2013-05-01

    The type Ib/c SNe are those explosions which come from massive star populations, but lack hydrogen and helium. These have been proposed to originate in the explosions of massive Wolf-Rayet stars, and we should easily be able to detect the very luminous, young progenitors if they exist. However, there has not been any detection of progenitors so far. I present the study of two extinguished Type Ic SNe 2003jg and 2004cc. In both cases there is no clear evidence of a direct detection of their progenitors in deep pre-explosion images. Upper limits derived by inserting artificial stars of known brightness at random positions around the progenitor positions (M_v>-8.8 and M_v>-9 magnitudes for the progenitors of SN 2003jg and SN 2004cc, respectively) are brighter than those expected for a massive WC (Wolf-Rayet, carbon-rich) or WO (Wolf-Rayet, oxygen-rich) (e.g., approximately between -3 and -6 in the LMC). Therefore, this is perhaps further evidence that the most massive stars may give rise to black-holes forming SNe, or it is an undetected, compact massive star hidden by a thick dust lane. However the extinction toward these SNe is currently one of the largest known. Even if these results do not directly reveal the nature of the type Ic SN progenitors, they can help to characterize the dusty environment which surrounded the progenitor of the stripped-envelope CC-SNe.

  7. 阻塞性睡眠呼吸暂停患者外周血内皮祖细胞及促血管生成因子水平研究%T Endothelial progenitor cells (EPCs) and promote angiogenesis factor levels in peripheral blood in patients with obstructive sleep apnea

    Institute of Scientific and Technical Information of China (English)

    薛艳超; 孙蓓; 王新; 冯靖; 曹洁

    2016-01-01

    Objective To explore the repair possibilities of endothelial progenitor cells (EPCs)in peripheral blood in patients with different extents of obstructive sleep apnea (OSA) through measuring the levels of pro-angiogenic factors and different subgroups EPCs in peripheral blood in patients with OSA. Methods Ninety adult patients with OSA, 30 healthy controls with matched age and gender were enrolled for this study. The subjects performed Polysomnography, were divided in-to four group based on Apnea Hypopnea Index (AHI). The serum levels of HIF-1α, SDF-1αand VEGF were assessed by ELISA. Mononuclear cells were isolated from peripheral blood with density gradient centrifugation, and flow cytometry was used to detect levels of CD133+KDR+EPC, CD133+CD34+EPC, CD34+KDR+EPC and ALDHloCD34+KDR+EPC based on AL-DH activity, and CD133, CD34, PE-KDR related cell surface markers. Results The levels of CD133+KDR+EPC, CD133+CD34+EPC, CD34+KDR+EPC were higher in OSA groups than those of control group, both of which were higher in severe OSA group than those of in mild and moderate OSA groups. The levels of ALDHloCD34+KDR+EPC were higher in mild and moderate OSA groups than that of the control groups, and the levels of ALDHloCD34+KDR+EPC were significantly lower in se-vere OSA group than those of control, mild and moderate OSA groups. Serum levels of HIF-1α. VEGF were significantly high-er in OSA groups compared to those in control groups, both of which were higher in severe OSA group than those of mild and moderate OSA groups. Serum levels of SDF-1αwere significantly lower in severe OSA groups than those of mild, moderate OSA and control groups (P中度OSA组>轻度OSA组>对照组(均P中度OSA组>轻度OSA组>对照组,SDF-1α水平为重度OSA组<中度OSA组<轻度OSA组<对照组(均P<0.05).结论 OSA患者可能都会诱导动员并招募大量无效EPC,其数量庞大,但直接参与修复内皮的ALDHloCD34+KDR+EPC并未增加,尤其对于重度OSA患者甚至有可能减

  8. Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development.

    Science.gov (United States)

    Abd El Aziz, M T; Abd El Nabi, E A; Abd El Hamid, M; Sabry, D; Atta, H M; Rahed, L A; Shamaa, A; Mahfouz, S; Taha, F M; Elrefaay, S; Gharib, D M; Elsetohy, Khaled A

    2015-03-01

    We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI. PMID:25750747

  9. Experimental infection with epizootic haematopoietic necrosis virus (EHNV of rainbow trout (Oncorhynchus mykiss Walbaum and European perch (Perca fluviatilis L.

    Directory of Open Access Journals (Sweden)

    Borzym Ewa

    2015-12-01

    Full Text Available The aim of this study was the determination of the susceptibility of Polish farmed redfin perch (Perca fluviatilis L. and rainbow trout (Oncorhynchus mykiss Walbaum to experimental infection with haematopoietic necrosis virus (EHNV. A bath challenge model was tested at two temperature ranges: 13-15°C and 20-22°C. After 7 d, the first clinical signs and mortality were observed in fish kept at these temperatures. Significantly more mortality cases were reported in the redfin perch population, reaching a maximum of 24% compared with 12% in the rainbow trout group at 20-22°C. EHNV was reisolated from redfin perch and rainbow trout tissue in cell culture and the infection was confirmed by a molecular method and histopathology during the duration of the experiment. This study revealed that fish from Polish farms can be susceptible to EHNV even at lower temperatures.

  10. Real-time fluorescent quantitative PCR assay for measuring cytomegalovirus DNA load in patients after haematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    FAN Jun; MA Wei-hang; YANG Mei-fang; XUE Han; GAO Hai-nü; LI Lan-juan

    2006-01-01

    @@ Cytomegalovirus (CMV) infection is a major and often deadly complication of haematopoietic stem cell (HSC) transplantation.1 Successful preemptive CMV therapy in transplant patients depends on the availability of sensitive, specific, and timely diagnostic tests for CMV infections.2 The pp65antigenemia assay has been used for this purposewith considerable success but has disadvantages of being time-consuming and labor-intensive.3 Recently,commercial quantitative polymerase chain reaction (PCR) methods based on TaqMan technique have become available and proven to be useful in the diagnosis of microbial infection as well as the determination of viral load.4 In this study, we developed a fluorescent-based quantitative real-time PCR (RT-FQ PCR) assay using TaqMan chemistry for rapid and quantitative detection of CMV DNA and assessed its clinic value for monitoring the reinfection of CMV in patients after HSC transplantion.

  11. Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis.

    Science.gov (United States)

    Gargett, C E; Schwab, K E; Brosens, J J; Puttemans, P; Benagiano, G; Brosens, I

    2014-07-01

    The pathogenesis of early-onset endometriosis has recently been revisited, sparked by the discovery of endometrial stem/progenitor cells and their possible role in endometriosis, and because maternal pregnancy hormone withdrawal following delivery induces uterine bleeding in the neonate. The neonatal uterus has a large cervix to corpus ratio which is functionally blocked with mucous, supporting the concept of retrograde shedding of neonatal endometrium. Only 5% show overt bleeding. Furthermore, the presence of endometriosis in pre-menarcheal girls and even in severe stage in adolescents supports the theory that early-onset endometriosis may originate from retrograde uterine bleeding soon after birth. Endometrial stem/progenitor cells have been identified in menstrual blood suggesting that they may also be shed during neonatal uterine bleeding. Thus, we hypothesized that stem/progenitor cells present in shedding endometrium may have a role in the pathogenesis of early-onset endometriosis through retrograde neonatal uterine bleeding. During the neonatal and pre-pubertal period, shed endometrial stem/progenitor cells are postulated to survive in the pelvic cavity in the absence of circulating estrogens supported by niche cells also shed during neonatal uterine bleeding. According to this hypothesis, during thelarche, under the influence of rising estrogen levels, endometrial stem/progenitor cells proliferate and establish ectopic endometrial lesions characteristic of endometriosis. This New Research Horizon review builds on recent discussions on the pathogenesis of early-onset endometriosis and raises new avenues for research into this costly condition. PMID:24674992

  12. Proliferative kinetics of the haematopoietic stem cells of the mouse after several weeks of reconvalescence of an irradiation attack

    International Nuclear Information System (INIS)

    The 125IDU(iodo-deoxyuridine) tracer-technique was applied for investigating proliferative kinetics. The intention was to reveal a possible persistent irradiation damage in the haematopoietic stem-cells of the mouse. The three following methodically differing arrangements were made: 1. 35 days after irradiation with 450 rad no difference is found between the measured turnover of incorporated 125IUD in the bone marrow and not irradiated mice. However, there is a splenic cell population which unambiguously transfers its activity slowlier. A dose-response relationship exists to a limited extent. 2. By four transplantations at different instants the donors were marked first, and then the turnover of the early haematopoietic precursor cells in the bone marrow was detected. It resulted that 35 days after irradiation with 450 rad the turnover takes place slightly slowlier than in not irradiated early precursor cells. Iodised water, which is administered before the tracer technique is applied, seems to have a stimulating effect, particularly on the turnover of irradiated stem cells; the marking with a specific activity of 2000 Ci/mol seems to have a slightly toxic effect. 3. A test was developed, by which the proliferation velocity of stem cells and their descendants is measured when there is a very high proliferation stimulus. Differing amounts of bone marrow cells are transfused to lethally irradiated receivers. Within the logarithmic phase of the 125IDU incorporation the relative cellular proliferation, originating in the stem cells being in the spleen, is determined for the interval between day 3 and day 5. It results very clearly that the descendants of those stem cells irradiated with 450 rad after a reconvalescence time of 35 days present a lower degree of rapid proliferative ability than the not irradiated cells. (orig./MG)

  13. A Multipotent Progenitor Domain Guides Pancreatic Organogenesis

    OpenAIRE

    Zhou, Qiao; Law, Anica Chi-Ying; Rajagopal, Jayaraj; Anderson, William J.; Gray, Paul A.; Douglas A Melton

    2007-01-01

    The mammalian pancreas is constructed during embryogenesis by multipotent progenitors, the identity and function of which remain poorly understood. We performed genome-wide transcription factor expression analysis of the developing pancreas to identify gene expression domains that may represent distinct progenitor cell populations. Five discrete domains were discovered. Genetic lineage-tracing experiments demonstrate that one specific domain, located at the tip of the branching pancreatic tre...

  14. Supernova Remnant Progenitor Masses in M31

    CERN Document Server

    Jennings, Zachary G; Murphy, Jeremiah W; Dalcanton, Julianne J; Gilbert, Karoline M; Dolphin, Andrew E; Fouesneau, Morgan; Weisz, Daniel R

    2012-01-01

    Using HST photometry, we age-date 59 supernova remnants (SNRs) in the spiral galaxy M31 and use these ages to estimate zero-age main sequence masses (MZAMS) for their progenitors. To accomplish this, we create color-magnitude diagrams (CMDs) and use CMD fitting to measure the recent star formation history (SFH) of the regions surrounding cataloged SNR sites. We identify any young coeval population that likely produced the progenitor star and assign an age and uncertainty to that population. Application of stellar evolution models allows us to infer the MZAMS from this age. Because our technique is not contingent on precise location of the progenitor star, it can be applied to the location of any known SNR. We identify significant young SF around 53 of the 59 SNRs and assign progenitor masses to these, representing a factor of 2 increase over currently measured progenitor masses. We consider the remaining 6 SNRs as either probable Type Ia candidates or the result of core-collapse progenitors that have escaped ...

  15. The clinical significance of peripheral blood hematopoietic stem/progenitor cell in patients with rheumatoid arthritis%类风湿关节炎患者外周血CD34+造血干/祖细胞的检测及其意义

    Institute of Scientific and Technical Information of China (English)

    陈杰; 钱龙; 秦明明; 汪国生; 李向培

    2010-01-01

    目的 探讨类风湿关节炎(RA)外周血造血干/祖细胞(HSC/HPC)的数量及细胞膜CD34平均荧光强度(MFI)变化及其与临床指标的关系,以期阐明其在RA中的意义.方法 收集34例RA患者和16名健康对照者外周血,利用单克隆抗体标记CD34+细胞,流式方法测定CD34+HSC/HPC所占外周血淋巴细胞的比例及膜CD34的MFI,分析其与外周血细胞计数、疾病活动病程和药物应用的关系.数据分析采用t检验和方差分析,相关性分析采用Pearson相关分析.结果 ①RA患者CD34+细胞在外周血中淋巴细胞中所占的比例比健康人偏低[分别为(0.13±0.09)%和(0.38±0.21)%,P<0.05],但两者所占外周血淋巴细胞的比例均低于0.5%;但MFI偏高(分别为57±33和31±11,P<0.05).②RA患者CD34+细胞在外周血淋巴细胞中所占的比例与外周血红细胞计数、血红蛋白浓度呈正相关性,和C反应蛋白呈负相关;其MFI与健康评价问卷表(HAQ)评分、X线分期呈正相关,与血小板计数呈负相关.③RA患者CD34+细胞在外周血淋巴细胞中所占比例的降低程度以及MFI与疾病的活动性、病程和用药情况无明显相关性(P>0.05).结论 造血干细胞可能在RA的发病机制中起作用.%Objective To measure the number of peripheral blood CD34+ hematopoietic stem/progenitor cells (HSC/HPC) expression of CD34 in the peripheral blood of patients with rheumatoid arthritis and exploreits relationship with clinical manifestations. Methods CD34+ HSC/HPCs in the peripheral blood of RA patients (n=32) and healthy controls (n=16) were detected using flow cytometry. The relationship between the frequency of HSC/HPCs, mean fluorescence intensities (MFI) of CD34 and clinical manifestations and rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibodies, disease activity score (DAS) 28,X rays stages and healthy assessment questionnaire (HAQ) were analyzed. Student's t-test and pearont test were used for

  16. 人脐血造血干/祖细胞的生物反应器大规模扩增及移植实验%Expansion of hematopoietic stem/progenitor cells of cord blood by bioreactor and the transplantation into NOD/SCID mice

    Institute of Scientific and Technical Information of China (English)

    毛平; 段华新; 王彩霞; 李迎霄; 邓婷芬; 许艳丽; 罗畅如

    2009-01-01

    Objective To expand hematopoietic stem/progenitor cells of cord blood in large scale by bioreactor. Methods Mononuclear cells from human umbilical cord blood were cultured in serum-free medium with stem cell factor (SCF), flt-3 ligand (FL3) and thrombopoietin (TPO). The expansion fold of cells, colony-forming and expression of surface molecules were analyzed by cell counting, colony-forming assay and flow cytometry, respectively. And the engraftment of these expanded cells was studied through cell transplantation into irradiated non-obese diabetic/severe-combined immunodeficient (NOD/SCID) mice. Results After culture for 7 days,the folds of total cell expansion in bioreactor were higher than those in static culture, P0.05). The cells expanded in bioreactor were successfully engrafted into irradiated NOD/SCID mice and reconstructed the multi-lineage hematopoiesis. Conclusion The bioreactor favors large-scale expansion of hematopoietic progenitor cells and keeps the hematopoietic repopulation potential.%目的 利用生物反应器大规模扩增人脐血造血干/祖细胞,并通过动物移植实验检验该方法的有效性.方法 采集抗凝脐血10份,分离出单个核细胞(MNC),分别进行生物反应器扩增培养和静态扩增培养.检测扩增前后细胞表面CD34、CD38、CD133、CD184和CD62L分子的表达,并进行造血干/祖细胞集落的培养.取非肥胖糖尿病重症联合免疫缺陷小鼠,以X射线照射后,分为4组,其中MNC组小鼠注射未经扩增培养的MNC;静态扩增组小鼠注射经过静态扩增培养的细胞;反应器扩增组小鼠注射经过生物反应器扩增培养的细胞;空白对照组小鼠注射生理盐水.移植后6周处死存活小鼠,收集骨髓细胞,检测其中CD45+、CD3+、CD19+和CD33+细胞的含量以及人特异的Cart-Ⅰ和Alu基因的表达.结果 生物反应器扩增前MNC为(1.2~2.8)×108个,扩增后为(3.7~12.6)×108个,扩增后的细胞数明显高于静态扩增培养者(P<0

  17. Testosterone Enhances the Proliferation of Peripheral-Blood-Derived Endothelial Progenitor Cells by up-regulating Vascular Endothelial Growth Factor Expression%睾酮通过上调血管内皮生长因子表达促进外周血内皮祖细胞增殖

    Institute of Scientific and Technical Information of China (English)

    薛亚威; 任国庆; 王芝; 孙文文; 张浩

    2013-01-01

    目的 探讨雄激素对外周血内皮祖细胞(PB-EPC,)增殖能力的影响及其可能机制.方法 将健康志愿者外周血经密度梯度离心法分离的单个核细胞接种至人纤维连接蛋白包被的培养板中,EGM-2MV培养7天后,多波长激光共聚焦显微镜鉴定FITC标记的荆豆凝集素和Dil标记的乙酰化低密度脂蛋白双染色阳性为PB-EPC.将贴壁细胞分为5组,前4组分别加入0、1、10、100nmol/L睾酮,第5组加入10 nmol/L雄激素受体阻断剂氟他胺干预3h后,再加10 nmol/L睾酮干预.培养48 h后,MTT比色法检测各组PB-EPC的增殖能力.实时定量PCR检测血管内皮生长因子(VEGF) mRNA的表达变化,ELISA检测VEGF分泌量的变化.结果 睾酮呈浓度依赖性促进EPC增殖,雄激素受体阻断剂氟他胺完全阻断睾酮对EPC的促进作用.与空白对照组相比,睾酮在mRNA和蛋白水平上调PB-EPC的VEGF表达,氟他胺可阻断此作用.结论 睾酮通过雄激素受体途径上调VEGF的表达,促进PB-EPC增殖.%Aim To explore the effects and related mechanisms of testosterone on the proliferation of Peripheral-blood endothelial progenitor cells (PB-EPCs). Methods Total mononuclear cells(MNC) were isolated from peripheral blood of healthy volunteers by Ficoll density gradient centrifugation, culturing with EGM-2MV for 7 days in vitro. The adherent cells showed up taking of acetylated low-density ( ac-LDL-Dil) and binding of lectin ( FITC-UEA-I) , observing with confocal laser scanning microscopy. PB-EPC were dealt with four concentrations of testosterone, as 0 nmol/L, 1 nmol/L, 10 nmol/L,and 100 nmol/L respectively, and in another group PB-EPC were pretreated with 10 nmol/L flutamide (androgen receptor antagonist) for 3h and then stimulated with 10 nmol/L testosterone. After 48 h, the ability of cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diph-phenyltetrazolium bromide assay ( MTT). The VEGF expression was tested by quantitative real

  18. Blood Clots

    Science.gov (United States)

    ... Index A-Z Blood Clots Blood clots are semi-solid masses of blood that can be stationary (thrombosis) ... treated? What are blood clots? Blood clots are semi-solid masses of blood. Normally, blood flows freely through ...

  19. Tracking erythroid progenitor cells in times of need and times of plenty.

    Science.gov (United States)

    Koury, Mark J

    2016-08-01

    Red blood cell production rates increase rapidly following blood loss or hemolysis, but the expansion of erythropoiesis in these anemic states is tightly regulated such that rebound polycythemia does not occur. The erythroid cells that respond to erythropoietic stimulation or suppression are the progenitor stages of burst-forming units-erythroid (BFU-Es) and colony-forming units-erythroid (CFU-Es). Results from an early study of the changes in the size, location, and cell cycling status of BFU-E and CFU-E populations in mice under normal conditions, erythropoietic stimulation, and erythropoietic suppression are used as reference points to review subsequent developments related to erythroid progenitor populations and regulation of their size. The review concerns development of erythroid progenitor populations mainly in mice and humans, with a focus on the mechanisms related to the rapid but highly regulated expansion of erythropoiesis in spleens of erythropoietically stimulated mice. Current knowledge is used as a model of erythroid progenitor populations in mice under normal, erythropoietically suppressed, and erythropoietically stimulated conditions. Clinical applications of information learned from studies of erythropoietic expansion, in terms of current therapies for anemia, are reviewed. PMID:26646992

  20. Drosophila: a model for studying genetic and molecular aspects of haematopoiesis and associated leukaemias

    Directory of Open Access Journals (Sweden)

    Michèle Crozatier

    2011-07-01

    Full Text Available Vertebrate haematopoietic stem cells (HSCs give rise to a hierarchically organised set of progenitors for erythroid, myeloid, lymphoid and megakaryocyte lineages, and are responsible for lifelong maintenance of the blood system. Dysregulation of the haematopoietic differentiation programme is at the origin of numerous pathologies, including leukaemias. With the discoveries that many transcriptional regulators and signalling pathways controlling blood cell development are conserved between humans and Drosophila melanogaster, the fruit fly has become a good model for investigating the mechanisms underlying the generation of blood cell lineages and blood cell homeostasis. In this review article, we discuss how genetic and molecular studies of Drosophila haematopoiesis can contribute to our understanding of the haematopoietic niche, as well as of the origin and/or progression of haematopoietic malignancies in humans.

  1. 不同胎龄早产儿脐带血中内皮祖细胞水平及迁移能力研究%Research of number and migration ability of endothelial progenitor cells isolated from umbilical cord blood in preterm infants with different gestational ages

    Institute of Scientific and Technical Information of China (English)

    倪美艳; 白小红; 陈娟; 陈大鹏

    2016-01-01

    Objective To investigate the differences of the number and migration ability of endothelial progenitor cell (EPC ) isolated from umbilical cord blood among preterm infants with different gestational ages .Methods From October 2014 to July 2015 ,a total of 47 cases of umbilical cord blood of neonates in West China Second University Hospital , Sichuan University , Sichuan Academy of Medical Sciences & Sichuan Provincial People′s Hospital ,and Chengdu First People′s Hospital were chosen into this study .According to the gestational age of newborns whose umbilical cord blood was collected ,they were divided into very preterm group ( the gestational ages were 28 to 32 weeks ,n=12) ,preterm group (the gestational ages were 32 to 36 weeks ,n=20) ,and full‐term group (the gestational ages were > 37 weeks ,n=15) .Before the induced differentiation of umbilical cord blood in the three groups ,flow cytometry was used to detect the level of EPC .After the induced differentiation of umbilical cord blood in the three groups ,the mononuclear cells were incubated and stained by fluorescent probes labeled Dil‐acetylated low‐density lipoprotein (Dil‐Ac‐LDL ) and fluorescein isothiocyanate‐labeled ulex europaeus agglutinin‐1 (FITC‐UEA‐1 ) . The stainings of mononuclear cells in the three groups were observed under fluorescence microscope to detect whether the EPC was successfully induced or not .Transwell migration assay was used to detect the migration ability of EPC in the three groups .The levels of EPC before the induced differentiation of umbilical cord blood in three groups and the migration numbers of EPC after the induced differentiation of umbilical cord blood in three groups were compared by statistical methods .The study protocol was approved by the Ethical Review Boards of three hospitals from which the umbilical cord blood was collected .Informed consent was obtained from each pregnant woman before obtaining umbilical cord blood .There were no

  2. Nutritional status and its impact on outcome in patients undergoing allogeneic haematopoietic cell transplantation and an experimental trial to improve the supply of a specific micronutrient

    OpenAIRE

    Urbain, Paul

    2012-01-01

    The first two studies investigated the course of the nutritional status in patients un-dergoing allogeneic haematopoietic cell transplantation (alloHCT) and the validity of nutritional markers as independent risk factors for outcome. In line with others, we detected an overall good nutritional status before alloHCT by employing quick screening tools such as BMI and the SGA questionnaire for identifying malnutrition. However, upon closer inspection, we observed unintentional weight loss previo...

  3. Less veno-occlusive disease after intravenous versus oral busulfan for autologous haematopoietic stem cell transp.l antation: the Belgian paediatric experlence

    OpenAIRE

    Huybrechts, S; Beguin, Yves; Bordon, V; DRESSE, Marie-Françoise; Dupont, S.; Ferster, A; Laureys, G.; Meyts, I.; Renard, M; Vermylen, C

    2012-01-01

    Busulfan is commonly used in preparative conditioning regimens prior to haematopoietic stem cell transplantation in children and young adults for malignant and non-malignant disorders. For many years busulfan was only available in oral form, resulting in large inter- and intra-patients variability in plasma exposure, associated with higher graft failure rate as weil as higher toxicity such as veno-occlusive disease. With the development of an intravenous formulation of busulfan, a more acc...

  4. Effects of Simian Betaretrovirus Serotype 1 (SRV1) Infection on the Differentiation of Hematopoietic Progenitor Cells (CD34+) Derived from Bone Marrow of Rhesus Macaques (Macaca mulatta)

    Science.gov (United States)

    Montiel, Nestor A; Todd, Patricia A; Yee, JoAnn; Lerche, Nicholas W

    2012-01-01

    Peripheral blood cytopenias, particularly persistent anemia and neutropenia, are commonly associated with simian betaretrovirus infection of Asian monkeys of the genus Macaca. The pathogenetic mechanisms underlying these hematologic abnormalities are not well understood. The current study investigated the in vitro tropism of simian betaretrovirus (SRV) for both hematopoietic progenitor (CD34+) and stromal cells obtained from rhesus macaque bone marrow and assessed the effects of infection on hematopoietic progenitor cell differentiation in vitro. After in vitro exposure, SRV proviral DNA could be demonstrated by real-time PCR in cells and the reverse transcriptase assay in supernatants from SRV-exposed progenitor-associated stroma, but not in differentiated colonies derived from SRV-exposed progenitors. Furthermore, in vitro exposure involving cell–cell contact of uninfected CD34+ progenitor cells with SRV-infected stromal cells resulted in a statistically significant reduction in granulocyte–macrophage colony formation in absence of detectable SRV-infection of progenitor cells. Reduction in colony formation occurred in a ‘dose-dependent’ fashion with increasing contact time. No effects on erythroid lineages and RBC differentiation were noted. Our results suggest that hematologic abnormalities observed during SRV disease (natural or experimental) of rhesus macaques may not result from direct effects of viral infection of progenitor cell populations, but rather be (at least in part) a consequence of SRV infection of supportive bone marrow stroma with secondary effects on differentiation of associated progenitor cells. PMID:22330653

  5. Mobilized progenitor cells as a bridging therapy for radiation casualties: a brief review of tocopherol succinate-based approaches.

    Science.gov (United States)

    Singh, Vijay K; Singh, Pankaj K; Wise, Stephen Y; Seed, Thomas M

    2011-07-01

    Nuclear detonation through either military or terrorist action would most likely lead to a mass-casualty scenario involving victims with varying degrees of exposure to ionizing radiation. As a result of radiation injury to the hematopoietic system, victims would suffer from a lack of red blood cells that deliver oxygen, immune cells that detect and eliminate infectious agents, and blood platelets that promote blood clot formation. In part, these symptoms are generally referred to as acute radiation syndrome (ARS). While some victims of moderate to high levels of radiation will be beyond saving, most will have received enough radiation to injure but not kill their bone marrow cells completely. Such people will recover from their injuries but face a 30-60day period during which they cannot fully fight infections and are prone to uncontrolled bleeding and anemia. To keep them alive until their hematopoietic system recovers, they must receive supportive care. Recently, using experimental animal models of ARS, transfusion of myeloid progenitor cells have been tried as a bridging therapy for radiation-exposed animals. Such cells have been shown to be effective in protecting animals exposed to lethal doses of radiation. These myeloid progenitors (along with of other hematopoietic progenitor cell types) can be mobilized out of the bone marrow into the blood for the reconstitution of hematopoiesis. This review discusses various approaches to the mobilization of progenitors using different mobilizing agents, and their utility as a bridging therapy for radiation casualties. We suggest that α-tocopherol succinate (TS) is an optimal mobilizing agent for progenitors. The extent of progenitor mobilization TS elicits in experimental mice is comparable to clinically used drugs such as recombinant granulocyte-colony stimulating factor rhG-CSF/Neupogen® and the bicyclam AMD3100 (plerixafor/Mozobil); therefore, we propose that TS be considered for further translational development

  6. Progenitors of core-collapse supernovae

    CERN Document Server

    Smartt, Stephen J

    2009-01-01

    Knowledge of the progenitors of core-collapse supernovae is a fundamental component in understanding the explosions. The recent progress in finding such stars is reviewed. The minimum initial mass that can produce a supernova has converged to 8 +/- 1 solar masses, from direct detections of red supergiant progenitors of II-P SNe and the most massive white dwarf progenitors, although this value is model dependent. It appears that most type Ibc supernovae arise from moderate mass interacting binaries. The highly energetic, broad-lined Ic supernovae are likely produced by massive, Wolf-Rayet progenitors. There is some evidence to suggest that the majority of massive stars above ~20 solar masses may collapse quietly to black-holes and that the explosions remain undetected. The recent discovery of a class of ultra-bright type II supernovae and the direct detection of some progenitor stars bearing luminous blue variable characteristics suggests some very massive stars do produce highly energetic explosions. The phys...

  7. 脐血单个核细胞来源红系祖细胞的诱导扩增及保存的研究%The induction and cryopreservation of erythroid progenitor cells derived from umbilical cord blood mononuclear cells

    Institute of Scientific and Technical Information of China (English)

    陈琳; 范增; 裴雪涛; 谢小燕; 习佳飞; 吕洋; 田宇; 刘大庆岳文; 李艳华; 南雪; 李思婷

    2016-01-01

    Objective To discover the techniques for ex vivo generation and cryopreservation of erythroid progenitor cells(EPCs)derived from umbilical cord blood(UCB)mononuclear cells(MNCs). Methods UCB was chosen as the source of EPCs. Erythrocytes were precipitated by hydroxyethyl starch (HES). MNCs were separated by Ficoll density gradient centrifugation. Erythroid progenitor cell were generated from MNC ex vivo in suspension culture supplemented with stem cell growth factor, insulin growth factor, erythropoietin, Fms- liketyrosinekinase ligand, transferrin and dexamethasone. Cell maturation was evaluated by morphologic analysis and CD71/CD235a expression profiling. In vitro induced cells were cryopreserved using different cryopreservation media. The cell survival rate, phenotype and proliferation curves were detected after cell thawing. Results With the extension of culture time, the total number of cells increased significantly accompanied with the elevation of CD71 and CD235 positive populations. After 14-day inducing, the cells reached to approximately 110 times of the starting number with the cell viability as(88.92±0.95)%. The percentages of cell surface markers were(86.77±9.11)%forCD71 and(64.47 ± 16.67)% for CD71/CD235, respectively. With the extension of inducing time, wright-Giemsa staining showed that the middle erythroblasts appeared mostly at day 10, and the late erythroblasts were seen at day 14. The red pellets were present at day 14, which indicated the more production of hemoglobin. Colony forming assay showed that erythroid colonies at induction day 7 were higher than that for non-induced cells(326.00 ± 97.96 vs 61.60 ± 20.03 per 2 000 cells). With the extension of culture time, the number of erythroid colonies decreased. Induced EPCs were preserved with different cryopreservation solutions, in which 10%DMSO were better than 5%DMSO. Additionally, 10%DMSO+2%HSA showed no different with 10% DMSO + 5% HSA. Combined 50% plasma with 2% HSA was more

  8. Hematopoietic stem/progenitor cells of cord blood expanded at large scale by magnet stirred culture and engrafted intoNOD/SCIDmice%人脐血造血干/祖细胞的磁力搅拌悬浮培养及移植实验

    Institute of Scientific and Technical Information of China (English)

    段华新; 毛平; 罗畅如; 许艳丽; 谢健晋; 张玉平

    2009-01-01

    目的 探讨磁搅拌大规模培养体系对人脐血造血祖细胞的扩增效果以及扩增的人造血祖细胞植入动物体内后的造血重建情况.方法 从新鲜抗凝脐血中分离出单个核细胞(MNC),以添加干细胞因子、酪氨酸激酶受体3配基及血小板生成素的无血清培养体系进行培养.静态扩增组的细胞置于T25培养瓶中培养,磁搅拌悬浮扩增组(磁搅拌扩增组)的细胞采用Celstir装置进行培养,培养体系为50~100 ml.培养7 d后进行细胞计数、集落培养检测和细胞表面分子表达的测定.以不进行培养者为对照组.非肥胖糖尿病重症联合免疫缺陷(NOD/SCID)小鼠在接受2.5 Gy的亚致死剂量X射线照射后分别从尾静脉输入上述静态扩增组、磁搅拌扩增组和对照组的MNC(5×106个),另设不移植的空白对照组.观察小鼠的存活情况,6周后处死存活小鼠,检测骨髓细胞中CD34+细胞、CD3+细胞、CD19+细胞、CD33+细胞及CD45+细胞的含量以及人特异的Cart-Ⅰ和Alu基因的表达.结果 经过7天的培养,磁搅拌扩增组的造血祖细胞扩增倍数为(2.8±0.45)倍,明显高于静态扩增组的(2.1±0.48)倍(P0.05).存活6周的小鼠,其骨髓中能检人特异性CD34+细胞,以及CD3+细胞、CD19+细胞、CD33+细胞及CD45+细胞,也检测到人Alu基因和Cart-Ⅰ基因的表达.结论 磁搅拌培养能大规模扩增脐带血造血祖细胞,扩增的细胞能植入x射线照射的NOD/SCID小鼠,并重建其多系造血.%Objective To expand hematopoietic stem/progenitor cells at large scale in magnet stirred culture system. Methods Mononuclear cells from human umbilical cord blood were cultured in serum-free medium supplemented with stem cell factor (SCF), fh-3 ligand (FL3) and thrombopoietin (TPO). The expansion fold of cells, colony-forming and expression of surface molecules were studied in magnet stirred culture by cell counting, colony-forming assay and flow cytometry. And the

  9. Fractalkine expression induces endothelial progenitor cell lysis by natural killer cells.

    Directory of Open Access Journals (Sweden)

    Dilyana Todorova

    Full Text Available BACKGROUND: Circulating CD34(+ cells, a population that includes endothelial progenitors, participate in the maintenance of endothelial integrity. Better understanding of the mechanisms that regulate their survival is crucial to improve their regenerative activity in cardiovascular and renal diseases. Chemokine-receptor cross talk is critical in regulating cell homeostasis. We hypothesized that cell surface expression of the chemokine fractalkine (FKN could target progenitor cell injury by Natural Killer (NK cells, thereby limiting their availability for vascular repair. METHODOLOGY/PRINCIPAL FINDINGS: We show that CD34(+-derived Endothelial Colony Forming Cells (ECFC can express FKN in response to TNF-α and IFN-γ inflammatory cytokines and that FKN expression by ECFC stimulates NK cell adhesion, NK cell-mediated ECFC lysis and microparticles release in vitro. The specific involvement of membrane FKN in these processes was demonstrated using FKN-transfected ECFC and anti-FKN blocking antibody. FKN expression was also evidenced on circulating CD34(+ progenitor cells and was detected at higher frequency in kidney transplant recipients, when compared to healthy controls. The proportion of CD34(+ cells expressing FKN was identified as an independent variable inversely correlated to CD34(+ progenitor cell count. We further showed that treatment of CD34(+ circulating cells isolated from adult blood donors with transplant serum or TNF-α/IFN-γ can induce FKN expression. CONCLUSIONS: Our data highlights a novel mechanism by which FKN expression on CD34(+ progenitor cells may target their NK cell mediated killing and participate to their immune depletion in transplant recipients. Considering the numerous diseased contexts shown to promote FKN expression, our data identify FKN as a hallmark of altered progenitor cell homeostasis with potential implications in better evaluation of vascular repair in patients.

  10. Common molecular pathways involved in human CD133+/CD34+ progenitor cell expansion and cancer

    Directory of Open Access Journals (Sweden)

    Vêncio Ricardo Z

    2007-06-01

    Full Text Available Abstract Background Uncovering the molecular mechanism underlying expansion of hematopoietic stem and progenitor cells is critical to extend current therapeutic applications and to understand how its deregulation relates to leukemia. The characterization of genes commonly relevant to stem/progenitor cell expansion and tumor development should facilitate the identification of novel therapeutic targets in cancer. Methods CD34+/CD133+ progenitor cells were purified from human umbilical cord blood and expanded in vitro. Correlated molecular changes were analyzed by gene expression profiling using microarrays covering up to 55,000 transcripts. Genes regulated during progenitor cell expansion were identified and functionally classified. Aberrant expression of such genes in cancer was indicated by in silico SAGE. Differential expression of selected genes was assessed by real-time PCR in hematopoietic cells from chronic myeloid leukemia patients and healthy individuals. Results Several genes and signaling pathways not previously associated with ex vivo expansion of CD133+/CD34+ cells were identified, most of which associated with cancer. Regulation of MEK/ERK and Hedgehog signaling genes in addition to numerous proto-oncogenes was detected during conditions of enhanced progenitor cell expansion. Quantitative real-time PCR analysis confirmed down-regulation of several newly described cancer-associated genes in CD133+/CD34+ cells, including DOCK4 and SPARCL1 tumor suppressors, and parallel results were verified when comparing their expression in cells from chronic myeloid leukemia patients Conclusion Our findings reveal potential molecular targets for oncogenic transformation in CD133+/CD34+ cells and strengthen the link between deregulation of stem/progenitor cell expansion and the malignant process.

  11. Circulating Endothelial Progenitor Cell and Platelet Microparticle Impact on Platelet Activation in Hypertension Associated with Hypercholesterolemia

    OpenAIRE

    Nicoleta Alexandru; Doina Popov; Emanuel Dragan; Eugen Andrei; Adriana Georgescu

    2013-01-01

    AIM: The purpose of this project was to evaluate the influence of circulating endothelial progenitor cells (EPCs) and platelet microparticles (PMPs) on blood platelet function in experimental hypertension associated with hypercholesterolemia. METHODS: Golden Syrian hamsters were divided in six groups: (i) control, C; (ii) hypertensive-hypercholesterolemic, HH; (iii) 'prevention', HHin-EPCs, HH animals fed a HH diet and treated with EPCs; (iv) 'regression', HHfin-EPCs, HH treated with EPCs aft...

  12. 铁过载对脐带血来源的造血干祖细胞及造血支持细胞的作用观察%Effect of iron overload on umbilical cord blood derived hematopoietic stem/progenitor cells and hematopoietic supportive cells

    Institute of Scientific and Technical Information of China (English)

    肖霞; 赵明峰; 卢文艺; 柴笑; 穆娟; 邓琦; 李青; 李玉明

    2013-01-01

    目的 探讨铁过载对脐带血(UCB)来源的造血干祖细胞及造血支持细胞,尤其是间充质干细胞(MSCs)的损伤作用.方法 体外培养脐带血单个核细胞(UCB-MNCs)和脐带血间充质干细胞(UCB-MSCs),向培养液中添加200 μmol/L的枸橼酸铁胺(FAC) 24 h建立铁过载模型.分为MNCs-CTL组、MNCs-FAC组、MSCs-CTL组、MSCs-FAC组,每组设3个复孔,实验重复3次.检测细胞内活性氧物质(ROS)水平变化、细胞增殖、分化、凋亡以及造血支持作用.结果 对UCB-MNCs进行铁过载,MNCs-FAC组造血集落形成单位(CFU-E、CFU-GM、BFU-E、CFU-mix)计数显著低于MNCs-CTL组(P<0.05),MNCs-FAC组造血干细胞(CD+34)、髓系造血细胞(CD+33)、红系造血细胞(GlyA+)比例及计数均显著低于MNCs-CTL组(P均<0.05);MNCs-FAC组的凋亡率高于MNCs-CTL组(P<0.05).MSCs-FAC组的群体倍增时间明显长于MSCs-CTL组,且其凋亡率亦高于MSCs-CTL组(P<0.05).结论 铁过载可抑制造血干祖细胞的增殖、分化,诱导其凋亡,也可抑制MSCs的增殖能力,诱导其凋亡,降低其造血支持能力,且此过程中ROS升高.%Objective To explore the detrimental effect of iron overload on umbilical-cord blood (UCB) derived hematopoietic stem/progenitor cells (HSPCs) and hematopoietic supportive cells,especially mesenchymal stem cells (MSCs).Methods Iron overload model of UCB-MNCs and UCB-MSCs was successfully established by adding 200? mol/L FAC into the culture medium for 12h.Then the reactive oxygen species (ROS) level,cell proliferation,cell differentiation,apoptosis and hematopoietic supportive capability were detected respectively.Results Iron overload was conducted on the UCB-MNCs.The hematopoietic colony forming units (CFU-E,CFU-GM,BFU-E,CFU-mix) counts in the MNCs-FAC group were significantly lower than those of MNCs-CTL group (P < 0.05) ; CD+34,CD3+33,GlyA + cell ratio and counts in the MNCs-FAC group were significantly lower than those in the MNCs-CTL (all P

  13. [Marrow donor registration and cord blood banking: current issues].

    Science.gov (United States)

    Takanashi, Minoko

    2016-03-01

    Marrow donor registration and cord blood banking are essential components of the infrastructure required for unrelated haemopoietic stem cell transplantations. We now have a new law to support and regulate the Marrow Donor Coordination Agency, Cord Blood Banks and the Haematopoietic Stem Cell Provision Support Organization. We also need to have a specific goal for bone marrow and peripheral blood stem cell donor registration, a minimum cord blood bank size, and the demographic data to back the medical needs for unrelated haemopoietic stem cell transplantations. To improve bone marrow and peripheral blood stem cell transplantations, we need to recruit younger adults for marrow registration and make greater efforts to shorten the coordinating period. For cord blood transplantations, uniting and empowering the cord blood collection sites is needed, to encourage and motivate obstetricians and other staff, as the quality of cord blood units is primarily determined during collection. Also, the cord blood banks must work cooperatively to provide cord blood internationally, which includes coordinating with international agencies and their regulations.

  14. Obstructive sleep apnea and endothelial progenitor cells

    Directory of Open Access Journals (Sweden)

    Wang Q

    2013-10-01

    Full Text Available Qing Wang,1,* Qi Wu,2,* Jing Feng,3,4 Xin Sun5 1The Second Respiratory Department of the First People's Hospital of Kunming, Yunnan, People's Republic of China; 2Tianjin Haihe Hospital, Tianjin, People's Republic of China; 3Respiratory Department of Tianjin Medical University General Hospital, Tianjin, People's Republic of China; 4Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, NC, USA; 5Respiratory Department of Tianjin Haihe Hospital, Tianjin, People's Republic of China *These authors contributed equally to this work Background: Obstructive sleep apnea (OSA occurs in 4% of middle-aged men and 2% of middle-aged women in the general population, and the prevalence is even higher in specific patient groups. OSA is an independent risk factor for a variety of cardiovascular diseases. Endothelial injury could be the pivotal determinant in the development of cardiovascular pathology in OSA. Endothelial damage ultimately represents a dynamic balance between the magnitude of injury and the capacity for repair. Bone marrow–derived endothelial progenitor cells (EPCs within adult peripheral blood present a possible means of vascular maintenance that could home to sites of injury and restore endothelial integrity and normal function. Methods: We summarized pathogenetic mechanisms of OSA and searched for available studies on numbers and functions of EPCs in patients with OSA to explore the potential links between the numbers and functions of EPCs and OSA. In particular, we tried to elucidate the molecular mechanisms of the effects of OSA on EPCs. Conclusion: Intermittent hypoxia cycles and sleep fragmentation are major pathophysiologic characters of OSA. Intermittent hypoxia acts as a trigger of oxidative stress, systemic inflammation, and sympathetic activation. Sleep fragmentation is associated with a burst of sympathetic activation and systemic inflammation. In most studies, a reduction in circulating EPCs has

  15. How do I perform hematopoietic progenitor cell selection?

    Science.gov (United States)

    Avecilla, Scott T; Goss, Cheryl; Bleau, Sharon; Tonon, Jo-Ann; Meagher, Richard C

    2016-05-01

    Graft-versus-host disease remains the most important source of morbidity and mortality associated with allogeneic stem cell transplantation. The implementation of hematopoietic progenitor cell (HPC) selection is employed by some stem cell processing facilities to mitigate this complication. Current cell selection methods include reducing the number of unwanted T cells (negative selection) and/or enriching CD34+ hematopoietic stem/progenitors (positive selection) using immunomagnetic beads subjected to magnetic fields within columns to separate out targeted cells. Unwanted side effects of cell selection as a result of T-cell reduction are primary graft failure, increased infection rates, delayed immune reconstitution, possible disease relapse, and posttransplant lymphoproliferative disease. The Miltenyi CliniMACS cell isolation system is the only device currently approved for clinical use by the Food and Drug Administration. It uses magnetic microbeads conjugated with a high-affinity anti-CD34 monoclonal antibody capable of binding to HPCs in marrow, peripheral blood, or umbilical cord blood products. The system results in significantly improved CD34+ cell recoveries (50%-100%) and consistent 3-log CD3+ T-cell reductions compared to previous generations of CD34+ cell selection procedures. In this article, the CliniMACS procedure is described in greater detail and the authors provide useful insight into modifications of the system. Successful implementation of cell selection procedures can have a significant positive clinical effect by greatly increasing the pool of donors for recipients requiring transplants. However, before a program implements cell selection techniques, it is important to consider the time and financial resources required to properly and safely perform these procedures. PMID:26919388

  16. X Inactivation and Progenitor Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruben Agrelo

    2011-04-01

    Full Text Available In mammals, silencing of one of the two X chromosomes is necessary to achieve dosage compensation. The 17 kb non-coding RNA called Xist triggers X inactivation. Gene silencing by Xist can only be achieved in certain contexts such as in cells of the early embryo and in certain hematopoietic progenitors where silencing factors are present. Moreover, these epigenetic contexts are maintained in cancer progenitors in which SATB1 has been identified as a factor related to Xist-mediated chromosome silencing.

  17. Pigment Cell Progenitors in Zebrafish Remain Multipotent through Metamorphosis.

    Science.gov (United States)

    Singh, Ajeet Pratap; Dinwiddie, April; Mahalwar, Prateek; Schach, Ursula; Linker, Claudia; Irion, Uwe; Nüsslein-Volhard, Christiane

    2016-08-01

    The neural crest is a transient, multipotent embryonic cell population in vertebrates giving rise to diverse cell types in adults via intermediate progenitors. The in vivo cell-fate potential and lineage segregation of these postembryonic progenitors is poorly understood, and it is unknown if and when the progenitors become fate restricted. We investigate the fate restriction in the neural crest-derived stem cells and intermediate progenitors in zebrafish, which give rise to three distinct adult pigment cell types: melanophores, iridophores, and xanthophores. By inducing clones in sox10-expressing cells, we trace and quantitatively compare the pigment cell progenitors at four stages, from embryogenesis to metamorphosis. At all stages, a large fraction of the progenitors are multipotent. These multipotent progenitors have a high proliferation ability, which diminishes with fate restriction. We suggest that multipotency of the nerve-associated progenitors lasting into metamorphosis may have facilitated the evolution of adult-specific traits in vertebrates. PMID:27453500

  18. Control of AC133/CD133 and impact on human hematopoietic progenitor cells through nucleolin.

    Science.gov (United States)

    Bhatia, S; Reister, S; Mahotka, C; Meisel, R; Borkhardt, A; Grinstein, E

    2015-11-01

    AC133 is a prominent surface marker of CD34+ and CD34- hematopoietic stem/progenitor cell (HSPC) subsets. AC133+ HSPCs contain high progenitor cell activity and are capable of hematopoietic reconstitution. Furthermore, AC133 is used for prospective isolation of tumor-initiating cells in several hematological malignancies. Nucleolin is a multifunctional factor of growing and cancer cells, which is aberrantly active in certain hematological neoplasms, and serves as a candidate molecular target for cancer therapy. Nucleolin is involved in gene transcription and RNA metabolism and is prevalently expressed in HSPCs, as opposed to differentiated hematopoietic tissue. The present study dissects nucleolin-mediated activation of surface AC133 and its cognate gene CD133, via specific interaction of nucleolin with the tissue-dependent CD133 promoter P1, as a mechanism that crucially contributes to AC133 expression in CD34+ HSPCs. In mobilized peripheral blood (MPB)-derived HSPCs, nucleolin elevates colony-forming unit (CFU) frequencies and enriches granulocyte-macrophage CFUs. Furthermore, nucleolin amplifies long-term culture-initiating cells and also promotes long-term, cytokine-dependent maintenance of hematopoietic progenitor cells. Active β-catenin, active Akt and Bcl-2 levels in MPB-derived HSPCs are nucleolin-dependent, and effects of nucleolin on these cells partially rely on β-catenin activity. The study provides new insights into molecular network relevant to stem/progenitor cells in normal and malignant hematopoiesis. PMID:26183533

  19. Rapid Construction of EGFP Labled Recombinant Adenovirus Containing hVEGF165 and Its Expression in Haematopoietic Cells

    Institute of Scientific and Technical Information of China (English)

    仲照东; 邹萍; 黄士昂; 胡中波; 刘凌波; 卢运萍

    2003-01-01

    By using AdEasy system, which is based on the homologous recombination in bacteria, an EGFP labeled recombinant adenovirus vector containing hVEGF165 was constructed quickly and efficiently expressed in mouse haematopoietic cells. First, hVEGF165 coding sequence was subcloned into shuttle plasmid pAdTrack-CMV, then cotransformed with adenoviral backbone vector pAdEasy-1 into E. coli strain BJ5183. The recombinant adenoviral plasmid was transfected into HEK293 cells to assembly replication-defective adenovirus Ad-EGFP/hVEGF165. The expression of EGFP could be easily detected. The rate of EGFP positive mouse bone marrow mononuclear cells by flow cytometric analysis was 27.3 % (MOI= 100), and the expression of hVEGF165 protein in the supernatant was (1385+332) pg/106 cells. These results suggest that the construction of adenovirus vector by homologous recombination in bacteria features high efficiency and simplicity. The prepared high titer AdEGFP/hVEGF165 can be used an efficient helpful vector to infect hematopoietic cells.

  20. Treosulfan-based conditioning regimens for allogeneic haematopoietic stem cell transplantation in children with non-malignant diseases.

    Science.gov (United States)

    Slatter, M A; Boztug, H; Pötschger, U; Sykora, K-W; Lankester, A; Yaniv, I; Sedlacek, P; Glogova, E; Veys, P; Gennery, A R; Peters, C

    2015-12-01

    An increasing number of children with non-malignant diseases can be cured by allogeneic haematopoietic stem cell transplantation (HSCT). Treosulfan (L-treitol-1,4-bis-methanesulfonate) is being used more frequently for conditioning, owing to its' lower toxicity profile compared with conventional myeloablative regimens. A retrospective analysis was performed of children registered in the EBMT database, who received treosulfan before HSCT between January 2005 and 2010, to identify possible dose-related toxicity and determine the incidence of engraftment, treatment-related mortality and overall survival (OS). Results from 316 transplants from 11 different countries are presented. Ninety-five (30%) were under 1 year of age at the time of transplant. OS was 83% and event-free survival was 76%; 3-year OS and event-free survival of infants below 1 year were 79% and 73%, respectively. No association was found with age at transplant, dose of treosulfan given, other agents used in combination with treosulfan, donor type, stem cell source, or second or subsequent transplant. In this report of the largest number of children to date receiving treosulfan for non-malignant diseases, treosulfan is shown to be a safe and effective agent even for those under 1 year of age at the time of transplant. Further prospective studies are needed using precisely defined protocols with pharmacokinetic monitoring and detailed chimerism analysis. In addition, long-term studies will be vital to determine long-term effects, for example, on fertility in comparison with other regimens.

  1. In vivo identification of periodontal progenitor cells.

    Science.gov (United States)

    Roguljic, H; Matthews, B G; Yang, W; Cvija, H; Mina, M; Kalajzic, I

    2013-08-01

    The periodontal ligament contains progenitor cells; however, their identity and differentiation potential in vivo remain poorly characterized. Previous results have suggested that periodontal tissue progenitors reside in perivascular areas. Therefore, we utilized a lineage-tracing approach to identify and track periodontal progenitor cells from the perivascular region in vivo. We used an alpha-smooth muscle actin (αSMA) promoter-driven and tamoxifen-inducible Cre system (αSMACreERT2) that, in combination with a reporter mouse line (Ai9), permanently labels a cell population, termed 'SMA9'. To trace the differentiation of SMA9-labeled cells into osteoblasts/cementoblasts, we utilized a Col2.3GFP transgene, while expression of Scleraxis-GFP was used to follow differentiation into periodontal ligament fibroblasts during normal tissue formation and remodeling following injury. In uninjured three-week-old SMA9 mice, tamoxifen labeled a small population of cells in the periodontal ligament that expanded over time, particularly in the apical region of the root. By 17 days and 7 weeks after labeling, some SMA9-labeled cells expressed markers indicating differentiation into mature lineages, including cementocytes. Following injury, SMA9 cells expanded, and differentiated into cementoblasts, osteoblasts, and periodontal ligament fibroblasts. SMA9-labeled cells represent a source of progenitors that can give rise to mature osteoblasts, cementoblasts, and fibroblasts within the periodontium. PMID:23735585

  2. Binary progenitor models of type IIb supernovae

    NARCIS (Netherlands)

    Claeys, J.S.W.A.; de Mink, S.E.; Pols, O.R.; Eldridge, J.J.; Baes, M.

    2011-01-01

    Massive stars that lose their hydrogen-rich envelope down to a few tenths of a solar mass explode as extended type IIb supernovae, an intriguing subtype that links the hydrogen-rich type II supernovae with the hydrogen-poor type Ib and Ic. The progenitors may be very massive single stars that lose t

  3. GRB 011121 A Massive Star Progenitor

    CERN Document Server

    Price, P A; Reichart, D E; Kulkarni, S R; Subramanian, R; Wark, R M; Wieringa, M H; Frail, D A; Bailey, J; Boyle, B; Corbett, E A; Gunn, K; Ryder, S D; Seymour, N; Koviak, K; McCarthy, P; Phillips, M; Axelrod, T S; Bloom, J S; Djorgovski, S G; Fox, D W; Galama, T J; Harrison, F A; Hurley, K; Sari, R; Schmidt, B P; Yost, S A; Brown, M J I; Cline, T; Frontera, F; Guidorzi, C; Montanari, E

    2002-01-01

    Of the cosmological gamma-ray bursts, GRB 011121 has the lowest redshift, z=0.36. More importantly, the multi-color excess in the afterglow detected in the Hubble Space Telescope (HST) light curves is compelling observational evidence for an underlying supernova. Here we present near-infrared and radio observations of the afterglow. We undertake a comprehensive modeling of these observations and those reported in the literature and find good evidence favoring a wind-fed circumburst medium. In detail, we infer the progenitor had a mass loss rate of Mdot ~ 10^-7 / v_w3 Mo/yr where v_w3 is the speed of the wind from the progenitor in units of 10^3 km/s. This mass loss rate is similar to that inferred for the progenitor of SN 1998bw which has been associated with GRB 980425. Our data, taken in conjunction with the HST results of Bloom et al. (2002), provide a consistent picture: the long duration GRB 011121 had a massive star progenitor which exploded as a supernova at about the same time as the GRB event.

  4. 氯吡格雷对人早期内皮祖细胞黏附、迁移及增殖功能的影响%Effects of clopidogrel on the adherence, migration and proliferation of early endothelial progenitor cells from human peripheral blood

    Institute of Scientific and Technical Information of China (English)

    李鹏; 刘文娴; 张丽洁; 辛毅

    2012-01-01

    目的 探讨氯吡格雷对人早期内皮祖细胞(EPCs)黏附、迁移及增殖功能的影响.方法 体外培养人外周血早期EPCs并进行鉴定;将含不同浓度(1×10-3~200×10-3 mmol·L-1)氯吡格雷的培养液与EPCs共培养24h,检测黏附、迁移及增殖功能;应用含浓度为20×10-3 mmol·L-1氯吡格雷的培养液与EPCs共培养0.5~72.0 h,检测EPCs上述功能.结果 培养EPCs第4天,早期EPCs呈典型长梭形;培养EPCs第7天数目增多,可摄取Dil标记的乙酰化低密度脂蛋白以及FITC标记的荆豆凝集素.氯吡格雷可使细胞明显增多;不同浓度的氯吡格雷可改善其黏附(F=56.54,P=0.00)、迁移(F =60.23,P=0.00)和增殖(F=1.45,P=0.16)功能;氯吡格雷浓度为20×10-3 mmol·L-1时,保护作用最强;当共培养不同时间后,其仍可改善EPCs黏附(F=127.03,P =0.00)、迁移(F=96.03,P=0.00)和增殖(F=10.46,P=0.00)功能;保护作用呈时间依赖性,但于24h后达到平台期.结论 氯吡格雷可改善人外周血早期EPCs的黏附、迁移及增殖功能,且具有浓度依赖性和时间依赖性.%Objective To evaluate the effect of clopidogrel on the adherence,migration and proliferation of early endothelial progenitor cells(EPCs) from human peripheral blood. Methods Early EPCs were cultured and characterized. Then, EPCs were cultured for 24 hours with medium containing clopidogrel of different concentrations (1 ×10-3-200×10-3 mmol · L-1),and the adherence, migration and proliferation were tested; furthermore, the EPCs were cultured with medium containing 20 × 10-3 mmol · L-1 clopidogrel for different time(0.5 -72.0 h) ,and analysed the adherence,migration and proliferation again. Results The EPCs became long spindle on the 4th day,and these cells increased on the 7th day. Moreover,EPCs could take in Dil-acetylated low density lipoprotein( Dil-acLDL) and FTTC-ulex europaeus agglutinin ( FITC-UEA-I). Clopidogrel could significantly increase the number of cell; the

  5. SUPERNOVA REMNANT PROGENITOR MASSES IN M31

    Energy Technology Data Exchange (ETDEWEB)

    Jennings, Zachary G.; Williams, Benjamin F.; Dalcanton, Julianne J.; Gilbert, Karoline M.; Fouesneau, Morgan; Weisz, Daniel R. [Department of Astronomy, University of Washington Seattle, Box 351580, WA 98195 (United States); Murphy, Jeremiah W. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Dolphin, Andrew E., E-mail: zachjenn@uw.edu, E-mail: adolphin@raytheon.com [Raytheon, 1151 East Hermans Road, Tucson, AZ 85706 (United States)

    2012-12-10

    Using Hubble Space Telescope photometry, we age-date 59 supernova remnants (SNRs) in the spiral galaxy M31 and use these ages to estimate zero-age main-sequence masses (M{sub ZAMS}) for their progenitors. To accomplish this, we create color-magnitude diagrams (CMDs) and employ CMD fitting to measure the recent star formation history of the regions surrounding cataloged SNR sites. We identify any young coeval population that likely produced the progenitor star, then assign an age and uncertainty to that population. Application of stellar evolution models allows us to infer the M{sub ZAMS} from this age. Because our technique is not contingent on identification or precise location of the progenitor star, it can be applied to the location of any known SNRs. We identify significant young star formation around 53 of the 59 SNRs and assign progenitor masses to these, representing a factor of {approx}2 increase over currently measured progenitor masses. We consider the remaining six SNRs as either probable Type Ia candidates or the result of core-collapse progenitors that have escaped their birth sites. In general, the distribution of recovered progenitor masses is bottom-heavy, showing a paucity of the most massive stars. If we assume a single power-law distribution, dN/dM{proportional_to}M{sup {alpha}}, then we find a distribution that is steeper than a Salpeter initial mass function (IMF) ({alpha} = -2.35). In particular, we find values of {alpha} outside the range -2.7 {>=} {alpha} {>=} -4.4 to be inconsistent with our measured distribution at 95% confidence. If instead we assume a distribution that follows a Salpeter IMF up to some maximum mass, then we find that values of M{sub Max} > 26 are inconsistent with the measured distribution at 95% confidence. In either scenario, the data suggest that some fraction of massive stars may not explode. The result is preliminary and requires more SNRs and further analysis. In addition, we use our distribution to estimate a

  6. Impaired progenitor cell function in HIV-negative infants of HIV-positive mothers results in decreased thymic output and low CD4 counts

    DEFF Research Database (Denmark)

    Nielsen, S D; Jeppesen, D L; Kolte, L;

    2001-01-01

    Hematologic and immunologic functions were examined in 19 HIV-negative infants of HIV-positive mothers and 19 control infants of HIV-negative mothers. Control infants were selected to match for gestational age, weight, and mode of delivery. Cord blood was obtained from all infants and used for flow...... cytometric determination of lymphocyte subsets, including the naive CD4 count. Furthermore, to determine thymic output, cord blood mononuclear cells were used for determination of T-cell receptor excision circles (TRECs). Evaluation of progenitor cell function was done by means of colony-forming cell assay......). In combination with lower red blood cell counts in infants of HIV-positive mothers, this finding suggested impairment of progenitor cell function. Indeed, progenitors from infants of HIV-positive mothers had decreased cloning efficiency (15.7% +/- 2.6% vs 55.8% +/- 15.9%, P =.009) and seemed to generate fewer T...

  7. Blood transfusions

    Science.gov (United States)

    ... called homologous blood donation. Many communities have a blood bank at which any healthy person can donate blood. ... need to arrange with your hospital or local blood bank before your surgery to have directed donor blood. ...

  8. Origin of hemopoietic stromal progenitor cells in chimeras

    International Nuclear Information System (INIS)

    Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice

  9. Identification and purification of human erythroid progenitor cells by monoclonal antibody to the transferrin receptor (TU 67).

    Science.gov (United States)

    Herrmann, F; Griffin, J D; Sabbath, K D; Oster, W; Wernet, P; Mertelsmann, R

    1988-04-01

    Anti-TU 67 is a murine monoclonal antibody that recognizes the transferrin receptor. With respect to hematopoietic cells TU 67 is expressed by human multipotent colony-forming cells (CFU-Mix), erythroid progenitor cells (BFU-E and CFU-E) and a fraction of granulocyte/monocyte colony forming cells, but is not expressed by mature hematopoietic cells including erythrocytes, platelets, lymphocytes, and peripheral blood myeloid cells. The TU 67-positive fraction of normal bone marrow, separated by fluorescence-activated cell sorting (FACS) or immune rosettes, contained 87% of the erythroid progenitor cells. Erythroid progenitor cells were enriched up to 50-fold by using a combination of monoclonal antibodies to deplete mature hematopoietic cells, followed by positive selection of BFU-E and CFU-E by TU 67 antibody.

  10. Reverse-D-4F Increases the Number of Endothelial Progenitor Cells and Improves Endothelial Progenitor Cell Dysfunctions in High Fat Diet Mice.

    Science.gov (United States)

    Nana, Yang; Peng, Jiao; Jianlin, Zhang; Xiangjian, Zhang; Shutong, Yao; Enxin, Zhan; Bin, Li; Chuanlong, Zong; Hua, Tian; Yanhong, Si; Yunsai, Du; Shucun, Qin; Hui, Wang

    2015-01-01

    Although high density lipoprotein (HDL) improves the functions of endothelial progenitor cells (EPCs), the effect of HDL ApoAI mimetic peptide reverse-D-4F (Rev-D4F) on EPC mobilization and repair of EPC dysfunctions remains to be studied. In this study, we investigated the effects of Rev-D4F on peripheral blood cell subpopulations in C57 mice treated with a high fat diet and the mechanism of Rev-D4F in improving the function of EPCs impaired by tumor necrosis factor-α (TNF-α). The high fat diet significantly decreased the number of EPCs, EPC migratory functions, and the percentage of lymphocytes in the white blood cells. However, it significantly increased the number of white blood cells, the percentage of monocytes in the white blood cells, and the level of vascular endothelial growth factor (VEGF) and TNF-α in the plasma. Rev-D4F clearly inhibited the effect of the high fat diet on the quantification of peripheral blood cell subpopulations and cytokine levels, and increased stromal cell derived factor 1α (SDF-1α) in the plasma. We provided in vitro evidence that TNF-α impaired EPC proliferation, migration, and tube formation through inactive AKT and eNOS, which was restored by Rev-D4F treatment. In contrast, both the PI3-kinase (PI3K) inhibitor (LY294002) and AKT inhibitor (perifosine) obviously inhibited the restoration of Rev-4F on EPCs impaired by TNF-α. Our results suggested that Rev-D4F increases the quantity of endothelial progenitor cells through increasing the SDF-1α levels and decreasing the TNF-α level of peripheral blood in high fat diet-induced C57BL/6J mice, and restores TNF-α induced dysfunctions of EPCs partly through stimulating the PI3K/AKT signal pathway.

  11. Hypoxia inducible factor-2α regulates the development of retinal astrocytic network by maintaining adequate supply of astrocyte progenitors.

    Directory of Open Access Journals (Sweden)

    Li-Juan Duan

    Full Text Available Here we investigate the role of hypoxia inducible factor (HIF-2α in coordinating the development of retinal astrocytic and vascular networks. Three Cre mouse lines were used to disrupt floxed Hif-2α, including Rosa26(CreERT2, Tie2(Cre, and GFAP(Cre. Global Hif-2α disruption by Rosa26(CreERT2 led to reduced astrocytic and vascular development in neonatal retinas, whereas endothelial disruption by Tie2(Cre had no apparent effects. Hif-2α deletion in astrocyte progenitors by GFAP(Cre significantly interfered with the development of astrocytic networks, which failed to reach the retinal periphery and were incapable of supporting vascular development. Perplexingly, the abundance of strongly GFAP(+ mature astrocytes transiently increased at P0 before they began to lag behind the normal controls by P3. Pax2(+ and PDGFRα(+ astrocytic progenitors and immature astrocytes were dramatically diminished at all stages examined. Despite decreased number of astrocyte progenitors, their proliferation index or apoptosis was not altered. The above data can be reconciled by proposing that HIF-2α is required for maintaining the supply of astrocyte progenitors by slowing down their differentiation into non-proliferative mature astrocytes. HIF-2α deficiency in astrocyte progenitors may accelerate their differentiation into astrocytes, a change which greatly interferes with the replenishment of astrocyte progenitors due to insufficient time for proliferation. Rapidly declining progenitor supply may lead to premature cessation of astrocyte development. Given that HIF-2α protein undergoes oxygen dependent degradation, an interesting possibility is that retinal blood vessels may regulate astrocyte differentiation through their oxygen delivery function. While our findings support the consensus that retinal astrocytic template guides vascular development, they also raise the possibility that astrocytic and vascular networks may mutually regulate each other

  12. Culture materials affect ex vivo expansion of hematopoietic progenitor cells.

    Science.gov (United States)

    LaIuppa, J A; McAdams, T A; Papoutsakis, E T; Miller, W M

    1997-09-01

    Ex vivo expansion of hematopoietic cells is important for applications such as cancer treatment, gene therapy, and transfusion medicine. While cell culture systems are widely used to evaluate the biocompatibility of materials for implantation, the ability of materials to support proliferation of primary human cells in cultures for reinfusion into patients has not been addressed. We screened a variety of commercially available polymer (15 types), metal (four types), and glass substrates for their ability to support expansion of hematopoietic cells when cultured under conditions that would be encountered in a clinical setting. Cultures of peripheral blood (PB) CD34+ cells and mononuclear cells (MNC) were evaluated for expansion of total cells and colony-forming unit-granulocyte monocyte (CFU-GM; progenitors committed to the granulocyte and/or monocyte lineage). Human hematopoietic cultures in serum-free medium were found to be extremely sensitive to the substrate material. The only materials tested that supported expansion at or near the levels of polystyrene were tissue culture polystyrene, Teflon perfluoroalkoxy, Teflon fluorinated ethylene propylene, cellulose acetate, titanium, new polycarbonate, and new polymethylpentene. MNC were less sensitive to the substrate materials than the primitive CD34+ progenitors, although similar trends were seen for expansion of the two cell populations on the substrates tested. CFU-GM expansion was more sensitive to substrate materials than was total cell expansion. The detrimental effects of a number of the materials on hematopoietic cultures appear to be caused by protein adsorption and/or leaching of toxins. Factors such as cleaning, sterilization, and reuse significantly affected the performance of some materials as culture substrates. We also used PB CD34+ cell cultures to examine the biocompatibility of gas-permeable cell culture and blood storage bags and several types of tubing commonly used with biomedical equipment

  13. Change of endothelial progenitor cells in the bone marrow and peripheral blood of patients with acute leukemia and its clinical significance%急性白血病患者骨髓及外周血内皮祖细胞的变化及其临床意义

    Institute of Scientific and Technical Information of China (English)

    耿丛丛; 申政磊; 朱萍; 沈秀芬; 尹列芬; 杨玲

    2015-01-01

    Objectives To evaluate the count of endothelial progenitor cells (EPCs) in peripheral blood (PB) and bone marrow (BM) of acute leukemia (AL) patients and explore its clinical significance.Methods EPCs were detected by flow cytometry procedures in 43 AL patients and in 10 benign hematologic patients as control group.Results The absolute counts of EPCs in AL patients before the treatment [(119.46± 72.23)/μl in BM and (13.69±8.26)/pl in PB] were significantly higher than those in control group [(23.21 ± 12.59)/pl in BM and (1.86±1.18)/μl in PB] (P < 0.01).The absolute counts of EPCs were significandy higher in BM than those in BP in AL patients before the treatment (P < 0.001).After the treatment, the absolute counts of EPCs in no remission (NR) group [(110.02±67.28)/μl in BM and (10.04±9.51)/μ1 in PB] were significantly higher than those in control group (P < 0.05), while the counts of EPCs in complete remission (CR) group were no significant difference compared with those in control group (P > 0.05).After the treatment ,the absolute counts of EPCs both in BM and in BP of CR group [(26.32±17.44)/μl and (2.54±2.12)/μl, respectively] were significantly lower than those before treatment [(113.18±69.22)/μl and (14.45±10.76)/μl, respectively] (P < 0.05), however those of NR group were no significant difference than before (P > 0.05).The absolute counts of EPCs whether in PB or in BM were no significant difference between acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) (P > 0.05).The absolute counts of EPCs in PB of AL had a positive correlation with β2-MG and LDH (P < 0.05).Conclusions EPC levels are significantly increased in BM and BP of AL patients and may correlate with disease status, response to treatment and prognosis.%目的 探讨内皮祖细胞(EPC)在急性白血病(AL)患者骨髓及外周血中数量变化及其临床意义.方法 采用流式细胞术(FCM)对43例初治AL患者骨髓及外周血中的EPC进

  14. 间歇低氧合并肺气肿大鼠系统与内皮炎症状态及外周血内皮祖细胞水平研究%Systematic and Endothelial Inflammation Status and Endothelial Progenitor Cell Levels in Peripheral Blood in Intermittent Hypoxia and Emphysema Rat Model

    Institute of Scientific and Technical Information of China (English)

    王彦; 曹洁; 杨庆婵; 冯靖; 陈宝元

    2014-01-01

    目的:建立间歇低氧(IH)合并肺气肿重叠综合征(OS)大鼠模型,探讨OS大鼠系统及血管内皮炎症状态,并观察外周血内皮祖细胞(EPC)水平的变化。方法自制熏箱对大鼠进行16周的熏烟暴露造成大鼠肺气肿,从13周开始,在熏烟暴露同时,通过程控产生预制的间歇低氧/再氧合(IH/ROX)环境对大鼠进行IH暴露4周。60只雄性Wistar大鼠随机分为正常组(A组)、IH组(B组)、肺气肿组(C组)和OS组(D组),暴露结束后分别以ELISA法测定血浆及右颈总动脉内皮细胞中肿瘤坏死因子(TNF)-α、白介素(IL)-6水平,Real-time PCR法检测血管内皮细胞中RhoA mRNA含量,病理标本中测定颈动脉内中膜厚度(IMT)占全层厚度比值(C-IMT%),流式细胞仪测定循环血中EPC数量。结果 D组血浆和血管内皮细胞中TNF-α、IL-6水平以及血管内皮细胞中RhoA mRNA水平、C-IMT%均高于A、B、C组,而EPC数量均低于其他3组(均P<0.05)。结论 OS大鼠较单纯IH或单纯肺气肿大鼠系统及内皮损伤更加严重,且内皮修复能力更差,增加了心血管疾病风险。%Objective To establish the rat overlap syndrome (OS) model of intermittent hypoxia (IH) and emphyse-ma, explore the systematic and endothelial inflammation status, and observe the changes of endothelial progenitor cell (EPC) level in peripheral blood. Methods Sixty male Wistar rats were randomly divided into four groups:normal oxygen control group (A), IH group (B), emphysema group (C) and OS group (D). The rat model of emphysema was established by smoke ex-posure for 16 weeks. From the 13-week, pre-programmed intermittent hypoxia/re-oxygenation (IH/ROX) exposure was giv-en in the meantime of smoke exposure. After exposure, ELISA method was used to detect values of tumor necrosis factor al-pha (TNF-α) and interleukin (IL)-6 in plasma and in the endothelium of right common carotid artery

  15. Embryonic stem cell-derived neural progenitors transplanted to the hippocampus migrate on host vasculature

    Directory of Open Access Journals (Sweden)

    Chelsea M. Lassiter

    2016-05-01

    Full Text Available This study describes the migration of transplanted ESNPs either injected directly into the hippocampus of a mouse, seeded onto hippocampal slices, or under in vitro culture conditions. We show that transplanted mouse ESNPs associate with, and appear to migrate on the surface of the vasculature, and that human ESNPs also associate with blood vessels when seeded on hippocampal slices, and migrate towards BECs in vitro using a Boyden chamber assay. This initial adhesion to vessels is mediated, at least in part, via the integrin α6β1, as observed for SVZ neural progenitor cells. Our data are consistent with CXCL12, expressed by the astroglial-vasculature niche, playing an important role in the migration of transplanted neural progenitors within and outside of the hippocampus.

  16. Colonoscopy in the diagnosis of intestinal graft versus host disease and cytomegalovirus enteritis following allogeneic haematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    HE Jin-de; LIU Yu-lan; WANG Zhi-feng; LIU Dai-hong; CHEN Huan; CHEN Yu-hong

    2008-01-01

    Background Gastrointestinal graft versus host disease (GI-GVHD) and cytomegalovirus (CMV) enteritis are important complications following allogeneic haematopoietic stem cell transplantation (alIo-HSCT). We explored the role of colonoscopy in the diagnosis of GI-GVHD and CMV enteritis following alIo-HSCT to identify the endoscopic manifestations of GI-GVHD and CMV enteritis was made.Methods A retrospective analysis of the colonoscopic manifestations of GI-GVHD, CMV enteritis and GI-GVHD with concurrent CMV enteritis (GconC) and their related clinical issues.Results Forty-seven patients underwent 50 colonoscopies with diagnoses of 32 GI-GVHD, 7 CMV enteritis and 11 GconC. Both GI-GVHD and CMV enteritis had colonic mucosal lesions with various manifestations under colonoscopy. Tortoise shell like changes of the mucosa (12 of 32) and deep ulcers (2 of 7) were specific endoscopic manifestations for GI-GVHD and CMV enteritis, respectively, while mucosal oedema, erythema, congestion, erosion and shallow ulcers could not be used to differentiate GI-GVHD from CMV enteritis. GconC patients were prone to have oozing bleeding of the end ileal mucosa and typhlodicliditis. Of the biopsed specimens for GI-GVHD, CMV enteritis and GconC, 64%, 70% and 44% were taken from the rectum and sigmoid colon respectively.Conclusions Following alIo-HSCT, tortoise shell like changes and deep ulcers of the colonic mucosa are characteristic changes for Gl-GVHD and CMV enteritis, respectively, while the other lesions are not. Most of the GI-GVHDs and CMV enteritis cases can be diagnosed by left colon examination and tissue biopsy, but total colon examination to the terminal ileum is preferred.

  17. Informed consent--suggested procedures for informed consent for unrelated haematopoietic stem cell donors at various stages of recruitment, donor evaluation, and donor workup.

    Science.gov (United States)

    Rosenmayr, A; Hartwell, L; Egeland, T

    2003-04-01

    The Ethics Working Group of the World Marrow Donor Association (WMDA) was established to address the increasing and complex number of ethical issues surrounding unrelated haematopoietic stem cell donation where the selected donor and recipient reside in different countries. This paper considers the topic of informed donor consent, but recognises that the recommendations contained within the paper may be subject to cultural variances in interpretation, and to adjustment to meet the legal requirements of individual countries. Nevertheless, the extent of international cooperation establishes sufficient common denominators for the recommendations to be widely adhered to in the interests of best practice. PMID:12692618

  18. Challenge studies of European stocks of redfin perch, Perca fluviatilis L., and rainbow trout, Oncorhynchus mykiss (Walbaum), with epizootic haematopoietic necrosis virus

    DEFF Research Database (Denmark)

    Ariel, Ellen; Jensen, Ann Britt Bang

    2009-01-01

    A challenge model for comparison of the virulence of epizootic haematopoietic necrosis virus (EHNV) to European stock of redfin perch, Perca fluviatilis L., and rainbow trout, Oncorhynchus mykiss (Walbaum), was tested. The model investigated intraperitoneal (IP), bath and cohabitation routes at 10...... not significantly different from that recorded for 6 g fish challenged IP. No significant mortality was observed in any other treatment groups. Re-isolation of ranavirus was confirmed by IFAT and was con- sistently associated with dead or moribund fish in the trial groups challenged with EHNV. The...

  19. The endocannabinoid system drives neural progenitor proliferation.

    Science.gov (United States)

    Aguado, Tania; Monory, Krisztina; Palazuelos, Javier; Stella, Nephi; Cravatt, Benjamin; Lutz, Beat; Marsicano, Giovanni; Kokaia, Zaal; Guzmán, Manuel; Galve-Roperh, Ismael

    2005-10-01

    The discovery of multipotent neural progenitor (NP) cells has provided strong support for the existence of neurogenesis in the adult brain. However, the signals controlling NP proliferation remain elusive. Endocannabinoids, the endogenous counterparts of marijuana-derived cannabinoids, act as neuromodulators via presynaptic CB1 receptors and also control neural cell death and survival. Here we show that progenitor cells express a functional endocannabinoid system that actively regulates cell proliferation both in vitro and in vivo. Specifically, NPs produce endocannabinoids and express the CB1 receptor and the endocannabinoid-inactivating enzyme fatty acid amide hydrolase (FAAH). CB1 receptor activation promotes cell proliferation and neurosphere generation, an action that is abrogated in CB1-deficient NPs. Accordingly, proliferation of hippocampal NPs is increased in FAAH-deficient mice. Our results demonstrate that endocannabinoids constitute a new group of signaling cues that regulate NP proliferation and thus open novel therapeutic avenues for manipulation of NP cell fate in the adult brain.

  20. Interneuron progenitor transplantation to treat CNS dysfunction

    Directory of Open Access Journals (Sweden)

    Muhammad O Chohan

    2016-08-01

    Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

  1. Noninvasive Imaging of Administered Progenitor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Steven R Bergmann, M.D., Ph.D.

    2012-12-03

    The objective of this research grant was to develop an approach for labeling progenitor cells, specifically those that we had identified as being able to replace ischemic heart cells, so that the distribution could be followed non-invasively. In addition, the research was aimed at determining whether administration of progenitor cells resulted in improved myocardial perfusion and function. The efficiency and toxicity of radiolabeling of progenitor cells was to be evaluated. For the proposed clinical protocol, subjects with end-stage ischemic coronary artery disease were to undergo a screening cardiac positron emission tomography (PET) scan using N-13 ammonia to delineate myocardial perfusion and function. If they qualified based on their PET scan, they would undergo an in-hospital protocol whereby CD34+ cells were stimulated by the administration of granulocytes-colony stimulating factor (G-CSF). CD34+ cells would then be isolated by apharesis, and labeled with indium-111 oxine. Cells were to be re-infused and subjects were to undergo single photon emission computed tomography (SPECT) scanning to evaluate uptake and distribution of labeled progenitor cells. Three months after administration of progenitor cells, a cardiac PET scan was to be repeated to evaluate changes in myocardial perfusion and/or function. Indium oxine is a radiopharmaceutical for labeling of autologous lymphocytes. Indium-111 (In-111) decays by electron capture with a t{sub ½} of 67.2 hours (2.8 days). Indium forms a saturated complex that is neutral, lipid soluble, and permeates the cell membrane. Within the cell, the indium-oxyquinolone complex labels via indium intracellular chelation. Following leukocyte labeling, ~77% of the In-111 is incorporated in the cell pellet. The presence of red cells and /or plasma reduces the labeling efficacy. Therefore, the product needed to be washed to eliminate plasma proteins. This repeated washing can damage cells. The CD34 selected product was a 90

  2. Growth factor-activated stem cell circuits and stromal signals cooperatively accelerate non-integrated iPSC reprogramming of human myeloid progenitors.

    Directory of Open Access Journals (Sweden)

    Tea Soon Park

    Full Text Available Nonviral conversion of skin or blood cells into clinically useful human induced pluripotent stem cells (hiPSC occurs in only rare fractions (~0.001%-0.5% of donor cells transfected with non-integrating reprogramming factors. Pluripotency induction of developmentally immature stem-progenitors is generally more efficient than differentiated somatic cell targets. However, the nature of augmented progenitor reprogramming remains obscure, and its potential has not been fully explored for improving the extremely slow pace of non-integrated reprogramming. Here, we report highly optimized four-factor reprogramming of lineage-committed cord blood (CB myeloid progenitors with bulk efficiencies of ~50% in purified episome-expressing cells. Lineage-committed CD33(+CD45(+CD34(- myeloid cells and not primitive hematopoietic stem-progenitors were the main targets of a rapid and nearly complete non-integrated reprogramming. The efficient conversion of mature myeloid populations into NANOG(+TRA-1-81(+ hiPSC was mediated by synergies between hematopoietic growth factor (GF, stromal activation signals, and episomal Yamanaka factor expression. Using a modular bioinformatics approach, we demonstrated that efficient myeloid reprogramming correlated not to increased proliferation or endogenous Core factor expressions, but to poised expression of GF-activated transcriptional circuits that commonly regulate plasticity in both hematopoietic progenitors and embryonic stem cells (ESC. Factor-driven conversion of myeloid progenitors to a high-fidelity pluripotent state was further accelerated by soluble and contact-dependent stromal signals that included an implied and unexpected role for Toll receptor-NFκB signaling. These data provide a paradigm for understanding the augmented reprogramming capacity of somatic progenitors, and reveal that efficient induced pluripotency in other cell types may also require extrinsic activation of a molecular framework that commonly

  3. BMP signaling in the nephron progenitor niche

    OpenAIRE

    Oxburgh, Leif; Brown, Aaron C.; Fetting, Jennifer; Hill, Beth

    2011-01-01

    Bone morphogenic proteins (BMPs) play diverse roles in embryonic kidney development, regulating essential aspects of both ureteric bud and nephron development. In this review, we provide an overview of reported expression patterns and functions of BMP signaling components within the nephrogenic zone or nephron progenitor niche of the developing kidney. Reported in situ hybridization results are relatively challenging to interpret and sometimes conflicting. Comparing these with high-resolution...

  4. Human Fetal Progenitor Tenocytes for Regenerative Medicine.

    OpenAIRE

    Grognuz A.; Scaletta C.; Farron A.; Raffoul W.; Applegate L.A.

    2016-01-01

    Tendon injuries are very frequent and affect a wide and heterogeneous population. Unfortunately, the healing process is long with outcomes that are not often satisfactory due to fibrotic tissue appearance, which leads to scar and adhesion development. Tissue engineering and cell therapies emerge as interesting alternatives to classical treatments. In this study, we evaluated human fetal progenitor tenocytes (hFPTs) as a potential cell source for treatment of tendon afflictions, as fetal cells...

  5. TOX3 regulates neural progenitor identity.

    Science.gov (United States)

    Sahu, Sanjeeb Kumar; Fritz, Alina; Tiwari, Neha; Kovacs, Zsuzsa; Pouya, Alireza; Wüllner, Verena; Bora, Pablo; Schacht, Teresa; Baumgart, Jan; Peron, Sophie; Berninger, Benedikt; Tiwari, Vijay K; Methner, Axel

    2016-07-01

    The human genomic locus for the transcription factor TOX3 has been implicated in susceptibility to restless legs syndrome and breast cancer in genome-wide association studies, but the physiological role of TOX3 remains largely unknown. We found Tox3 to be predominantly expressed in the developing mouse brain with a peak at embryonic day E14 where it co-localizes with the neural stem and progenitor markers Nestin and Sox2 in radial glia of the ventricular zone and intermediate progenitors of the subventricular zone. Tox3 is also expressed in neural progenitor cells obtained from the ganglionic eminence of E15 mice that express Nestin, and it specifically binds the Nestin promoter in chromatin immunoprecipitation assays. In line with this, over-expression of Tox3 increased Nestin promoter activity, which was cooperatively enhanced by treatment with the stem cell self-renewal promoting Notch ligand Jagged and repressed by pharmacological inhibition of Notch signaling. Knockdown of Tox3 in the subventricular zone of E12.5 mouse embryos by in utero electroporation of Tox3 shRNA revealed a reduced Nestin expression and decreased proliferation at E14 and a reduced migration to the cortical plate in E16 embryos in electroporated cells. Together, these results argue for a role of Tox3 in the development of the nervous system. PMID:27080130

  6. Endothelial progenitor cells in hematologic malignancies.

    Science.gov (United States)

    Testa, Ugo; Saulle, Ernestina; Castelli, Germana; Pelosi, Elvira

    2016-01-01

    Studies carried out in the last years have improved the understanding of the cellular and molecular mechanisms controlling angiogenesis during adult life in normal and pathological conditions. Some of these studies have led to the identification of some progenitor cells that sustain angiogenesis through indirect, paracrine mechanisms (hematopoietic angiogenic cells) and through direct mechanisms, i.e., through their capacity to generate a progeny of phenotypically and functionally competent endothelial cells [endothelial colony forming cells (ECFCs)]. The contribution of these progenitors to angiogenetic processes under physiological and pathological conditions is intensively investigated. Angiogenetic mechanisms are stimulated in various hematological malignancies, including chronic myeloid leukemia (CML), acute myeloid leukemia (AML), myelodysplastic syndromes and multiple myeloma, resulting in an increased angiogenesis that contributes to disease progression. In some of these conditions there is preliminary evidence that some endothelial cells could derive from the malignant clone, thus leading to the speculation that the leukemic cell derives from the malignant transformation of a hemangioblastic progenitor, i.e., of a cell capable of differentiation to the hematopoietic and to the endothelial cell lineages. Our understanding of the mechanisms underlying increased angiogenesis in these malignancies not only contributed to a better knowledge of the mechanisms responsible for tumor progression, but also offered the way for the discovery of new therapeutic targets. PMID:27583252

  7. To stay or to leave: Stem cells and progenitor cells navigating the S1P gradient

    Institute of Scientific and Technical Information of China (English)

    Andrew; Hsu; Jen-Fu; Lee; Daniel; E; Cramer; Menq-Jer; Lee

    2011-01-01

    Most hematopoietic stem progenitor cells (HSPCs) reside in bone marrow (BM), but a small amount of HSPCs have been found to circulate between BM and tissues through blood and lymph. Several lines of evidence suggest that sphingosine-1-phosphate (S1P) gradient triggers HSPC egression to blood circulation after mobilization from BM stem cell niches. Stem cells also visit certain tissues. After a temporary 36 h short stay in local tissues, HSPCs go to lymph in response to S1P gradient between lymph and tissue and eventually enter the blood circulation. S1P also has a role in the guidance of the primitive HSPCs homing to BM in vivo, as S1P analogue FTY720 treatment can improve HSPC BM homing and engraftment. In stress conditions, various stem cells or progenitor cells can be attracted to local injured tissues and participate in local tissue cell differentiation and tissue rebuilding through modulation the expression level of S1P1, S1P2 or S1P3 receptors. Hence, S1P is important for stem cells circulation in blood system to accomplish its role in body surveillance and injury recovery.

  8. Awareness, Knowledge, and Acceptance of Haematopoietic Stem Cell Transplantation for Sickle Cell Anaemia in Nigeria

    Science.gov (United States)

    Kagu, Modu Baba; Wakama, Tamunomieibi; Babadoko, Aliyu Ahmadu; Damulak, Dapus Obadiah; Ocheni, Sunday; Asuquo, Marcus Inyama

    2016-01-01

    Background. Sickle cell anaemia (SCA) is an inherited condition whose clinical manifestations arise from the tendency of haemoglobin to polymerize and deform red blood cells into characteristic sickle shape. Allogeneic bone marrow transplantation offers a cure. The aim of this study was to determine the level of awareness, knowledge, and acceptance of this beneficial procedure in Nigeria. Materials and Methods. This multicentre cross-sectional study was conducted in 7 tertiary hospitals in Nigeria in 2015. Approval was obtained from each institution's research and ethics committee. A pretested structured questionnaire was administered to respondents aged 18 years and above and to the parents or guardians of those below 18 years of age. Results. There were 265 respondents comprising 120 males and 145 females. One hundred and seventy-one (64.5%) respondents were aware of BMT for the treatment of SCA. About 67.8% (116 of 171) of those who were aware believed SCA can be cured with BMT (p = 0.001) and 49.7% (85 of 171) of the respondents accepted BMT (p = 0.001). Conclusion. Awareness of BMT in Nigeria is low when compared with reports from developed countries. The knowledge is poor and acceptance is low. With adequate information, improved education, and psychological support, more Nigerians will embrace BMT.

  9. Awareness, Knowledge, and Acceptance of Haematopoietic Stem Cell Transplantation for Sickle Cell Anaemia in Nigeria

    Directory of Open Access Journals (Sweden)

    Adewumi Adediran

    2016-01-01

    Full Text Available Background. Sickle cell anaemia (SCA is an inherited condition whose clinical manifestations arise from the tendency of haemoglobin to polymerize and deform red blood cells into characteristic sickle shape. Allogeneic bone marrow transplantation offers a cure. The aim of this study was to determine the level of awareness, knowledge, and acceptance of this beneficial procedure in Nigeria. Materials and Methods. This multicentre cross-sectional study was conducted in 7 tertiary hospitals in Nigeria in 2015. Approval was obtained from each institution’s research and ethics committee. A pretested structured questionnaire was administered to respondents aged 18 years and above and to the parents or guardians of those below 18 years of age. Results. There were 265 respondents comprising 120 males and 145 females. One hundred and seventy-one (64.5% respondents were aware of BMT for the treatment of SCA. About 67.8% (116 of 171 of those who were aware believed SCA can be cured with BMT (p=0.001 and 49.7% (85 of 171 of the respondents accepted BMT (p=0.001. Conclusion. Awareness of BMT in Nigeria is low when compared with reports from developed countries. The knowledge is poor and acceptance is low. With adequate information, improved education, and psychological support, more Nigerians will embrace BMT.

  10. Blood culture

    Science.gov (United States)

    Culture - blood ... A blood sample is needed . The site where blood will be drawn is first cleaned with an antiseptic such ... organism from the skin getting into (contaminating) the blood sample and causing a false-positive result (see ...

  11. Blood Thinners

    Science.gov (United States)

    If you have some kinds of heart or blood vessel disease, or if you have poor blood flow to your brain, your doctor may recommend that you take a blood thinner. Blood thinners reduce the risk of heart ...

  12. Blood Basics

    Science.gov (United States)

    ... Patient Group Links Advocacy Toolkit Home For Patients Blood Basics Blood is a specialized body fluid. It ... about 9 pints. Jump To: The Components of Blood and Their Importance Many people have undergone blood ...

  13. Blood pressure

    Science.gov (United States)

    ... the walls of the arteries is called blood pressure. Blood pressure is measured both as the heart contracts, which ... as it relaxes, which is called diastole. Normal blood pressure is considered to be a systolic blood pressure ...

  14. Cryopreservation of hematopoietic stem/progenitor cells for therapeutic use.

    Science.gov (United States)

    Watt, Suzanne M; Austin, Eric; Armitage, Sue

    2007-01-01

    To date, more than 25,000 hematopoietic transplants have been carried out across Europe for hematological disorders, the majority being for hematological malignancies. At least 70% of these are autologous transplants, the remaining 30% being allogeneic, which are sourced from related (70% of the allogeneic) or unrelated donors. Peripheral blood mobilized with granulocyte colony stimulating factor is the major source of stem cells for transplantation, being used in approx 95% of autologous transplants and in approx 65% of allogeneic transplants. Other cell sources used for transplantation are bone marrow and umbilical cord blood. One crucial advance in the treatment of these disorders has been the development of the ability to cryopreserve hematopoietic stem cells for future transplantation. For bone marrow and mobilized peripheral blood, the majority of cryopreserved harvests come from autologous collections that are stored prior to a planned infusion following further treatment of the patient or at the time of a subsequent relapse. Other autologous harvests are stored as backup or "rainy day" harvests, the former specifically being intended to rescue patients who develop graft failure following an allogeneic transplant or who may require this transplant at a later date. Allogeneic bone marrow and mobilized peripheral blood are less often cryopreserved than autologous harvests. This is in contrast to umbilical cord blood that may be banked for directed or sibling (related) hematopoietic stem cell transplants, for allogeneic unrelated donations, and for autologous donations. Allogeneic unrelated donations are of particular use for providing a source of hematopoietic stem cells for ethnic minorities, patients with rare human leukocyte antigen types, or where the patient urgently requires a transplant and cannot wait for the weeks to months required to prepare a bone marrow donor. There are currently more than 200,000 banked umbilical cord blood units registered with

  15. Experiment list: SRX1293142 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available enitor cells from which all blood cells derive. 26518451,99.5,17.8,41091 GSM1897161: Sensitive line H3K27ac ...ChIP; Mus musculus; ChIP-Seq source_name=Sensitive line || tissue=haematopoietic progenitors || condition=Sensitive

  16. PPAR-α and glucocorticoid receptor synergize to promote erythroid progenitor self-renewal.

    Science.gov (United States)

    Lee, Hsiang-Ying; Gao, Xiaofei; Barrasa, M Inmaculada; Li, Hu; Elmes, Russell R; Peters, Luanne L; Lodish, Harvey F

    2015-06-25

    Many acute and chronic anaemias, including haemolysis, sepsis and genetic bone marrow failure diseases such as Diamond-Blackfan anaemia, are not treatable with erythropoietin (Epo), because the colony-forming unit erythroid progenitors (CFU-Es) that respond to Epo are either too few in number or are not sensitive enough to Epo to maintain sufficient red blood cell production. Treatment of these anaemias requires a drug that acts at an earlier stage of red cell formation and enhances the formation of Epo-sensitive CFU-E progenitors. Recently, we showed that glucocorticoids specifically stimulate self-renewal of an early erythroid progenitor, burst-forming unit erythroid (BFU-E), and increase the production of terminally differentiated erythroid cells. Here we show that activation of the peroxisome proliferator-activated receptor α (PPAR-α) by the PPAR-α agonists GW7647 and fenofibrate synergizes with the glucocorticoid receptor (GR) to promote BFU-E self-renewal. Over time these agonists greatly increase production of mature red blood cells in cultures of both mouse fetal liver BFU-Es and mobilized human adult CD34(+) peripheral blood progenitors, with a new and effective culture system being used for the human cells that generates normal enucleated reticulocytes. Although Ppara(-/-) mice show no haematological difference from wild-type mice in both normal and phenylhydrazine (PHZ)-induced stress erythropoiesis, PPAR-α agonists facilitate recovery of wild-type but not Ppara(-/-) mice from PHZ-induced acute haemolytic anaemia. We also show that PPAR-α alleviates anaemia in a mouse model of chronic anaemia. Finally, both in control and corticosteroid-treated BFU-E cells, PPAR-α co-occupies many chromatin sites with GR; when activated by PPAR-α agonists, additional PPAR-α is recruited to GR-adjacent sites and presumably facilitates GR-dependent BFU-E self-renewal. Our discovery of the role of PPAR-α agonists in stimulating self-renewal of early erythroid

  17. PPARα and glucocorticoid receptor synergize to promote erythroid progenitor self-renewal

    Science.gov (United States)

    Lee, Hsiang-Ying; Gao, Xiaofei; Barrasa, M. Inmaculada; Li, Hu; Elmes, Russell R.; Peters, Luanne L.; Lodish, Harvey F.

    2015-01-01

    Summary Many acute and chronic anemias, including hemolysis, sepsis, and genetic bone marrow failure diseases such as Diamond-Blackfan Anemia (DBA), are not treatable with erythropoietin (Epo), because the colony-forming unit erythroid progenitors (CFU-Es) that respond to Epo are either too few in number or are not sensitive enough to Epo to maintain sufficient red blood cell production 1,2,3–5,6,7,8,9. Treatment of these anemias requires a drug that acts at an earlier stage of red cell formation and enhances the formation of Epo-sensitive CFU-E progenitors. Recently we showed that glucocorticoids specifically stimulate self-renewal of the early erythroid progenitor, the burst-forming unit erythroid (BFU-E), and increase the production of terminally differentiated erythroid cells 10,11. Here we demonstrate that activation of the peroxisome proliferator-activated receptor alpha (PPARα) by PPARα agonists, GW7647 and fenofibrate, synergizes with glucocorticoid receptor (GR) to promote BFU-E self-renewal. Over time these agonists greatly increase production of mature red blood cells in cultures both of mouse fetal liver BFU-Es and of mobilized human adult CD34+ peripheral blood progenitors, the latter employing a new and effective culture system that generates normal enucleated reticulocytes. While PPARα−/− mice show no hematological difference from wild-type mice in both normal and phenylhydrazine (PHZ)-induced stress erythropoiesis, PPARα agonists facilitate recovery of wild-type mice, but not PPARα−/− mice, from PHZ-induced acute hemolytic anemia. We also showed that PPARα alleviates anemia in a mouse model of chronic anemia. Finally, both in control and corticosteroid-treated BFU-E cells PPARα co-occupies many chromatin sites with GR; when activated by PPARα agonists, additional PPARα is recruited to GR-adjacent sites and presumably facilitates GR-dependent BFU-E self-renewal. Our discovery of the role of PPARα agonists in stimulating self

  18. Asymmetric centrosome inheritance maintains neural progenitors in neocortex

    OpenAIRE

    Wang, Xiaoqun; Tsai, Jin-Wu; Imai, Janice H.; Lian, Wei-Nan; Vallee, Richard B.; Shi, Song-Hai

    2009-01-01

    Asymmetric divisions of radial glial progenitors produce self-renewing radial glia and differentiating cells simultaneously in the ventricular zone (VZ) of the developing neocortex. While differentiating cells leave the VZ to constitute the future neocortex, renewing radial glial progenitors stay in the VZ for subsequent divisions. The differential behaviour of progenitors and their differentiating progeny is essential for neocortical development; however, the mechanisms that ensure these beh...

  19. Distribution and expression analysis of transcription factors in tissues and progenitor cell populations of the goldfish (Carassius auratus L.) in response to growth factors and pathogens.

    Science.gov (United States)

    Katzenback, Barbara A; Karpman, Matthew; Belosevic, Miodrag

    2011-05-01

    We report on the mRNA levels of a panel of transcription factors in the kidney and spleen tissues, and in the cell populations from the blood, the spleen, and in the sorted kidney progenitor cells. The mRNA levels of cebpα, cjun, cmyb, egr1, gata1, gata2, gata3, lmo2, mafb, pax5, pu.1 and runx1 were assessed in healthy goldfish as well as in fish challenged with two different pathogens, Aeromonas salmonicida A449 or Trypanosoma carassii. Spleen tissue from healthy goldfish showed higher expression of myeloid (cjun), erythroid (gata1) and lymphoid (gata3, pax5) transcription factors, and lower expression of the myeloid transcription factor cebpα when compared to that of kidney. Splenocytes and PBLs had significantly higher mRNA levels of the transcription factors involved in myeloid (pu.1, mafb, cjun, egr1, cebpa), erythroid (gata1, lmo2), and lymphoid pathways (gata3 and pax5) compared to sorted kidney R1 progenitor cells, while R1 progenitor cells had higher mRNA levels of early progenitor transcription factors (runx1 and cmyb). Furthermore, the R1 progenitor cells had higher mRNA levels of the transcription factors involved in early progenitor cells (egr1, gata2) and the lymphoid lineage progenitors (gata3, pax5) compared to those in kidney. The mRNA levels of the transcription factors (gata2, mafb, cjun, gata1, lmo2, gata3, and pax5) in R1 progenitor cells changed during cultivation; they were elevated in day 2 R1 cells and down-regulated by day 6 of cultivation, when compared to those of day 0 R1 cells. Treatment of day 2 R1 progenitor cells with rgCSF-1 resulted in an up-regulation of transcription factors important for myeloid cell development (cjun and egr1). Similarly, rgkitla up-regulated the expressions of myeloid (mafb, egr1 and cebpa) transcription factors. Changes in the expression of transcription factors in the R1 progenitor cells were related to the observed developmental processes of myeloid progenitor cells during cultivation or treatment with

  20. The haematopoietic GTPase RhoH modulates IL3 signalling through regulation of STAT activity and IL3 receptor expression

    Directory of Open Access Journals (Sweden)

    Gündogdu Mehtap S

    2010-08-01

    Full Text Available Abstract Background RhoH is a constitutively active member of the family of Rho GTPases. Its expression is restricted to the haematopoietic lineage, where it serves as a positive regulator for T cell selection and mast cell function and as a negative regulator for growth-related functions in other lineages. Here, we examined the activation of signal transducer and activator of transcription (STAT proteins in response to stimulation with interleukin 3 (IL3. Results Using the murine IL3-dependent cell line BaF3 we investigated the influence of RhoH protein expression levels on IL3-mediated cellular responses. RhoH overexpressing cells showed lower sensitivity to IL3 and decreased STAT5 activation. SiRNA-mediated repression of RhoH gene expression led to an increase in proliferation and STAT5 activity which correlated with an increased number of IL3 receptor α chain molecules, also known as CD123, expressed at the cell surface. Interestingly, these findings could be reproduced using human THP-1 cells as a model system for acute myeloid leukaemia, where low RhoH levels are known to be an unfavourable prognostic marker. Overexpression of RhoH on the other hand caused an induction of STAT1 activity and western blot analysis revealed that activated STAT1 is phosphorylated on Tyr701. STAT1 is known to induce apoptosis or cell cycle arrest and we detected an upregulation of cyclin-dependent kinase inhibitors (CDKI p21Cip1 and p27Kip1 in RhoH overexpressing BaF3 cells. Conclusions We propose that RhoH functions as a negative regulator for IL3-induced signals through modulation of the JAK-STAT pathway. High levels of RhoH allow the IL3-dependent activation of STAT1 causing decreased proliferation through upregulation of p21Cip1 and p27Kip1. Low RhoH levels on the other hand led to an upregulation of IL3-dependent cell growth, STAT5 activity and an increase of CD123 surface expression, linking RhoH to a CD123/STAT5 phenotype that has been described in AML

  1. Bone Marrow Stress Decreases Osteogenic Progenitors.

    Science.gov (United States)

    Ng, Adeline H; Baht, Gurpreet S; Alman, Benjamin A; Grynpas, Marc D

    2015-11-01

    Age-related bone loss may be a result of declining levels of stem cells in the bone marrow. Using the Col2.3Δtk (DTK) transgenic mouse, osteoblast depletion was used as a source of marrow stress in order to investigate the effects of aging on osteogenic progenitors which reside in the marrow space. Five-month-old DTK mice were treated with one or two cycles of ganciclovir to conditionally ablate differentiated osteoblasts, whereas controls were saline-treated. Treatment cycles were two weeks in length followed by four weeks of recovery. All animals were sacrificed at 8 months of age; bone marrow stromal cells (BMSCs) were harvested for cell culture and whole bones were excised for bone quality assessment. Colony-forming unit (CFU) assays were conducted to investigate the osteogenic potential of BMSC in vitro, and RNA was extracted to assess the expression of osteoblastic genes. Bone quality assessments included bone histomorphometry, TRAP staining, microcomputed tomography, and biomechanical testing. Osteoblast depletion decreased CFU-F (fibroblast), CFU-ALP (alkaline phosphatase), and CFU-VK (von Kossa) counts and BMSC osteogenic capacity in cell culture. Ex vivo, there were no differences in bone mineral density of vertebrae or femurs between treatment groups. Histology showed a decrease in bone volume and bone connectivity with repeated osteoblast depletion; however, this was accompanied by an increase in bone formation rate. There were no notable differences in osteoclast parameters or observed bone marrow adiposity. We have developed a model that uses bone marrow stress to mimic age-related decrease in osteogenic progenitors. Our data suggest that the number of healthy BMSCs and their osteogenic potential decline with repeated osteoblast depletion. However, activity of the remaining osteoblasts increases to compensate for this loss in progenitor osteogenic potential. PMID:26220824

  2. Enhancing endothelial progenitor cell for clinical use

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Circulating endothelial progenitor cells (EPCs) havebeen demonstrated to correlate negatively with vascularendothelial dysfunction and cardiovascular risk factors.However, translation of basic research into the clinicalpractice has been limited by the lack of unambiguousand consistent definitions of EPCs and reduced EPCcell number and function in subjects requiring them forclinical use. This article critically reviews the definitionof EPCs based on commonly used protocols, their valueas a biomarker of cardiovascular risk factor in subjectswith cardiovascular disease, and strategies to enhanceEPCs for treatment of ischemic diseases.

  3. Apoptotic neurons induce proliferative responses of progenitor cells in the postnatal neocortex.

    Science.gov (United States)

    Petrenko, Volodymyr; Mihhailova, Jevgenia; Salmon, Patrick; Kiss, Jozsef Z

    2015-11-01

    Apoptotic cell death is the leading cause of neuronal loss after neonatal brain injury. Little is known about the intrinsic capacity of the immature cerebral cortex for replacing dead cells. Here we test the hypothesis that neuronal apoptosis is able to trigger compensatory proliferation in surrounding cells. In order to establish a "pure" apoptotic cell death model and to avoid the confounding effects of broken blood-brain barrier and inflammatory reactions, we used a diphtheria toxin (DT) and diphtheria toxin receptor (DTR) system to induce ablation of layer IV neurons in the rodent somatosensory cortex during the early postnatal period. We found that DT-triggered apoptosis is a slowly progressing event lasting about for 7 days. While dying cells expressed the morphological features of apoptosis, we could not detect immunoreactivity for activated caspase-3 in these cells. Microglia activation and proliferation represented the earliest cellular responses to apoptotic cell death. In addition, we found that induced apoptosis triggered a massive proliferation of undifferentiated progenitor cell pool including Sox2 as well as NG2 cells. The default differentiation pattern of proliferating progenitors appears to be the glial phenotype; we could not find evidence for newly generated neurons in response to apoptotic neuronal death. These results suggest that mitotically active progenitor populations are intrinsically capable to contribute to the repair process of injured cortical tissue and may represent a potential target for neuronal replacement strategies.

  4. Human-derived neural progenitors functionally replace astrocytes in adult mice

    Science.gov (United States)

    Chen, Hong; Qian, Kun; Chen, Wei; Hu, Baoyang; Blackbourn, Lisle W.; Du, Zhongwei; Ma, Lixiang; Liu, Huisheng; Knobel, Karla M.; Ayala, Melvin; Zhang, Su-Chun

    2015-01-01

    Astrocytes are integral components of the homeostatic neural network as well as active participants in pathogenesis of and recovery from nearly all neurological conditions. Evolutionarily, compared with lower vertebrates and nonhuman primates, humans have an increased astrocyte-to-neuron ratio; however, a lack of effective models has hindered the study of the complex roles of human astrocytes in intact adult animals. Here, we demonstrated that after transplantation into the cervical spinal cords of adult mice with severe combined immunodeficiency (SCID), human pluripotent stem cell–derived (PSC-derived) neural progenitors migrate a long distance and differentiate to astrocytes that nearly replace their mouse counterparts over a 9-month period. The human PSC-derived astrocytes formed networks through their processes, encircled endogenous neurons, and extended end feet that wrapped around blood vessels without altering locomotion behaviors, suggesting structural, and potentially functional, integration into the adult mouse spinal cord. Furthermore, in SCID mice transplanted with neural progenitors derived from induced PSCs from patients with ALS, astrocytes were generated and distributed to a similar degree as that seen in mice transplanted with healthy progenitors; however, these mice exhibited motor deficit, highlighting functional integration of the human-derived astrocytes. Together, these results indicate that this chimeric animal model has potential for further investigating the roles of human astrocytes in disease pathogenesis and repair. PMID:25642771

  5. Human progenitor cell recruitment via SDF-1α coacervate-laden PGS vascular grafts.

    Science.gov (United States)

    Lee, Kee-Won; Johnson, Noah R; Gao, Jin; Wang, Yadong

    2013-12-01

    Host cell recruitment is crucial for vascular graft remodeling and integration into the native blood vessel; it is especially important for cell-free strategies which rely on host remodeling. Controlled release of growth factors from vascular grafts may enhance host cell recruitment. Stromal cell-derived factor (SDF)-1α has been shown to induce host progenitor cell migration and recruitment; however, its potential in regenerative therapies is often limited due to its short half-life in vivo. This report describes a coacervate drug delivery system for enhancing progenitor cell recruitment into an elastomeric vascular graft by conferring protection of SDF-1α. Heparin and a synthetic polycation are used to form a coacervate, which is incorporated into poly(glycerol sebacate) (PGS) scaffolds. In addition to protecting SDF-1α, the coacervate facilitates uniform scaffold coating. Coacervate-laden scaffolds have high SDF-1α loading efficiency and provide sustained release under static and physiologically-relevant flow conditions with minimal initial burst release. In vitro assays showed that coacervate-laden scaffolds enhance migration and infiltration of human endothelial and mesenchymal progenitor cells by maintaining a stable SDF-1α gradient. These results suggest that SDF-1α coacervate-laden scaffolds show great promise for in situ vascular regeneration.

  6. Regulatory Systems in Bone Marrow for Hematopoietic Stem/Progenitor Cells Mobilization and Homing

    Directory of Open Access Journals (Sweden)

    P. Alvarez

    2013-01-01

    Full Text Available Regulation of hematopoietic stem cell release, migration, and homing from the bone marrow (BM and of the mobilization pathway involves a complex interaction among adhesion molecules, cytokines, proteolytic enzymes, stromal cells, and hematopoietic cells. The identification of new mechanisms that regulate the trafficking of hematopoietic stem/progenitor cells (HSPCs cells has important implications, not only for hematopoietic transplantation but also for cell therapies in regenerative medicine for patients with acute myocardial infarction, spinal cord injury, and stroke, among others. This paper reviews the regulation mechanisms underlying the homing and mobilization of BM hematopoietic stem/progenitor cells, investigating the following issues: (a the role of different factors, such as stromal cell derived factor-1 (SDF-1, granulocyte colony-stimulating factor (G-CSF, and vascular cell adhesion molecule-1 (VCAM-1, among other ligands; (b the stem cell count in peripheral blood and BM and influential factors; (c the therapeutic utilization of this phenomenon in lesions in different tissues, examining the agents involved in HSPCs mobilization, such as the different forms of G-CSF, plerixafor, and natalizumab; and (d the effects of this mobilization on BM-derived stem/progenitor cells in clinical trials of patients with different diseases.

  7. Cord blood banking - bio-objects on the borderlands between community and immunity.

    Science.gov (United States)

    Brown, Nik; Williams, Rosalind

    2015-01-01

    Umbilical cord blood (UCB) has become the focus of intense efforts to collect, screen and bank haematopoietic stem cells (HSCs) in hundreds of repositories around the world. UCB banking has developed through a broad spectrum of overlapping banking practices, sectors and institutional forms. Superficially at least, these sectors have been widely distinguished in bioethical and policy literature between notions of the 'public' and the 'private', the commons and the market respectively. Our purpose in this paper is to reflect more critically on these distinctions and to articulate the complex practical and hybrid nature of cord blood as a 'bio-object' that straddles binary conceptions of the blood economies. The paper draws upon Roberto Esposito's reflections on biopolitics and his attempt to transcend the dualistic polarisations of immunity and community, or the private and the public. We suggest that his thoughts on immunitary hospitality resonate with many of the actual features and realpolitik of a necessarily internationalised and globally distributed UCB 'immunitary regime'.

  8. Heat shock factor 1 contributes to ischemia-induced angiogenesis by regulating the mobilization and recruitment of bone marrow stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Masayuki Kubo

    Full Text Available Bone marrow (BM-derived stem/progenitor cells play an important role in ischemia-induced angiogenesis in cardiovascular diseases. Heat shock factor 1 (HSF1 is known to be induced in response to hypoxia and ischemia. We examined whether HSF1 contributes to ischemia-induced angiogenesis through the mobilization and recruitment of BM-derived stem/progenitor cells using HSF1-knockout (KO mice. After the induction of ischemia, blood flow and microvessel density in the ischemic hindlimb were significantly lower in the HSF1-KO mice than in the wild-type (WT mice. The mobilization of BM-derived Sca-1- and c-kit-positive cells in peripheral blood after ischemia was significantly lower in the HSF1-KO mice than in the WT mice. BM stem/progenitor cells from HSF1-KO mice showed a significant decrease in their recruitment to ischemic tissue and in migration, adhesion, and survival when compared with WT mice. Blood flow recovery in the ischemic hindlimb significantly decreased in WT mice receiving BM reconstitution with donor cells from HSF1-KO mice. Conversely, blood flow recovery in the ischemic hindlimb significantly increased in HSF1-KO mice receiving BM reconstitution with donor cells from WT mice. These findings suggest that HSF1 contributes to ischemia-induced angiogenesis by regulating the mobilization and recruitment of BM-derived stem/progenitor cells.

  9. Autologous Endothelial Progenitor Cell-Seeding Technology and Biocompatibility Testing For Cardiovascular Devices in Large Animal Model

    OpenAIRE

    Jantzen, Alexandra E.; Lane, Whitney O.; Gage, Shawn M.; Haseltine, Justin M; Galinat, Lauren J; Jamiolkowski, Ryan M.; Lin, Fu-Hsiung; Truskey, George A.; Achneck, Hardean E.

    2011-01-01

    Implantable cardiovascular devices are manufactured from artificial materials (e.g. titanium (Ti), expanded polytetrafluoroethylene), which pose the risk of thromboemboli formation1,2,3. We have developed a method to line the inside surface of Ti tubes with autologous blood-derived human or porcine endothelial progenitor cells (EPCs)4. By implanting Ti tubes containing a confluent layer of porcine EPCs in the inferior vena cava (IVC) of pigs, we tested the improved biocompatibility of the cel...

  10. Endothelial Progenitor Cells Promote Directional Three-Dimensional Endothelial Network Formation by Secreting Vascular Endothelial Growth Factor

    OpenAIRE

    Yoshinori Abe; Yoshiyuki Ozaki; Junichi Kasuya; Kimiko Yamamoto; Joji Ando; Ryo Sudo; Mariko Ikeda; Kazuo Tanishita

    2013-01-01

    Endothelial progenitor cell (EPC) transplantation induces the formation of new blood-vessel networks to supply nutrients and oxygen, and is feasible for the treatment of ischemia and cardiovascular diseases. However, the role of EPCs as a source of proangiogenic cytokines and consequent generators of an extracellular growth factor microenvironment in three-dimensional (3D) microvessel formation is not fully understood. We focused on the contribution of EPCs as a source of proangiogenic cytoki...

  11. PRDM11 is dispensable for the maintenance and function of hematopoietic stem and progenitor cells

    DEFF Research Database (Denmark)

    Thoren, Lina A; Fog, Cathrine K; Jensen, Klaus T;

    2013-01-01

    Hematopoietic stem cells (HSC)(1) supply organisms with life-long output of mature blood cells. To do so, the HSC pool size has to be maintained by HSC self-renewing divisions. PRDM3 and PRDM16 have been documented to regulate HSC self-renewal, maintenance and function. We found Prdm11 to have...... similar expression patterns in the hematopoietic stem and progenitor cell (HSPC) compartments as Prdm3 and Prdm16. Therefore, we undertook experiments to test if PRDM11 regulates HSC self-renewal, maintenance and function by investigating the Prdm11(-/-) mice. Our data shows that phenotypic HSPCs...

  12. Fibrin scaffolds seeded with endothelial progenitor cells for tissue engineering applications

    OpenAIRE

    Magera, Angela; Barsotti, Maria Chiara; Lemmi, Monica; Armani, Chiara; Arici, Roberta; Iorio, Maria Carla; Soldani, Giorgio; Balbarini, Alberto; Di Stefano, Rossella

    2008-01-01

    Purpose To evaluate the use of fibrin as alternative biological scaffold for the in vitro culture of endothelial progenitor cells (EPC) Methods Fibrinogen (F, 4.5-36 mg/ml) and thrombin (T, 12.5-50 U/ml) were mixed to obtain the fibrin matrix and analysed by scanning electron microscopy (SEM and CRYO-SEM). EPC were obtained from human peripheral blood mononuclear cells and cultured for 1 week on the fibrin scaffolds at the concentration of 1 106 cells/cm2 in endothelial growth medium. As a co...

  13. Human fetal aorta-derived vascular progenitor cells: identification and potential application in ischemic diseases

    OpenAIRE

    Invernici, Gloria; Madeddu, Paolo; Emanueli, Costanza; Parati, Eugenio A.; Alessandri, Giulio

    2008-01-01

    Vasculogenesis, the formation of blood vessels in embryonic or fetal tissue mediated by immature vascular cells (i.e., angioblasts), is poorly understood. Here we report a summary of our recent studies on the identification of a population of vascular progenitor cells (VPCs) in human fetal aorta. These undifferentiated mesenchymal cells co-express endothelial and myogenic markers (CD133+, CD34+, KDR+, desmin+) and are localized in outer layer of the aortic stroma of 11–12 weeks old human fetu...

  14. Growth Induction and Low-Oxygen Apoptosis Inhibition of Human CD34+ Progenitors in Collagen Gels

    Directory of Open Access Journals (Sweden)

    Daniele Avitabile

    2013-01-01

    Full Text Available Various reports have indicated low survival of injected progenitors into unfavorable environments such as the ischemic myocardium or lower limb tissues. This represents a major bottleneck in stem-cell-based cardiovascular regenerative medicine. Strategies to enhance survival of these cells in recipient tissues have been therefore sought to improve stem cell survival and ensure long-term engraftment. In the present contribution, we show that embedding human cord blood-derived CD34+ cells into a collagen I-based hydrogel containing cytokines is a suitable strategy to promote stem cell proliferation and protect these cells from anoxia-induced apoptosis.

  15. Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions.

    Science.gov (United States)

    Rudzitis-Auth, Jeannette; Nenicu, Anca; Nickels, Ruth M; Menger, Michael D; Laschke, Matthias W

    2016-08-01

    The incorporation of endothelial progenitor cells (EPCs) into microvessels contributes to the vascularization of endometriotic lesions. Herein, we analyzed whether this vasculogenic process is regulated by estrogen. Estrogen- and vehicle-treated human EPCs were analyzed for migration and tube formation. Endometriotic lesions were induced in irradiated FVB/N mice, which were reconstituted with bone marrow from FVB/N-TgN (Tie2/green fluorescent protein) 287 Sato mice. The animals were treated with 100 μg/kg β-estradiol 17-valerate or vehicle (control) over 7 and 28 days. Lesion growth, cyst formation, homing of green fluorescent protein(+)/Tie2(+) EPCs, vascularization, cell proliferation, and apoptosis were analyzed by high-resolution ultrasonography, caliper measurements, histology, and immunohistochemistry. Numbers of blood circulating EPCs were assessed by flow cytometry. In vitro, estrogen-treated EPCs exhibited a higher migratory and tube-forming capacity when compared with controls. In vivo, numbers of circulating EPCs were not affected by estrogen. However, estrogen significantly increased the number of EPCs incorporated into the lesions' microvasculature, resulting in an improved early vascularization. Estrogen further stimulated the growth of lesions, which exhibited massively dilated glands with a flattened layer of stroma. This was mainly because of an increased glandular secretory activity, whereas cell proliferation and apoptosis were not markedly affected. These findings indicate that vasculogenesis in endometriotic lesions is dependent on estrogen, which adds a novel hormonally regulated mechanism to the complex pathophysiology of endometriosis. PMID:27315780

  16. Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Peter E Westerweel

    Full Text Available BACKGROUND: Circulating Endothelial Progenitor Cell (EPC levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment. METHODS: Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+Flk-1(+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+ hematopoietic progenitor cells (HPC and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. RESULTS: In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. CONCLUSION: EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

  17. Impaired Endothelial Progenitor Cell Mobilization and Dysfunctional Bone Marrow Stroma in Diabetes Mellitus

    Science.gov (United States)

    Rafii, Shahin; Jaspers, Janneke E.; White, Ian A.; Hooper, Andrea T.; Doevendans, Pieter A.; Verhaar, Marianne C.

    2013-01-01

    Background Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired –at least partly– due to dysfunction of the bone marrow stromal compartment. Methods Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1+Flk-1+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34+ hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell–endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. Results In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. Conclusion EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients. PMID:23555959

  18. Patient-specific cardiovascular progenitor cells derived from integration-free induced pluripotent stem cells for vascular tissue regeneration.

    Science.gov (United States)

    Hu, Jiang; Wang, Yongyu; Jiao, Jiao; Liu, Zhongning; Zhao, Chao; Zhou, Zhou; Zhang, Zhanpeng; Forde, Kaitlynn; Wang, Lunchang; Wang, Jiangang; Baylink, David J; Zhang, Xiao-Bing; Gao, Shaorong; Yang, Bo; Chen, Y Eugene; Ma, Peter X

    2015-12-01

    Tissue-engineered blood vessels (TEBVs) are promising in regenerating a live vascular replacement. However, the vascular cell source is limited, and it is crucial to develop a scaffold that accommodates new type of vascular progenitor cells and facilitates in vivo lineage specification of the cells into functional vascular smooth muscle cells (VSMCs) to regenerate vascular tissue. In the present study, integration-free human induced pluripotent stem cells (hiPSCs) were established from patient peripheral blood mononuclear cells through episomal vector nucleofection of reprogramming factors. The established hiPSCs were then induced into mesoderm-originated cardiovascular progenitor cells (CVPCs) with a highly efficient directed lineage specification method. The derived CVPCs were demonstrated to be able to differentiate into functional VSMCs. Subcutaneous implantation of CVPCs seeded on macroporous nanofibrous poly(l-lactide) scaffolds led to in vivo VSMC lineage specification and matrix deposition inside the scaffolds. In summary, we established integration-free patient-specific hiPSCs from peripheral blood mononuclear cells, derived CVPCs through directed lineage specification, and developed an advanced scaffold for these progenitor cells to further differentiate in vivo into VSMCs and regenerate vascular tissue in a subcutaneous implantation model. This study has established an efficient patient-specific approach towards in vivo regeneration of vascular tissue.

  19. Galactic Constraints on Supernova Progenitor Models

    CERN Document Server

    Acharova, I; Mishurov, Yu; Kovtyukh, V

    2013-01-01

    We undertake a statistical analysis of the radial abundance distributions in the Galactic disk within a theoretical framework for Galactic chemical evolution which incorporates the influence of spiral arms. 1) The mean mass of oxygen ejected per core-collapse SNe (CC SNe) event (which are concentrated within spiral arms) is $\\sim$0.27 M$_{\\odot}$; 2) the mean mass of iron ejected by `tardy' Type Ia SNe (SNeIa; progenitors of whom are older/longer-lived stars with ages $\\simgt$100 Myr and up to several Gyr, which do not concentrate within spiral arms) is $\\sim$0.58 M$_{\\odot}$; 3) the upper mass of iron ejected by prompt SNeIa (SNe whose progenitors are younger/shorter-lived stars with ages $\\simlt$100 Myr, which are concentrated within spiral arms) is $\\leq$0.23 M$_{\\odot}$ per event; 4) the corresponding mean mass of iron produced by CC SNe is $\\leq$0.04 M$_{\\odot}$ per event; (v) short-lived SNe (core-collapse or prompt SNeIa) supply $\\sim$85% of the Galactic disk's iron. The inferred low mean mass of oxyge...

  20. Endothelial Progenitor Cells Enter the Aging Arena.

    Directory of Open Access Journals (Sweden)

    Kate eWilliamson

    2012-02-01

    Full Text Available Age is a significant risk factor for the development of vascular diseases, such as atherosclerosis. Although pharmacological treatments, including statins and anti-hypertensive drugs, have improved the prognosis for patients with cardiovascular disease, it remains a leading cause of mortality in those aged 65 years and over. Furthermore, given the increased life expectancy of the population in developed countries, there is a clear need for alternative treatment strategies. Consequently, the relationship between aging and progenitor cell-mediated repair is of great interest. Endothelial progenitor cells (EPCs play an integral role in the cellular repair mechanisms for endothelial regeneration and maintenance. However, EPCs are subject to age-associated changes that diminish their number in circulation and function, thereby enhancing vascular disease risk. A great deal of research is aimed at developing strategies to harness the regenerative capacity of these cells.In this review, we discuss the current understanding of the cells termed ‘EPCs’, examine the impact of age on EPC-mediated repair and identify therapeutic targets with potential for attenuating the age-related decline in vascular health via beneficial actions on EPCs.

  1. Progenitor cells in arteriosclerosis: good or bad guys?

    Science.gov (United States)

    Campagnolo, Paola; Wong, Mei Mei; Xu, Qingbo

    2011-08-15

    Accumulating evidence indicates that the mobilization and recruitment of circulating or tissue-resident progenitor cells that give rise to endothelial cells (ECs) and smooth muscle cells (SMCs) can participate in atherosclerosis, neointima hyperplasia after arterial injury, and transplant arteriosclerosis. It is believed that endothelial progenitor cells do exist and can repair and rejuvenate the arteries under physiologic conditions; however, they may also contribute to lesion formation by influencing plaque stability in advanced atherosclerotic plaque under specific pathologic conditions. At the same time, smooth muscle progenitors, despite their capacity to expedite lesion formation during restenosis, may serve to promote atherosclerotic plaque stabilization by producing extracellular matrix proteins. This profound evidence provides support to the hypothesis that both endothelial and smooth muscle progenitors may act as a double-edged sword in the pathogenesis of arteriosclerosis. Therefore, the understanding of the regulatory networks that control endothelial and smooth muscle progenitor differentiation is undoubtedly fundamental both for basic research and for improving current therapeutic avenues for atherosclerosis. We update the progress in progenitor cell study related to the development of arteriosclerosis, focusing specifically on the role of progenitor cells in lesion formation and discuss the controversial issues that regard the origins, frequency, and impact of the progenitors in the disease.

  2. EGFR signaling regulates the proliferation of Drosophila adult midgut progenitors

    OpenAIRE

    Jiang, Huaqi; Edgar, Bruce A.

    2009-01-01

    In holometabolous insects, the adult appendages and internal organs form anew from larval progenitor cells during metamorphosis. As described here, the adult Drosophila midgut, including intestinal stem cells (ISCs), develops from adult midgut progenitor cells (AMPs) that proliferate during larval development in two phases. Dividing AMPs first disperse, but later proliferate within distinct islands, forming large cell clusters that eventually fuse during metamorphosis ...

  3. SH2-inositol phosphatase 1 negatively influences early megakaryocyte progenitors.

    Directory of Open Access Journals (Sweden)

    Lia E Perez

    Full Text Available BACKGROUND: The SH2-containing-5'inositol phosphatase-1 (SHIP influences signals downstream of cytokine/chemokine receptors that play a role in megakaryocytopoiesis, including thrombopoietin, stromal-cell-derived-Factor-1/CXCL-12 and interleukin-3. We hypothesize that SHIP might control megakaryocytopoiesis through effects on proliferation of megakaryocyte progenitors (MKP and megakaryocytes (MK. METHODOLOGY AND PRINCIPAL FINDINGS: Herein, we report the megakaryocytic phenotype and MK functional assays of hematopoietic organs of two strains of SHIP deficient mice with deletion of the SHIP promoter/first exon or the inositol phosphatase domain. Both SHIP deficient strains exhibit a profound increase in MKP numbers in bone marrow (BM, spleen and blood as analyzed by flow cytometry (Lin(-c-Kit+CD41+ and functional assays (CFU-MK. SHIP deficient MKP display increased phosphorylation of Signal Transducers and Activators of Transcription 3 (STAT-3, protein kinase B (PKB/AKT and extracellular signal-regulated kinases (ERKs. Despite increased MKP content, total body number of mature MK (Lin(-c-kit(-CD41+ are not significantly changed as SHIP deficient BM contains reduced MK while spleen MK numbers are increased. Reduction of CXCR-4 expression in SHIP deficient MK may influence MK localization to the spleen instead of the BM. Endomitosis, process involved in MK maturation, was preserved in SHIP deficient MK. Circulating platelets and red blood cells are also reduced in SHIP deficient mice. CONCLUSIONS/SIGNIFICANCE: SHIP may play an important role in regulation of essential signaling pathways that control early megakaryocytopoiesis in vivo.

  4. Blood Types

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Blood Types KidsHealth > For Teens > Blood Types Print A A ... or straight hair instead of curly. ...Make Eight Blood Types The different markers that can be found in ...

  5. Effect of human neural progenitor cells on injured spinal cord

    Institute of Scientific and Technical Information of China (English)

    XU Guang-hui; BAI Jin-zhu; CAI Qin-lin; LI Xiao-xia; LI Ling-song; SHEN Li

    2005-01-01

    Objective: To study whether human neural progenitor cells can differentiate into neural cells in vivo and improve the recovery of injured spinal cord in rats.Methods: Human neural progenitor cells were transplanted into the injured spinal cord and the functional recovery of the rats with spinal cord contusion injury was evaluated with Basso-Beattie-Bresnahan (BBB) locomotor scale and motor evoked potentials. Additionally, the differentiation of human neural progenitor cells was shown by immunocytochemistry.Results: Human neural progenitor cells developed into functional cells in the injured spinal cord and improved the recovery of injured spinal cord in both locomotor scores and electrophysiological parameters in rats.Conclusions: Human neural progenitor cells can treat injured spinal cord, which may provide a new cell source for research of clinical application.

  6. Immunoelectrophoresis - blood

    Science.gov (United States)

    IEP - serum; Immunoglobulin electrophoresis - blood; Gamma globulin electrophoresis; Serum immunoglobulin electrophoresis ... A blood sample is needed. For information on how this is done, see: Venipuncture

  7. Mobilization of bone marrow-derived progenitor cells in acute coronary syndromes.

    Directory of Open Access Journals (Sweden)

    Wojciech Wojakowski

    2005-12-01

    Full Text Available Two hypotheses explain the role of adult progenitor cells in myocardial regeneration. Stem cell plasticity which involves mobilization of stem cells from the bone marrow and other niches, homing to the area of tissue injury and transdifferentiation into functional cardiomyocytes. Alternative hypothesis is based on the observations that bone marrow harbors a heterogenous population of cells positive for CXCR4 - receptor for chemokine SDF-1. This population of non-hematopoietic cells expresses genes specific for early muscle, myocardial and endothelial progenitor cells (EPC. These tissue-committed stem cells circulate in the peripheral blood at low numbers and can be mobilized by hematopoietic cytokines in the setting of myocardial ischemia. Endothelial precursors capable of transforming into mature, functional endothelial cells are present in the pool of peripheral mononuclear cells in circulation. Their number significantly increases in acute myocardial infarction (AMI with subsequent decrease after 1 month, as well as in patients with unstable angina in comparison to stable coronary heart disease (CHD. There are numerous physiological and pathological stimuli which influence the number of circulating EPC such as regular physical activity, medications (statins, PPAR-gamma agonists, estrogens, as well as numerous inflammatory and hematopoietic cytokines. Mobilization of stem cells in AMI involves not only the endothelial progenitors but also hematopoietic, non-hematopoietic stem cells and most probably the mesenchymal cells. In healthy subjects and patients with stable CHD, small number of circulating CD34+, CXCR4+, CD117+, c-met+ and CD34/CD117+ stem cells can be detected. In patients with AMI, a significant increase in CD34+/CXCR4+, CD117+, c-met+ and CD34/CD117+ stem cell number the in peripheral blood was demonstrated with parallel increase in mRNA expression for early cardiac, muscle and endothelial markers in peripheral blood mononuclear

  8. Comparison of haematopoietic stem cell engraftment through the retro-orbital venous sinus and the lateral vein: alternative routes for bone marrow transplantation in mice.

    Science.gov (United States)

    Leon-Rico, D; Fernández-García, M; Aldea, M; Sánchez, R; Peces-Barba, M; Martinez-Palacio, J; Yáñez, R M; Almarza, E

    2015-04-01

    Bone marrow transplantation in mice is performed by intravenous administration of haematopoietic repopulating cells, usually via the lateral tail vein. This technique can be technically challenging to carry out and may cause distress to the mice. The retro-orbital sinus is a large area where there is a confluence of several vessels that provides an alternative route for intravenous access. Retro-orbital injection, although aesthetically unpleasant, can be performed rapidly without requiring mechanical restriction or heat-induced vasodilation. In addition, this technique can be easily learned by novice manipulators. This route of administration has been reported for use in bone marrow transplantation but there is no comparison of retro-orbital and tail vein injections reported for this specific purpose, although both routes have been compared for many other applications. Here, we provide for the first time a comprehensive comparison between tail vein and retro-orbital injections for two different bone marrow transplant scenarios in P3B and B6D2F1 mice. In both cases, no significant differences regarding donor engraftment were observed between mice transplanted using each of the techniques. Haematological counts and leukocyte subpopulation distribution were practically identical between both animal groups. Moreover, donor engraftment levels were less homogenous when cells were transplanted by tail vein injection, probably due to a higher risk of failure associated with this technique. All these data suggest that retro-orbital injection is a compelling alternative to conventional tail vein injection for bone marrow transplant in mice, providing similar and more homogenous haematopoietic reconstitution.

  9. Progenitor model of cosmic ray knee

    Science.gov (United States)

    Bijay, Biplab; Bhadra, Arunava

    2016-01-01

    The primary energy spectrum of cosmic rays exhibits a knee at about 3 PeV where a change in the spectral index occurs. Despite many efforts, the origin of such a feature in the spectrum is not satisfactorily solved yet. Here it is proposed that the steepening of the spectrum beyond the knee may be a consequence of the mass distribution of the progenitor of the cosmic ray source. The proposed speculative model can account for all the major observed features of cosmic rays without invoking any fine tuning to match flux or spectra at any energy point. The prediction of the proposed model regarding the primary composition scenario beyond the knee is quite different from most of the prevailing models of the knee, and thereby can be discriminated from precise experimental measurement of the primary composition.

  10. PET imaging of adoptive progenitor cell therapies.

    Energy Technology Data Exchange (ETDEWEB)

    Gelovani, Juri G.

    2008-05-13

    Objectives. The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive “tracking” of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to

  11. PET imaging of adoptive progenitor cell therapies

    International Nuclear Information System (INIS)

    The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive 'tracking' of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to stem cell imaging

  12. Multipotent pancreas progenitors: Inconclusive but pivotal topic.

    Science.gov (United States)

    Jiang, Fang-Xu; Morahan, Grant

    2015-12-26

    The establishment of multipotent pancreas progenitors (MPP) should have a significant impact not only on the ontology of the pancreas, but also for the translational research of glucose-responding endocrine β-cells. Deficiency of the latter may lead to the pandemic type 1 or type 2 diabetes mellitus, a metabolic disorder. An ideal treatment of which would potentially be the replacement of destroyed or failed β-cells, by restoring function of endogenous pancreatic endocrine cells or by transplantation of donor islets or in vitro generated insulin-secreting cells. Thus, considerable research efforts have been devoted to identify MPP candidates in the pre- and post-natal pancreas for the endogenous neogenesis or regeneration of endocrine insulin-secreting cells. In order to advance this inconclusive but critical field, we here review the emerging concepts, recent literature and newest developments of potential MPP and propose measures that would assist its forward progression. PMID:26730269

  13. Exercise-induced norepinephrine decreases circulating hematopoietic stem and progenitor cell colony-forming capacity.

    Directory of Open Access Journals (Sweden)

    Julia M Kröpfl

    Full Text Available A recent study showed that ergometry increased circulating hematopoietic stem and progenitor cell (CPC numbers, but reduced hematopoietic colony forming capacity/functionality under normoxia and normobaric hypoxia. Herein we investigated whether an exercise-induced elevated plasma free/bound norepinephrine (NE concentration could be responsible for directly influencing CPC functionality. Venous blood was taken from ten healthy male subjects (25.3+/-4.4 yrs before and 4 times after ergometry under normoxia and normobaric hypoxia (FiO2<0.15. The circulating hematopoietic stem and progenitor cell numbers were correlated with free/bound NE, free/bound epinephrine (EPI, cortisol (Co and interleukin-6 (IL-6. Additionally, the influence of exercise-induced NE and blood lactate (La on CPC functionality was analyzed in a randomly selected group of subjects (n = 6 in vitro under normoxia by secondary colony-forming unit granulocyte macrophage assays. Concentrations of free NE, EPI, Co and IL-6 were significantly increased post-exercise under normoxia/hypoxia. Ergometry-induced free NE concentrations found in vivo showed a significant impairment of CPC functionality in vitro under normoxia. Thus, ergometry-induced free NE was thought to trigger CPC mobilization 10 minutes post-exercise, but as previously shown impairs CPC proliferative capacity/functionality at the same time. The obtained results suggest that an ergometry-induced free NE concentration has a direct negative effect on CPC functionality. Cortisol may further influence CPC dynamics and functionality.

  14. Circulating endothelial progenitor cells in traumatic brain injury: an emerging therapeutic target?

    Institute of Scientific and Technical Information of China (English)

    WEI Hui-jie; JIANG Rong-cai; LIU Li; ZHANG Jian-ning

    2010-01-01

    Traumatic brain injury (TBI) is a major cause ofmortality and morbidity in the world. Recent clinical investigations and basic researches suggest that strategies to improve angiogenesis following TBI may provide promising opportunities to improve clinical outcomes and brain functional recovery. More and more evidences show that circulating endothelial progenitor cells (EPCs), which have been identified in the peripheral blood, may play an important role in the pathologic and physiological angiogenesis in adults. Moreover, impressive data demonstrate that EPCs are mobilized from bone marrow to blood circulation in response to traumatic or inflammatory stimulations.In this review, we discussed the role of EPCs in the repair of brain injury and the possible therapeutic implication for functional recovery of TBl in the future.

  15. Preclinical activity of 17 beta-[N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-L-alanyl]-5 alpha-dihydrotestosterone (E91) against tumour colony forming units and haematopoietic progenitor cells.

    Science.gov (United States)

    Rank, P; Peter, R; Depenbrock, H; Eisenbrand, G; Schmid, P; Pitzl, H; Hanauske, A R

    1999-06-01

    E91 (17 beta-[N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-L-alanyl]-5 alpha-dihydrotestosterone) (CNC-ala-DHT) is a newly synthesised alkylating compound consisting of N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-L-alanine (CNC-ala) as the alkylating moiety and of 5 alpha-dihydrotestosterone (DHT) as a steroid carrier molecule. We studied the antitumour activity of E91 (final concentrations: 0.1, 1, 10 and 30 mumol/l) against freshly explanted human tumours, using an in vitro soft agar cloning system. A total of 54 tumour samples was evaluated using 1 h-exposure and 51 tumour specimens were studied using a continuous exposure for 21-28 days. In addition, the compound's activity was compared with other clinically used anticancer agents. After short-term exposure, 49 of 53 evaluable specimens (92%) had adequate colony formation, as compared with 49 of 50 (98%) after long-term exposure. After short-term exposure, E91 exhibited only marginal antitumour activity. However, in long-term exposure experiments, E91 had marked and concentration-dependent antitumour activity (P 10 mumol/l, E91 was as active as the other clinically used antineoplastic agents and at 30 mumol/l, E91 was significantly more active than 5-fluorouracil (P = 0.041). E91 showed activity against a wide spectrum of tumour types. The highest activity was observed against colorectal carcinomas (3/4 tumour specimens inhibited at 30 mumol/l). Sensitivity was also high remarkable in breast cancer specimens with 3/6 specimens inhibited at 30 mumol/l. In vitro myelotoxicity was less than that of doxorubicin. At 30 mumol/l, E91 induced a reduction of colony forming units-granulocyte macrophage (CFU-GM) to only 53% of control and of CFU-GEMM to 20% of control. We conclude that because of broad activity and reduced myelotoxicity further clinical development of E91 appears warranted. PMID:10533486

  16. [Promising technologies of packed red blood cells production and storage].

    Science.gov (United States)

    Maksimov, A G; Golota, A S; Krassiĭ, A B

    2013-10-01

    The current article is dedicated to promising technologies of packed red blood cells production and storage. The following new technical approaches are presented: (1) erythrocytes storage in strict anaerobic argon-hydrogen environment, (2) lyophilization of erythrocyte suspension by its atomization in nitrogen gas, (3) lyophilization of erythrocytes by directional freezing under the influence of radio frequency radiation, (4) automated pharming of antigen free packed red blood cells from progenitor cell directly at the battlefield. PMID:24611298

  17. [Promising technologies of packed red blood cells production and storage].

    Science.gov (United States)

    Maksimov, A G; Golota, A S; Krassiĭ, A B

    2013-10-01

    The current article is dedicated to promising technologies of packed red blood cells production and storage. The following new technical approaches are presented: (1) erythrocytes storage in strict anaerobic argon-hydrogen environment, (2) lyophilization of erythrocyte suspension by its atomization in nitrogen gas, (3) lyophilization of erythrocytes by directional freezing under the influence of radio frequency radiation, (4) automated pharming of antigen free packed red blood cells from progenitor cell directly at the battlefield.

  18. Artificial blood

    Directory of Open Access Journals (Sweden)

    Sarkar Suman

    2008-01-01

    Full Text Available Artificial blood is a product made to act as a substitute for red blood cells. While true blood serves many different functions, artificial blood is designed for the sole purpose of transporting oxygen and carbon dioxide throughout the body. Depending on the type of artificial blood, it can be produced in different ways using synthetic production, chemical isolation, or recombinant biochemical technology. Development of the first blood substitutes dates back to the early 1600s, and the search for the ideal blood substitute continues. Various manufacturers have products in clinical trials; however, no truly safe and effective artificial blood product is currently marketed. It is anticipated that when an artificial blood product is available, it will have annual sales of over $7.6 billion in the United States alone.

  19. ZFP36L2 is required for self-renewal of early burst-forming unit erythroid progenitors.

    Science.gov (United States)

    Zhang, Lingbo; Prak, Lina; Rayon-Estrada, Violeta; Thiru, Prathapan; Flygare, Johan; Lim, Bing; Lodish, Harvey F

    2013-07-01

    Stem cells and progenitors in many lineages undergo self-renewing divisions, but the extracellular and intracellular proteins that regulate this process are largely unknown. Glucocorticoids stimulate red blood cell formation by promoting self-renewal of early burst-forming unit-erythroid (BFU-E) progenitors. Here we show that the RNA-binding protein ZFP36L2 is a transcriptional target of the glucocorticoid receptor (GR) in BFU-Es and is required for BFU-E self-renewal. ZFP36L2 is normally downregulated during erythroid differentiation from the BFU-E stage, but its expression is maintained by all tested GR agonists that stimulate BFU-E self-renewal, and the GR binds to several potential enhancer regions of ZFP36L2. Knockdown of ZFP36L2 in cultured BFU-E cells did not affect the rate of cell division but disrupted glucocorticoid-induced BFU-E self-renewal, and knockdown of ZFP36L2 in transplanted erythroid progenitors prevented expansion of erythroid lineage progenitors normally seen following induction of anaemia by phenylhydrazine treatment. ZFP36L2 preferentially binds to messenger RNAs that are induced or maintained at high expression levels during terminal erythroid differentiation and negatively regulates their expression levels. ZFP36L2 therefore functions as part of a molecular switch promoting BFU-E self-renewal and a subsequent increase in the total numbers of colony-forming unit-erythroid (CFU-E) progenitors and erythroid cells that are generated.

  20. On Measuring the Metallicity of Supernovae Type Ia Progenitors

    CERN Document Server

    Miles, Broxton J; Townsley, Dean M; Timmes, F X; Jackson, Aaron P; Calder, Alan C; Brown, Edward F

    2015-01-01

    In Type Ia Supernovae (\\sneia), the relative abundances of chemical elements are affected by the neutron excess in the composition of the progenitor white dwarf. Since these products leave signatures in the spectra near maximum light, spectral features may be used to constrain the composition of the progenitor. We calculate the nucleosynthetic yields for three \\snia simulations for a wide range of progenitor metallicities, and calculate synthetic light curves and spectra to explore correlations between progenitor metallicity and the strength of spectral features. We use two 2D simulations of the deflagration-detonation-transition scenario with different $^{56}$Ni yields and the W7 simulation to control for differences between explosion models and total yields. While the overall yields of intermediate mass elements (16 $<$ A $\\leq$ 40) differ between the three cases, trends in the yields are similar. With increasing metallicity, $^{28}$Si yields remain nearly constant, $^{40}$Ca yields decline, and Ti and $...

  1. Senegenin promotes in vitro proliferation of human neural progenitor cells

    Institute of Scientific and Technical Information of China (English)

    Fang Shi; Zhigang Liang; Zixuan Guo; Ran Li; Fen Yu; Zhanjun Zhang; Xuan Wang; Xiaomin Wang

    2011-01-01

    Senegenin, an effective component of Polygala tenuifolia root extract, promotes proliferation and differentiation of neural progenitor cells in the hippocampus.However, the effects of senegenin on mesencephalon-derived neural progenitor cells remain poorly understood.Cells from a ventral mesencephalon neural progenitor cell line (ReNcell VM) were utilized as models for pharmaceutical screening.The effects of various senegenin concentrations on cell proliferation were analyzed,demonstrating that high senegenin concentrations (5, 10, 50, and 100 pmo/L), particularly 50 pmol/L, significantly promoted proliferation of ReNcell VM cells.In the mitogen-activated protein kinase signal transduction pathway, senegenin significantly increased phosphorylation levels of extracellular signal-regulated kinases.Moreover, cell proliferation was suppressed by extracellular signal-regulated kinase inhibitors.Results suggested that senegenin contributed to in vitro proliferation of human neural progenitor cells by upregulating phosphorylation of extracellular signal-regulated kinase.

  2. Observational clues to the progenitors of Type-Ia supernovae

    CERN Document Server

    Maoz, Dan; Nelemans, Gijs

    2013-01-01

    Type-Ia supernovae (SNe Ia) are important distance indicators, element factories, cosmic-ray accelerators, kinetic-energy sources in galaxy evolution, and endpoints of stellar binary evolution. It has long been clear that a SN Ia must be the runaway thermonuclear explosion of a degenerate carbon-oxygen stellar core, most likely a white dwarf (WD). However, the specific progenitor systems of SNe Ia, and the processes that lead to their ignition, have not been identified. Two broad classes of progenitor binary systems have long been considered: single-degenerate (SD), in which a WD gains mass from a non-degenerate star; and double-degenerate (DD), involving the merger of two WDs. New theoretical work has enriched these possibilities with some interesting updates and variants. We review the significant recent observational progress in addressing the progenitor problem. We consider clues that have emerged from the observed properties of the various proposed progenitor populations, from studies of their sites, pre...

  3. Blockade of prostaglandin E2 signaling through EP1 and EP3 receptors attenuates Flt3L-dependent dendritic cell development from hematopoietic progenitor cells

    Science.gov (United States)

    Singh, Pratibha; Hoggatt, Jonathan; Hu, Peirong; Speth, Jennifer M.; Fukuda, Seiji; Breyer, Richard M.

    2012-01-01

    Dendritic cell (DC) homeostasis, like all mature blood cells, is maintained via hierarchal generation from hematopoietic precursors; however, little is known about the regulatory mechanisms governing DC generation. Here, we show that prostaglandin E2 (PGE2) is required for optimal Flt3 ligand–mediated DC development and regulates expression of the Flt3 receptor on DC-committed progenitor cells. Inhibition of PGE2 biosynthesis reduces Flt3-mediated activation of STAT3 and expression of the antiapoptotic protein survivin, resulting in increased apoptosis of DC-committed progenitor cells. Reduced DC development caused by diminished PGE2 signaling is reversed by overexpression of Flt3 or survivin in DC progenitors and conversely is mimicked by STAT3 inhibition. PGE2 regulation of DC generation is specifically mediated through the EP1 and EP3 G protein PGE2 receptors. These studies define a novel DC progenitor regulatory pathway in which PGE2 signaling through EP1/EP3 receptors regulates Flt3 expression and downstream STAT3 activation and survivin expression, required for optimal DC progenitor survival and DC development in vivo. PMID:22110249

  4. Effects of a 2-step culture with cytokine combinations on megakaryocytopoiesis and thrombopoiesis from carbon-ion beam-irradiated human hematopoietic stem/progenitor cells

    International Nuclear Information System (INIS)

    To evaluate whether the continuous treatment of two cytokine combinations is effective in megakaryocytopoiesis and thrombopoiesis in hematopoietic stem/progenitor cells exposed to heavy ion beams, the effects of a 2-step culture by a combination of recombinant human interleukin-3 (IL-3)+stem cell factor (SCF)+thrombopoietin (TPO), which just slightly protected against carbon-ion beam-induced damages, and a combination of IL-3+TPO, which selectively stimulated the differentiation of the hematopoietic stem/progenitor cells to megakaryocytes and platelets, were examined. CD34+-hematopoietic stem/progenitor cells isolated from the human placental and umbilical cord blood were exposed to carbon-ion beams (linear energy transfer (LET)=50 keV/μm) at 2 Gy. These cells were cultured under three cytokine conditions. The number of megakaryocytes, platelets and hematopoietic progenitors were assessed using a flow cytometer and a clonogenic assay at 14 and 21 days after irradiation, respectively. However, the efficacy of each 2-step culture was equal or lower than that of using the IL-3+SCF+TPO combination alone and the 2-step culture could not induce megakaryocytes and platelets from hematopoietic stem/progenitor cells exposed to high LET-radiation such as carbon-ion beams. Therefore, additional cytokines and/or hematopoietic promoting compounds might be required to overcome damage to hematopoietic cells by high LET radiation. (author)

  5. Moderate traumatic brain injury promotes proliferation of quiescent neural progenitors in the adult hippocampus

    OpenAIRE

    Gao, Xiang; Enikolopov, Grigori; Chen, Jinhui

    2009-01-01

    Recent evidence shows that traumatic brain injury (TBI) regulates proliferation of neural stem/progenitor cells in the dentate gyrus (DG) of adult hippocampus. There are distinct classes of neural stem/progenitor cells in the adult DG, including quiescent neural progenitors (QNPs), which carry stem cell properties, and their progeny, amplifying neural progenitors (ANPs). The response of each class of progenitors to TBI is not clear. We here used a transgenic reporter Nestin-GFP mouse line, in...

  6. Endothelial progenitors in sepsis: vox clamantis in deserto?

    OpenAIRE

    Goligorsky, Michael S

    2011-01-01

    In this issue of Critical Care, Patschan and colleagues present a study of endothelial progenitor cells (EPCs) in patients with sepsis. The importance of this study is in focusing attention on several frequently ignored aspects of sepsis. Among those are the phenomenon of microvascular dysfunction, which is potentially responsible for profound metabolic perturbations at the tissue level, and the role of endothelial progenitors in repair processes. Other important aspects of the study are the ...

  7. Endometrial stem/progenitor cells: the first 10 years

    OpenAIRE

    Gargett, Caroline E; Schwab, Kjiana E.; Deane, James A

    2015-01-01

    BACKGROUND The existence of stem/progenitor cells in the endometrium was postulated many years ago, but the first functional evidence was only published in 2004. The identification of rare epithelial and stromal populations of clonogenic cells in human endometrium has opened an active area of research on endometrial stem/progenitor cells in the subsequent 10 years. METHODS The published literature was searched using the PubMed database with the search terms ‘endometrial stem cells and menstru...

  8. Human pancreatic islet progenitor cells demonstrate phenotypic plasticity in vitro

    Indian Academy of Sciences (India)

    Maithili P Dalvi; Malati R Umrani; Mugdha V Joglekar; Anandwardhan A Hardikar

    2009-10-01

    Phenotypic plasticity is a phenomenon that describes the occurrence of 2 or more distinct phenotypes under diverse conditions. This article discusses the work carried out over the past few years in understanding the potential of human pancreatic islet-derived progenitors for cell replacement therapy in diabetes. The phenotypic plasticity exhibited by pancreatic progenitors during reversible epithelial-to-mesenchymal transition (EMT) and possible role of microRNAs in regulation of this process is also presented herein.

  9. Osteocytes serve as a progenitor cell of osteosarcoma

    OpenAIRE

    Sottnik, Joseph L.; Campbell, Brittany; Mehra, Rohit; Behbahani-Nejad, Omid; Hall, Christopher L.; Keller, Evan T.

    2014-01-01

    Osteosarcoma (OSA) is the most common primary bone tumor in humans. However, the cell of origin of OSA is not clearly defined although there is evidence that osteoblasts may serve as OSA progenitors. The role of osteocytes, terminally differentiated osteoblasts, as OSA progenitors has yet to be described. Analysis of patient cDNA from publicly available microarray data revealed that patients with OSA have increased expression of dentin matrix phosphoprotein 1 (DMP1), a marker of osteocytes. A...

  10. Lung Stem and Progenitor Cells in Tissue Homeostasis and Disease

    OpenAIRE

    Leeman, Kristen T.; Fillmore, Christine M.; Kim, Carla F.

    2014-01-01

    The mammalian lung is a complex organ containing numerous putative stem/progenitor cell populations that contribute to region-specific tissue homeostasis and repair. In this review, we discuss recent advances in identifying and studying these cell populations in the context of lung homeostasis and disease. Genetically engineered mice now allow for lineage tracing of several lung stem and progenitor cell populations in vivo during different types of lung injury repair. Using specific sets of c...

  11. Blood smear

    Science.gov (United States)

    ... osmotic fragility ) Deficiency of an enzyme called lecithin cholesterol acyl transferase Abnormalities of hemoglobin , the protein in ... sickle and Pappenheimer Red blood cells, target cells Formed elements of blood References Bain BJ. The peripheral ...

  12. Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Yu-Qing Li

    2016-06-01

    Full Text Available Mammalian tissue-specific stem cells and progenitors demonstrate differential DNA damage response. Neural progenitors in dentate gyrus of the hippocampus are known to undergo apoptosis after irradiation. Using a mouse model of hippocampal neuronal development, we characterized the apoptosis sensitivity of the different neural progenitor subpopulations in adult mouse dentate gyrus after irradiation. Two different bromodeoxyuridine incorporation paradigms were used for cell fate mapping. We identified two apoptosis sensitive neural progenitor subpopulations after irradiation. The first represented non-proliferative and non-newborn neuroblasts and immature neurons that expressed doublecortin, calretinin or both. The second consisted of proliferative intermediate neural progenitors. The putative radial glia-like neural stem cells or type-1 cells, regardless of proliferation status, were apoptosis resistant after irradiation. There was no evidence of radiation-induced apoptosis in the absence of the Trp53 (p53 gene but absence of Cdkn1a (p21 did not alter the apoptotic response. Upregulation of nuclear p53 was observed in neuroblasts after irradiation. We conclude that adult hippocampal neural progenitors may demonstrate differential p53-dependent apoptosis sensitivity after irradiation.

  13. Possible Progenitor of Special Supernova Type Detected

    Science.gov (United States)

    2008-04-01

    caused by material being pulled off a companion star onto the white dwarf, fusion of this material on the surface of the star should heat the star and produce a strong source of X-radiation prior to the explosion. Once the supernova explosion occurs, the white dwarf is expected to be completely destroyed and then would be undetectable in X-rays. In the merger scenario, the intensity of X-ray emission prior to the explosion is expected to be much weaker. Based on the detection of a fairly strong X-ray source at approximately the position of SN 2007on 4 years before the explosion, Voss and Nelemans conclude that the data support the scenario where matter is pulled off a companion star. The small number of X-ray sources in the field implies that there is only a small chance of an unrelated source being so close by coincidence. Also, the X-ray source has similar properties to those expected for fusion on a white dwarf, unlike most X-ray sources in the sky. However, in follow-up studies, Voss, Nelemans and colleagues Gijs Roelofs (Harvard-Smithsonian Center for Astrophysics, Cambridge, Mass.) and Cees Bassa (McGill University, Canada) used higher-quality optical images to better determine the supernova's position. This work, which is not yet published, shows a small, but significant difference in the measured positions of the supernova and the X-ray source, suggesting the source may not be the progenitor. Follow-up Chandra observations hint that the X-ray object has disappeared, but further observations are needed to finally decide whether the source was the progenitor or not. The team is also applying this new method to other supernovas and has high hopes that they will eventually succeed in identifying the elusive cause of at least some of these explosions. "We're very excited about opening up a new way of studying supernovas, even though we're not sure that we've seen this particular stellar bomb before it exploded," said Gijs Roelofs. "We're very confident that we

  14. Binary progenitor models of type IIb supernovae

    CERN Document Server

    Claeys, J S W; Pols, O R; Eldridge, J J; Baes, M

    2011-01-01

    Massive stars that lose their hydrogen-rich envelope down to a few tenths of a solar mass explode as extended type IIb supernovae, an intriguing subtype that links the hydrogen-rich type II supernovae with the hydrogen-poor type Ib and Ic. The progenitors may be very massive single stars that lose their envelope due to their stellar wind, but mass stripping due to interaction with a companion star in a binary system is currently considered to be the dominant formation channel. We computed an extensive grid of binary models with the Eggleton binary evolution code. The predicted rate from our standard models, which assume conservative mass transfer, is about 6 times smaller than the current rate indicated by observations. It is larger but still comparable to the rate expected from single stars. To recover the observed rate we must generously allow for uncertainties and low accretion efficiencies in combination with limited angular momentum loss from the system. Motivated by the claims of detection and non-detec...

  15. The Evolution of Relativistic Binary Progenitor Systems

    CERN Document Server

    Francischelli, G J; Brown, G E

    2001-01-01

    Relativistic binary pulsars, such as B1534+12 and B1913+16 are characterized by having close orbits with a binary separation of ~ 3 R_\\sun. The progenitor of such a system is a neutron star, helium star binary. The helium star, with a strong stellar wind, is able to spin up its compact companion via accretion. The neutron star's magnetic field is then lowered to observed values of about 10^{10} Gauss. As the pulsar lifetime is inversely proportional to its magnetic field, the possibility of observing such a system is, thus, enhanced by this type of evolution. We will show that a nascent (Crab-like) pulsar in such a system can, through accretion-braking torques (i.e. the "propeller effect") and wind-induced spin-up rates, reach equilibrium periods that are close to observed values. Such processes occur within the relatively short helium star lifetimes. Additionally, we find that the final outcome of such evolutionary scenarios depends strongly on initial parameters, particularly the initial binary separation a...

  16. Subretinal transplantation of mouse retinal progenitor cells

    Institute of Scientific and Technical Information of China (English)

    Caihui Jiang; Maonian Zhang; Henry Klassen; Michael Young

    2011-01-01

    The development of cell replacement techniques is promising as a potential treatment for photoreceptor loss. However, the limited integration ability of donor and recipient cells presents a challenge following transplantation. In the present study, retinal progenitor cells (RPCs) were harvested from the neural retinas of enhanced green fluorescent protein mice on postnatal day 1, and expanded in a neurobasal medium supplemented with fetal bovine serum without endothelial growth factor. Using a confocal microscope, immunohistochemistry demonstrated that expanded RPCs in vitro maintain retinal stem cell properties and can be differentiated into photoreceptor cells. Three weeks after transplantation, subretinal transplanted RPCs were found to have migrated and integrated into the outer nuclear layer of recipient retinas with laser injury, some of the integrated cells had differentiated into photoreceptors, and a subpopulation of these cells expressed photoreceptor specific synaptic protein, appearing to form synaptic connections with bipolar cells. These results suggest that subretinal transplantation of RPCs may provide a feasible therapeutic strategy for the loss of retinal photoreceptor cells.

  17. Type Ia Supernovae: Colors, Rates, and Progenitors

    CERN Document Server

    Heringer, Epson; Kezwer, Jason; Graham, Melissa L; Sand, David; Bildfell, Chris

    2016-01-01

    The rate of type Ia supernovae (SNe Ia) in a galaxy depends not only on stellar mass, but also on star formation history. Here we show that two simple observational quantities ($g-r$ or $u-r$ host galaxy color, and $r$-band luminosity), coupled with an assumed delay time distribution (the rate of SNe Ia as a function of time for an instantaneous burst of star formation), are sufficient to accurately determine a galaxy's SN Ia rate, with very little sensitivity to the precise details of the star formation history. Using this result, we compare observed and predicted color distributions of SN Ia hosts for the MENeaCS cluster supernova survey, and for the SDSS Stripe 82 supernova survey. The observations are consistent with a continuous delay time distribution (DTD), without any cutoff. For old progenitor systems the power-law slope for the DTD is found to be $-1.50 ^{+0.19} _{-0.15}$. This result favours the double degenerate scenario for SN Ia, though other interpretations are possible. We find that the late-t...

  18. Hepatic progenitors for liver disease: current position

    Directory of Open Access Journals (Sweden)

    Alice Conigliaro

    2010-02-01

    Full Text Available Alice Conigliaro1, David A Brenner2, Tatiana Kisseleva21University “La Sapienza”, Dipartimento di Biotecnologie Cellulari ed Ematologia Policlinico Umberto I, V Clinica Medica, Rome, Italy; 2Department of Medicine, University of California, San Diego, La Jolla, CA, USAAbstract: Liver regeneration restores the original functionality of hepatocytes and cholangiocytes in response to injury. It is regulated on several levels, with different cellular populations contributing to this process, eg, hepatocytes, liver precursor cells, intrahepatic stem cells. In response to injury, mature hepatocytes have the capability to proliferate and give rise to new hepatocytes and cholangiocytes. Meanwhile, liver precursor cells (oval cells have become the most recognized bipotential precursor cells in the damaged liver. They rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis. There is a growing body of evidence that oval cells originate from the intrahepatic stem cell(s, which in turn give(s rise to epithelial, including oval cells, and/or other hepatic cells of nonepithelial origin. Since there is a close relationship between the liver and hematopoiesis, bone marrow derived cells can also contribute to liver regeneration by the fusion of myeloid cells with damaged hepatocytes, or differentiation of mesenchymal stem cells into hepatocyte-like cells. The current review discusses the contribution of different cells to liver regeneration and their characteristics.Keywords: hepatic progenitor, liver disease, liver precursor cells, oval cells, hepatocytes, intrahepatic stem cells, cholangiocytes

  19. Effect of AGM and fetal liver-derived stromal cell lines on globin expression in adult baboon (P. anubis bone marrow-derived erythroid progenitors.

    Directory of Open Access Journals (Sweden)

    Donald Lavelle

    Full Text Available This study was performed to investigate the hypothesis that the erythroid micro-environment plays a role in regulation of globin gene expression during adult erythroid differentiation. Adult baboon bone marrow and human cord blood CD34+ progenitors were grown in methylcellulose, liquid media, and in co-culture with stromal cell lines derived from different developmental stages in identical media supporting erythroid differentiation to examine the effect of the micro-environment on globin gene expression. Adult progenitors express high levels of γ-globin in liquid and methylcellulose media but low, physiological levels in stromal cell co-cultures. In contrast, γ-globin expression remained high in cord blood progenitors in stromal cell line co-cultures. Differences in γ-globin gene expression between adult progenitors in stromal cell line co-cultures and liquid media required cell-cell contact and were associated with differences in rate of differentiation and γ-globin promoter DNA methylation. We conclude that γ-globin expression in adult-derived erythroid cells can be influenced by the micro-environment, suggesting new potential targets for HbF induction.

  20. Circulating Hematopoietic Stem and Progenitor Cells in Aging Atomic Bomb Survivors.

    Science.gov (United States)

    Kyoizumi, Seishi; Kubo, Yoshiko; Misumi, Munechika; Kajimura, Junko; Yoshida, Kengo; Hayashi, Tomonori; Imai, Kazue; Ohishi, Waka; Nakachi, Kei; Young, Lauren F; Shieh, Jae-Hung; Moore, Malcolm A; van den Brink, Marcel R M; Kusunoki, Yoichiro

    2016-01-01

    It is not yet known whether hematopoietic stem and progenitor cells (HSPCs) are compromised in the aging population of atomic bomb (A-bomb) survivors after their exposure nearly 70 years ago. To address this, we evaluated age- and radiation-related changes in different subtypes of circulating HSPCs among the CD34-positive/lineage marker-negative (CD34(+)Lin(-)) cell population in 231 Hiroshima A-bomb survivors. We enumerated functional HSPC subtypes, including: cobblestone area-forming cells; long-term culture-initiating cells; erythroid burst-forming units; granulocyte and macrophage colony-forming units; and T-cell and natural killer cell progenitors using cell culture. We obtained the count of each HSPC subtype per unit volume of blood and the proportion of each HSPC subtype in CD34(+)Lin(-) cells to represent the lineage commitment trend. Multivariate analyses, using sex, age and radiation dose as variables, showed significantly decreased counts with age in the total CD34(+)Lin(-) cell population and all HSPC subtypes. As for the proportion, only T-cell progenitors decreased significantly with age, suggesting that the commitment to the T-cell lineage in HSPCs continuously declines with age throughout the lifetime. However, neither the CD34(+)Lin(-) cell population, nor HSPC subtypes showed significant radiation-induced dose-dependent changes in counts or proportions. Moreover, the correlations of the proportions among HSPC subtypes in the survivors properly revealed the hierarchy of lineage commitments. Taken together, our findings suggest that many years after exposure to radiation and with advancing age, the number and function of HSPCs in living survivors as a whole may have recovered to normal levels. PMID:26720799

  1. Characterization of Cardiac-Resident Progenitor Cells Expressing High Aldehyde Dehydrogenase Activity

    Directory of Open Access Journals (Sweden)

    Marc-Estienne Roehrich

    2013-01-01

    Full Text Available High aldehyde dehydrogenase (ALDH activity has been associated with stem and progenitor cells in various tissues. Human cord blood and bone marrow ALDH-bright (ALDHbr cells have displayed angiogenic activity in preclinical studies and have been shown to be safe in clinical trials in patients with ischemic cardiovascular disease. The presence of ALDHbr cells in the heart has not been evaluated so far. We have characterized ALDHbr cells isolated from mouse hearts. One percent of nonmyocytic cells from neonatal and adult hearts were ALDHbr. ALDHvery-br cells were more frequent in neonatal hearts than adult. ALDHbr cells were more frequent in atria than ventricles. Expression of ALDH1A1 isozyme transcripts was highest in ALDHvery-br cells, intermediate in ALDHbr cells, and lowest in ALDHdim cells. ALDH1A2 expression was highest in ALDHvery-br cells, intermediate in ALDHdim cells, and lowest in ALDHbr cells. ALDH1A3 and ALDH2 expression was detectable in ALDHvery-br and ALDHbr cells, unlike ALDHdim cells, albeit at lower levels compared with ALDH1A1 and ALDH1A2. Freshly isolated ALDHbr cells were enriched for cells expressing stem cell antigen-1, CD34, CD90, CD44, and CD106. ALDHbr cells, unlike ALDHdim cells, could be grown in culture for more than 40 passages. They expressed sarcomeric α-actinin and could be differentiated along multiple mesenchymal lineages. However, the proportion of ALDHbr cells declined with cell passage. In conclusion, the cardiac-derived ALDHbr population is enriched for progenitor cells that exhibit mesenchymal progenitor-like characteristics and can be expanded in culture. The regenerative potential of cardiac-derived ALDHbr cells remains to be evaluated.

  2. Cord Blood

    Directory of Open Access Journals (Sweden)

    Saeed Abroun

    2014-05-01

    Full Text Available   Stem cells are naïve or master cells. This means they can transform into special 200 cell types as needed by body, and each of these cells has just one function. Stem cells are found in many parts of the human body, although some sources have richer concentrations than others. Some excellent sources of stem cells, such as bone marrow, peripheral blood, cord blood, other tissue stem cells and human embryos, which last one are controversial and their use can be illegal in some countries. Cord blood is a sample of blood taken from a newborn baby's umbilical cord. It is a rich source of stem cells, umbilical cord blood and tissue are collected from material that normally has no use following a child’s birth. Umbilical cord blood and tissue cells are rich sources of stem cells, which have been used in the treatment of over 80 diseases including leukemia, lymphoma and anemia as bone marrow stem cell potency.  The most common disease category has been leukemia. The next largest group is inherited diseases. Patients with lymphoma, myelodysplasia and severe aplastic anemia have also been successfully transplanted with cord blood. Cord blood is obtained by syringing out the placenta through the umbilical cord at the time of childbirth, after the cord has been detached from the newborn. Collecting stem cells from umbilical blood and tissue is ethical, pain-free, safe and simple. When they are needed to treat your child later in life, there will be no rejection or incompatibility issues, as the procedure will be using their own cells. In contrast, stem cells from donors do have these potential problems. By consider about cord blood potency, cord blood banks (familial or public were established. In IRAN, four cord blood banks has activity, Shariati BMT center cord blood bank, Royan familial cord blood banks, Royan public cord blood banks and Iranian Blood Transfusion Organ cord blood banks. Despite 50,000 sample which storage in these banks, but the

  3. Effects of CPA Loading Temperature and Removal Protocols on MNC Vitrification

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 Introduction Anogeneic bone marrow transplantation is used for the treatment of a variety of malignant and nonmalignant hematological disorders. Human umbilical cord blood is another source of hematopoietic stem cells. It is accepted that there are definite advantages in the use of cord blood (CB) as a source of haematopoietic progenitor cells (HPC) in selected patients with malignant and non-malignant haematological conditions. Most current protocols for CB cryopreservation use the traditional slow cooli...

  4. Macrophage-Mediated Lymphangiogenesis: The Emerging Role of Macrophages as Lymphatic Endothelial Progenitors

    Energy Technology Data Exchange (ETDEWEB)

    Ran, Sophia, E-mail: sran@siumed.edu; Montgomery, Kyle E. [Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, 801 N. Rutledge, Springfield, IL 62794 (United States)

    2012-06-27

    It is widely accepted that macrophages and other inflammatory cells support tumor progression and metastasis. During early stages of neoplastic development, tumor-infiltrating macrophages (TAMs) mount an immune response against transformed cells. Frequently, however, cancer cells escape the immune surveillance, an event that is accompanied by macrophage transition from an anti-tumor to a pro-tumorigenic type. The latter is characterized by high expression of factors that activate endothelial cells, suppress immune response, degrade extracellular matrix, and promote tumor growth. Cumulatively, these products of TAMs promote tumor expansion and growth of both blood and lymphatic vessels that facilitate metastatic spread. Breast cancers and other epithelial malignancies induce the formation of new lymphatic vessels (i.e., lymphangiogenesis) that leads to lymphatic and subsequently, to distant metastasis. Both experimental and clinical studies have shown that TAMs significantly promote tumor lymphangiogenesis through paracrine and cell autonomous modes. The paracrine effect consists of the expression of a variety of pro-lymphangiogenic factors that activate the preexisting lymphatic vessels. The evidence for cell-autonomous contribution is based on the observed tumor mobilization of macrophage-derived lymphatic endothelial cell progenitors (M-LECP) that integrate into lymphatic vessels prior to sprouting. This review will summarize the current knowledge of macrophage-dependent growth of new lymphatic vessels with specific emphasis on an emerging role of macrophages as lymphatic endothelial cell progenitors (M-LECP)

  5. The impact of juvenile coxsackievirus infection on cardiac progenitor cells and postnatal heart development.

    Science.gov (United States)

    Sin, Jon; Puccini, Jenna M; Huang, Chengqun; Konstandin, Mathias H; Gilbert, Paul E; Sussman, Mark A; Gottlieb, Roberta A; Feuer, Ralph

    2014-07-01

    Coxsackievirus B (CVB) is an enterovirus that most commonly causes a self-limited febrile illness in infants, but cases of severe infection can manifest in acute myocarditis. Chronic consequences of mild CVB infection are unknown, though there is an epidemiologic association between early subclinical infections and late heart failure, raising the possibility of subtle damage leading to late-onset dysfunction, or chronic ongoing injury due to inflammatory reactions during latent infection. Here we describe a mouse model of juvenile infection with a subclinical dose of coxsackievirus B3 (CVB3) which showed no evident symptoms, either immediately following infection or in adult mice. However following physiological or pharmacologically-induced cardiac stress, juvenile-infected adult mice underwent cardiac hypertrophy and dilation indicative of progression to heart failure. Evaluation of the vasculature in the hearts of adult mice subjected to cardiac stress showed a compensatory increase in CD31+ blood vessel formation, although this effect was suppressed in juvenile-infected mice. Moreover, CVB3 efficiently infected juvenile c-kit+ cells, and cardiac progenitor cell numbers were reduced in the hearts of juvenile-infected adult mice. These results suggest that the exhausted cardiac progenitor cell pool following juvenile CVB3 infection may impair the heart's ability to increase capillary density to adapt to increased load.

  6. Constitutive expression of pluripotency-associated genes in mesodermal progenitor cells (MPCs.

    Directory of Open Access Journals (Sweden)

    Simone Pacini

    Full Text Available BACKGROUND: We recently characterized a progenitor of mesodermal lineage (MPCs from the human bone marrow of adults or umbilical cord blood. These cells are progenitors able to differentiate toward mesenchymal, endothelial and cardiomyogenic lineages. Here we present an extensive molecular characterization of MPCs, from bone marrow samples, including 39 genes involved in stem cell machinery, differentiation and cell cycle regulation. METHODOLOGY/PRINCIPAL FINDINGS: MPCs are cytofluorimetrically characterized and quantitative RT-PCR was performed to evaluate the gene expression profile, comparing it with MSCs and hESCs lines. Immunofluorescence and dot-blot analysis confirm qRT-PCR data. MPCs exhibit an increased expression of OCT4, NANOG, SALL4, FBX15, SPP1 and to a lesser extent c-MYC and KLF4, but lack LIN28 and SOX2. MPCs highly express SOX15. CONCLUSIONS/SIGNIFICANCE: MPCs express many pluripotency-associated genes and show a peculiar Oct-4 molecular circuit. Understanding this unique molecular mechanism could lead to identifying MPCs as feasible, long telomeres, target cells for reprogramming with no up-regulation of the p53 pathway. Furthermore MPCs are easily and inexpensively harvested from human bone marrow.

  7. Constitutive Expression of Pluripotency-Associated Genes in Mesodermal Progenitor Cells (MPCs)

    Science.gov (United States)

    Pacini, Simone; Carnicelli, Vittoria; Trombi, Luisa; Montali, Marina; Fazzi, Rita; Lazzarini, Edoardo; Giannotti, Stefano; Petrini, Mario

    2010-01-01

    Background We recently characterized a progenitor of mesodermal lineage (MPCs) from the human bone marrow of adults or umbilical cord blood. These cells are progenitors able to differentiate toward mesenchymal, endothelial and cardiomyogenic lineages. Here we present an extensive molecular characterization of MPCs, from bone marrow samples, including 39 genes involved in stem cell machinery, differentiation and cell cycle regulation. Methodology/Principal Findings MPCs are cytofluorimetrically characterized and quantitative RT-PCR was performed to evaluate the gene expression profile, comparing it with MSCs and hESCs lines. Immunofluorescence and dot-blot analysis confirm qRT-PCR data. MPCs exhibit an increased expression of OCT4, NANOG, SALL4, FBX15, SPP1 and to a lesser extent c-MYC and KLF4, but lack LIN28 and SOX2. MPCs highly express SOX15. Conclusions/Significance MPCs express many pluripotency-associated genes and show a peculiar Oct-4 molecular circuit. Understanding this unique molecular mechanism could lead to identifying MPCs as feasible, long telomeres, target cells for reprogramming with no up-regulation of the p53 pathway. Furthermore MPCs are easily and inexpensively harvested from human bone marrow. PMID:20360837

  8. Deficit of circulating stem – progenitor cells in opiate addiction: a pilot study

    Directory of Open Access Journals (Sweden)

    Davidson Peter

    2007-07-01

    Full Text Available Abstract A substantial literature describes the capacity of all addictive drugs to slow cell growth and potentiate apoptosis. Flow cytometry was used as a means to compare two lineages of circulating progenitor cells in addicted patients. Buprenorphine treated opiate addicts were compared with medical patients. Peripheral venous blood CD34+ CD45+ double positive cells were counted as haemopoietic stem cells (HSC's, and CD34+ KDR+ (VEGFR2+ cells were taken as endothelial progenitor cells (EPC's. 10 opiate dependent patients with substance use disorder (SUD and 11 non-addicted (N-SUD were studied. The ages were (mean + S.D. 36.2 + 8.6 and 56.4 + 18.6 respectively (P 0.15, OR = 0.09, 95% C.I. 0.01–0.97, a finding of some interest given the substantially older age of the N-SUD group. These laboratory data are thus consistent with clinical data suggesting accelerated ageing in addicted humans and implicate the important stem cell pool in both addiction toxicology and ageing. They carry important policy implications for understanding the fundamental toxicology of addiction, and suggest that the toxicity both of addiction itself and of indefinite agonist maintenance therapies may have been seriously underestimated.

  9. Chief sources of brachiopod recovery from the end Ordovician mass extinction with special references to progenitors

    Institute of Scientific and Technical Information of China (English)

    戎嘉余; 詹仁斌

    1999-01-01

    Survivor, Lazarus and progenitor taxa are sources of biotic recovery following mass extinction. Investigations of the benthic brachiopods through the latest Ordovician mass extinction shows that progenitors developed many evolutionary novelties and successful surviving mechanisms. They are superior to survivors and Lazarus taxa in their ability to adapt to environmental changes. They are the primary source of macroevolution and the ancestors of a number of new taxa. Three kinds of progenitors are recognized based on the Ordovician-Silurian brachiopods from South China: survivor-progenitors, crisis-progenitors and Lazarus-progenitors; the last has the strongest ability to resist adverse environments, and is the most diverse and abundant.

  10. Blood / Money

    OpenAIRE

    Strong, Thomas

    1997-01-01

    Marilyn Strathern has argued that "nature" in Euro-American culture has appeared as constraint; it has figured the givens of existence on which human artifice is seen to construct "society" or "culture."(5) Among those givens is the notion that human beings are naturally individuals. And blood, too, images individuality: "The very thought of blood, individual blood, touches the deepest feelings in man about life and death" ([RIchard Titmuss] 16.) Transfusion medicine, then, draws on a series ...

  11. On the Progenitor of the Type IIb Supernova 2016gkg

    CERN Document Server

    Kilpatrick, Charles D; Abramson, Louis E; Pan, Yen-Chen; Lu, Cicero-Xinyu; Williams, Peter; Treu, Tommaso; Siebert, Matthew R; Fassnacht, Christopher D; Max, Claire E

    2016-01-01

    We present a detection in pre-explosion Hubble Space Telescope (HST) imaging of a point source consistent with being the progenitor star of the Type IIb supernova (SN IIb) 2016gkg. Post-explosion imaging from the Keck Adaptive Optics system was used to perform relative astrometry between the Keck and HST imaging. We identify a single point source in the HST images coincident with the SN position to 0.89-sigma. The HST photometry is consistent with the progenitor star being an A0Ia star with T=9500 K and log (L/Lsun)=5.15. We find that the SN 2016gkg progenitor star appears more consistent with binary than single-star evolutionary models. In addition, early-time light curve data from SN 2016gkg revealed a rapid rise in luminosity within ~0.4 days of non-detection limits, consistent with models of the cooling phase after shock break-out. We use these data to determine an explosion date of 20.15 September 2016 and progenitor star radius of log (R/Rsun)=2.41, which agrees with photometry from the progenitor star....

  12. Impaired DNA replication within progenitor cell pools promotes leukemogenesis.

    Directory of Open Access Journals (Sweden)

    Ganna Bilousova

    2005-12-01

    Full Text Available Impaired cell cycle progression can be paradoxically associated with increased rates of malignancies. Using retroviral transduction of bone marrow progenitors followed by transplantation into mice, we demonstrate that inhibition of hematopoietic progenitor cell proliferation impairs competition, promoting the expansion of progenitors that acquire oncogenic mutations which restore cell cycle progression. Conditions that impair DNA replication dramatically enhance the proliferative advantage provided by the expression of Bcr-Abl or mutant p53, which provide no apparent competitive advantage under conditions of healthy replication. Furthermore, for the Bcr-Abl oncogene the competitive advantage in contexts of impaired DNA replication dramatically increases leukemogenesis. Impaired replication within hematopoietic progenitor cell pools can select for oncogenic events and thereby promote leukemia, demonstrating the importance of replicative competence in the prevention of tumorigenesis. The demonstration that replication-impaired, poorly competitive progenitor cell pools can promote tumorigenesis provides a new rationale for links between tumorigenesis and common human conditions of impaired DNA replication such as dietary folate deficiency, chemotherapeutics targeting dNTP synthesis, and polymorphisms in genes important for DNA metabolism.

  13. Observational Clues to the Progenitors of Type Ia Supernovae

    Science.gov (United States)

    Maoz, Dan; Mannucci, Filippo; Nelemans, Gijs

    2014-08-01

    Type Ia supernovae (SNe Ia) are important distance indicators, element factories, cosmic-ray accelerators, kinetic-energy sources in galaxy evolution, and end points of stellar binary evolution. It has long been clear that a SN Ia must be the runaway thermonuclear explosion of a degenerate carbon-oxygen stellar core, most likely a white dwarf (WD). However, the specific progenitor systems of SNe Ia, and the processes that lead to their ignition, have not been identified. Two broad classes of progenitor binary systems have long been considered: single-degenerate (SD), in which a WD gains mass from a nondegenerate star; and double-degenerate (DD), involving the merger of two WDs. New theoretical work has enriched these possibilities with some interesting updates and variants. We review the significant recent observational progress in addressing the progenitor problem. We consider clues that have emerged from the observed properties of the various proposed progenitor populations, from studies of SN Ia sites—pre- and postexplosion—from analysis of the explosions themselves and from the measurement of event rates. The recent nearby and well-studied event, SN 2011fe, has been particularly revealing. The observational results are not yet conclusive and sometimes prone to competing theoretical interpretations. Nevertheless, it appears that DD progenitors, long considered the underdog option, could be behind some, if not all, SNe Ia. We point to some directions that may lead to future progress.

  14. Optimisation of a quantitative polymerase chain reaction-based strategy for the detection and quantification of human herpesvirus 6 DNA in patients undergoing allogeneic haematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Miriam YH Ueda

    2015-06-01

    Full Text Available Human herpesvirus 6 (HHV-6 may cause severe complications after haematopoietic stem cell transplantation (HSCT. Monitoring this virus and providing precise, rapid and early diagnosis of related clinical diseases, constitute essential measures to improve outcomes. A prospective survey on the incidence and clinical features of HHV-6 infections after HSCT has not yet been conducted in Brazilian patients and the impact of this infection on HSCT outcome remains unclear. A rapid test based on real-time quantitative polymerase chain reaction (qPCR has been optimised to screen and quantify clinical samples for HHV-6. The detection step was based on reaction with TaqMan® hydrolysis probes. A set of previously described primers and probes have been tested to evaluate efficiency, sensitivity and reproducibility. The target efficiency range was 91.4% with linearity ranging from 10-106 copies/reaction and a limit of detection of five copies/reaction or 250 copies/mL of plasma. The qPCR assay developed in the present study was simple, rapid and sensitive, allowing the detection of a wide range of HHV-6 loads. In conclusion, this test may be useful as a practical tool to help elucidate the clinical relevance of HHV-6 infection and reactivation in different scenarios and to determine the need for surveillance.

  15. Susceptibility to an inoculum of infectious hypodermal and haematopoietic necrosis virus (IHHNV) in three batches of whiteleg shrimp Litopenaeusvannamei (Boone, 1931).

    Science.gov (United States)

    Escobedo-Bonilla, César Marcial; Rangel, José Luis Ibarra

    2014-01-01

    The present study evaluated the susceptibility of three different batches of whiteleg shrimp Litopenaeusvannamei from Mexico to an inoculum of infectious hypodermal and haematopoietic necrosis virus (IHHNV). Each of the three shrimp batches came from a different hatchery. Because of their origin, it was possible that the genetic makeup of these batches was different among each other. The three batches tested showed differences in IHHNV susceptibility. Here, susceptibility is defined as the capacity of the host to become infected, and it can be measured by the infectivity titer. Susceptibility to IHHNV was observed in decreasing order in shrimp from batch 1 (hatchery from El Rosario, Sinaloa), batch 3 (hatchery from Nayarit) and batch 2 (hatchery from El Walamo, Sinaloa), respectively. The largest susceptibility difference between batches was 5012 times, and that between early and late juveniles from the same batch was 25 times. These results indicate that within a species, susceptibility to a pathogen such as IHHNV can have large differences. Susceptibility to pathogens is an important trait to consider before performing studies on pathogenesis. It may influence virological parameters such as speed of replication, pathogenicity and virus titer. In order to evaluate the potential use of IHHNV as a natural control agent against white spot syndrome virus (WSSV), it is necessary to know host susceptibility and the kinetics of IHHNV infection. These features can help to determine the conditions in which IHHNV could be used as antagonist in a WSSV infection.

  16. Susceptibility to an inoculum of infectious hypodermal and haematopoietic necrosis virus (IHHNV in three batches of whiteleg shrimp Litopenaeus vannamei (Boone, 1931

    Directory of Open Access Journals (Sweden)

    Cesar Marcial Escobedo-Bonilla

    2014-11-01

    Full Text Available The present study evaluated the susceptibility of three different batches of whiteleg shrimp Litopenaeus vannamei from Mexico to an inoculum of infectious hypodermal and haematopoietic necrosis virus (IHHNV. Each of the three shrimp batches came from a different hatchery. Because of their origin, it was possible that the genetic makeup of these batches was different among each other. The three batches tested showed differences in IHHNV susceptibility. Here, susceptibility is defined as the capacity of the host to become infected, and it can be measured by the infectivity titer. Susceptibility to IHHNV was observed in decreasing order in shrimp from batch 1 (hatchery from El Rosario, Sinaloa, batch 3 (hatchery from Nayarit and batch 2 (hatchery from El Walamo, Sinaloa, respectively. The largest susceptibility difference between batches was 5012 times, and that between early and late juveniles from the same batch was 25 times. These results indicate that within a species, susceptibility to a pathogen such as IHHNV can have large differences. Susceptibility to pathogens is an important trait to consider before performing studies on pathogenesis. It may influence virological parameters such as speed of replication, pathogenicity and virus titer. In order to evaluate the potential use of IHHNV as a natural control agent against white spot syndrome virus (WSSV, it is necessary to know host susceptibility and the kinetics of IHHNV infection. These features can help to determine the conditions in which IHHNV could be used as antagonist in a WSSV infection.

  17. Optimisation of a quantitative polymerase chain reaction-based strategy for the detection and quantification of human herpesvirus 6 DNA in patients undergoing allogeneic haematopoietic stem cell transplantation

    Science.gov (United States)

    Ueda, Miriam YH; Alvarenga, Paulo G; Real, Juliana M; Moreira, Eloisa de Sá; Watanabe, Aripuanã; Passos-Castilho, Ana Maria; Vescovi, Matheus; Novis, Yana; Rocha, Vanderson; Seber, Adriana; Oliveira, Jose SR; Rodrigues, Celso A; Granato, Celso FH

    2015-01-01

    Human herpesvirus 6 (HHV-6) may cause severe complications after haematopoietic stem cell transplantation (HSCT). Monitoring this virus and providing precise, rapid and early diagnosis of related clinical diseases, constitute essential measures to improve outcomes. A prospective survey on the incidence and clinical features of HHV-6 infections after HSCT has not yet been conducted in Brazilian patients and the impact of this infection on HSCT outcome remains unclear. A rapid test based on real-time quantitative polymerase chain reaction (qPCR) has been optimised to screen and quantify clinical samples for HHV-6. The detection step was based on reaction with TaqMan® hydrolysis probes. A set of previously described primers and probes have been tested to evaluate efficiency, sensitivity and reproducibility. The target efficiency range was 91.4% with linearity ranging from 10-106 copies/reaction and a limit of detection of five copies/reaction or 250 copies/mL of plasma. The qPCR assay developed in the present study was simple, rapid and sensitive, allowing the detection of a wide range of HHV-6 loads. In conclusion, this test may be useful as a practical tool to help elucidate the clinical relevance of HHV-6 infection and reactivation in different scenarios and to determine the need for surveillance. PMID:26038958

  18. PlGF repairs myocardial ischemia through mechanisms of angiogenesis, cardioprotection and recruitment of myo-angiogenic competent marrow progenitors.

    Directory of Open Access Journals (Sweden)

    Hiroto Iwasaki

    Full Text Available RATIONALE: Despite preclinical success in regenerating and revascularizing the infarcted heart using angiogenic growth factors or bone marrow (BM cells, recent clinical trials have revealed less benefit from these therapies than expected. OBJECTIVE: We explored the therapeutic potential of myocardial gene therapy of placental growth factor (PlGF, a VEGF-related angiogenic growth factor, with progenitor-mobilizing activity. METHODS AND RESULTS: Myocardial PlGF gene therapy improves cardiac performance after myocardial infarction, by inducing cardiac repair and reparative myoangiogenesis, via upregulation of paracrine anti-apoptotic and angiogenic factors. In addition, PlGF therapy stimulated Sca-1(+/Lin(- (SL BM progenitor proliferation, enhanced their mobilization into peripheral blood, and promoted their recruitment into the peri-infarct borders. Moreover, PlGF enhanced endothelial progenitor colony formation of BM-derived SL cells, and induced a phenotypic switch of BM-SL cells, recruited in the infarct, to the endothelial, smooth muscle and cardiomyocyte lineage. CONCLUSIONS: Such pleiotropic effects of PlGF on cardiac repair and regeneration offer novel opportunities in the treatment of ischemic heart disease.

  19. OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Xiaoli Chen

    2015-09-01

    Full Text Available Generating engraftable hematopoietic stem cells (HSCs from pluripotent stem cells (PSCs is an ideal approach for obtaining induced HSCs for cell therapy. However, the path from PSCs to robustly induced HSCs (iHSCs in vitro remains elusive. We hypothesize that the modification of hematopoietic niche cells by transcription factors facilitates the derivation of induced HSCs from PSCs. The Lhx2 transcription factor is expressed in fetal liver stromal cells but not in fetal blood cells. Knocking out Lhx2 leads to a fetal hematopoietic defect in a cell non-autonomous role. In this study, we demonstrate that the ectopic expression of Lhx2 in OP9 cells (OP9-Lhx2 accelerates the hematopoietic differentiation of PSCs. OP9-Lhx2 significantly increased the yields of hematopoietic progenitor cells via co-culture with PSCs in vitro. Interestingly, the co-injection of OP9-Lhx2 and PSCs into immune deficient mice also increased the proportion of hematopoietic progenitors via the formation of teratomas. The transplantation of phenotypic HSCs from OP9-Lhx2 teratomas but not from the OP9 control supported a transient repopulating capability. The upregulation of Apln gene by Lhx2 is correlated to the hematopoietic commitment property of OP9-Lhx2. Furthermore, the enforced expression of Apln in OP9 cells significantly increased the hematopoietic differentiation of PSCs. These results indicate that OP9-Lhx2 is a good cell line for regeneration of hematopoietic progenitors both in vitro and in vivo.

  20. Moderate Hypoxia Exhibits Increased Endothelial Progenitor Vessel-forming Ability However Gestational Diabetes Caused to Impede Compensatory Defense Reaction.

    Science.gov (United States)

    Dincer, U Deniz

    2016-05-30

    Endothelium represents a defense barrier and responds and integrates neuro humoral stimulus which describes as a compensatory mechanism. Endothelium formed with endothelial cells (ECs) and their progenitors. Endothelial progenitor cells (EPCs) represent minor subpopulation of mononuclear cells in the blood. During acute hypoxia, larger amount of EPCs mobilize into the peripheral blood and they directly contribute revascularization process. One of the subtypes of EPC is termed endothelial colony forming cells (ECFCs) which they possess de novo vessel-forming ability. The present study aims to investigate the role of hypoxia in EPCs functional and vessel-forming ability. Furthermore, it was investigated whether fetal exposure to a diabetic intrauterine environment influence EPCs adaptation ability. Human umbilical cord blood (HUCB) derived ECFCs were selected in all experimental procedures obtained from normal and gestational diabetes mellitus (GDM) subjects via in vitro cell culture methods. Early passage (assay conducted onto HUCB ECFCs to investigate their functional clonogenic ability. To quantify their vessel forming ability matrigel assay was applied. These data demonstrates that moderate hypoxia results increased vessel-forming ability and VEGFA expression in HUCB ECFCs obtained from control subjects. However, GDM caused to impede compensatory defense reaction against hypoxia which observed in control subjects. Thus, it illuminates beneficial information related future therapeutic modalities. PMID:27426097

  1. Moderate Hypoxia Exhibits Increased Endothelial Progenitor Vessel-forming Ability However Gestational Diabetes Caused to Impede Compensatory Defense Reaction

    Science.gov (United States)

    Dincer, U. Deniz

    2016-01-01

    Endothelium represents a defense barrier and responds and integrates neuro humoral stimulus which describes as a compensatory mechanism. Endothelium formed with endothelial cells (ECs) and their progenitors. Endothelial progenitor cells (EPCs) represent minor subpopulation of mononuclear cells in the blood. During acute hypoxia, larger amount of EPCs mobilize into the peripheral blood and they directly contribute revascularization process. One of the subtypes of EPC is termed endothelial colony forming cells (ECFCs) which they possess de novo vessel-forming ability. The present study aims to investigate the role of hypoxia in EPCs functional and vessel-forming ability. Furthermore, it was investigated whether fetal exposure to a diabetic intrauterine environment influence EPCs adaptation ability. Human umbilical cord blood (HUCB) derived ECFCs were selected in all experimental procedures obtained from normal and gestational diabetes mellitus (GDM) subjects via in vitro cell culture methods. Early passage (hypoxia associated gene specific primers designed to perform Real-time PCR. Senescenes assay conducted onto HUCB ECFCs to investigate their functional clonogenic ability. To quantify their vessel forming ability matrigel assay was applied. These data demonstrates that moderate hypoxia results increased vessel-forming ability and VEGFA expression in HUCB ECFCs obtained from control subjects. However, GDM caused to impede compensatory defense reaction against hypoxia which observed in control subjects. Thus, it illuminates beneficial information related future therapeutic modalities. PMID:27426097

  2. Understanding Blood Counts

    Science.gov (United States)

    ... Lab and Imaging Tests Understanding Blood Counts Understanding Blood Counts Understanding Blood Counts SHARE: Print Glossary Blood cell counts give ... your blood that's occupied by red cells. Normal Blood Counts Normal blood counts fall within a range ...

  3. Progenitor Cell Therapy in a Porcine Acute Myocardial Infarction Model Induces Cardiac Hypertrophy, Mediated by Paracrine Secretion of Cardiotrophic Factors Including TGFβ1

    OpenAIRE

    Doyle, Brendan; Sorajja, Paul; Hynes, Brian; Kumar, Arun H. S.; Araoz, Phillip A.; Stalboerger, Paul G.; Miller, Dylan; Reed, Cynthia; Schmeckpeper, Jeffrey; Wang, Shaohua; Liu, Chunsheng; Terzic, Andre; Kruger, David; Riederer, Stephen; Caplice, Noel M.

    2008-01-01

    Administration of endothelial progenitor cells (EPC) is a promising therapy for post-infarction cardiac repair. However, the mechanisms that underlie apparent beneficial effects on myocardial remodeling are unclear. In a porcine model of acute myocardial infarction, we investigated the therapeutic effects of a mixed population of culture modified peripheral blood mononuclear cells (termed hereafter porcine EPC). Porcine EPC were isolated using methods identical to those previously adopted for...

  4. Brain Barriers and a Subpopulation of Astroglial Progenitors of Developing Human Forebrain Are Immunostained for the Glycoprotein YKL-40

    DEFF Research Database (Denmark)

    Bjørnbak, Camilla; Brøchner, Christian B; Larsen, Lars A;

    2014-01-01

    . Immunoreactivity was detected in neuroepithelial cells, radial glial end feet, leptomeningeal cells and choroid plexus epithelial cells. The subpial marginal zone was YKL-40-positive, particularly in the hippocampus, from an early beginning stage in its development. Blood vessels in the intermediate...... in controlling local angiogenesis and access of peripheral cells to the forebrain via secretion from leptomeningeal cells, choroid plexus epithelium and pericytes. Furthermore, we suggest that the small, rounded, YKL-40-positive cells represent a subpopulation of astroglial progenitors, and that YKL-40 could...

  5. Rates and progenitors of type Ia supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Wood-Vasey, William Michael [Univ. of California, Berkeley, CA (United States)

    2004-01-01

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ~ 0.01-0.1 of rV = 4.26$+1.39 +0.10\\atop{-1.93 -0.10}$h3 x 10-4 SNe Ia/yr/Mpc3 from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae.

  6. Rates and progenitors of type Ia supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Wood-Vasey, William Michael

    2004-08-16

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z {approx} 0.01-0.1 of r{sub V} = 4.26{sub -1.93 -0.10}{sup +1.39 +0.10} h{sup 3} x 10{sup -4} SNe Ia/yr/Mpc{sup 3} from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae.

  7. Rates and progenitors of type Ia supernovae

    International Nuclear Information System (INIS)

    analyzing the true sensitivity of a multi-epoch supernova search and finds a Type Ia supernova rate from z ∼ 0.01-0.1 of rV = 4.26-1.93-0.10+1.39+0.10 h3 x 10-4 SNe Ia/yr/Mpc3 from a preliminary analysis of a subsample of the SNfactory prototype search. Several unusual supernovae were found in the course of the SNfactory prototype search. One in particular, SN 2002ic, was the first SN Ia to exhibit convincing evidence for a circumstellar medium and offers valuable insight into the progenitors of Type Ia supernovae

  8. Interleukin-3 and granulocyte-macrophage colony-stimulating factor levels of cord blood plasma in term neonates

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ AIM: Umbilical cord blood plasma contain higher hematopoietic stimulatory activities than adult peripheral blood plasma. IL-3 is regarded as multilineage hematopoietic growth factor that acts on primitive pluripotential stem cells and progenitor cells of every lineage except T and B-lymphoid lineage.

  9. Blood donation

    CERN Multimedia

    GS Department

    2009-01-01

    A blood donation is organised by the Cantonal Hospital of Geneva On Thursday 19 March 2009 from 9 a.m. to 5 p.m. CERN RESTAURANT 2 Number of donations during the last blood donations :135 donors in July 2008 122 donors in November 2008 Let’s do better in 2009 !!! Give 30 minutes of your time to save lives...

  10. BLOOD DONATION

    CERN Document Server

    SC Unit

    2008-01-01

    A blood donation, organized by EFS (Etablissement Français du Sang) of Annemasse will take place On Wednesday 12 November 2008, from 8:30 to 16:00, at CERN Restaurant 2 If possible, please, bring your blood group Card.

  11. Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate

    Science.gov (United States)

    Grover, Amit; Mancini, Elena; Moore, Susan; Mead, Adam J.; Atkinson, Deborah; Rasmussen, Kasper D.; O’Carroll, Donal; Jacobsen, Sten Eirik W.

    2014-01-01

    The erythroid stress cytokine erythropoietin (Epo) supports the development of committed erythroid progenitors, but its ability to act on upstream, multipotent cells remains to be established. We observe that high systemic levels of Epo reprogram the transcriptomes of multi- and bipotent hematopoietic stem/progenitor cells in vivo. This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells (HSCs) and committed erythroid progenitors, leading to increased erythroid and decreased myeloid HSC output. Epo, therefore, has a lineage instructive role in vivo, through suppression of non-erythroid fate options, demonstrating the ability of a cytokine to systematically bias successive lineage choices in favor of the generation of a specific cell type. PMID:24493804

  12. In vitro pancreas organogenesis from dispersed mouse embryonic progenitors

    DEFF Research Database (Denmark)

    Greggio, Chiara; De Franceschi, Filippo; Figueiredo-Larsen, Evan Manuel;

    2014-01-01

    The pancreas is an essential organ that regulates glucose homeostasis and secretes digestive enzymes. Research on pancreas embryogenesis has led to the development of protocols to produce pancreatic cells from stem cells (1). The whole embryonic organ can be cultured at multiple stages...... expanding progenitors and differentiate into endocrine, acinar and ductal cells and which spontaneously self-organize to resemble the embryonic pancreas. We show here that the in vitro process recapitulates many aspects of natural pancreas development. This culture system is suitable to investigate how...... the efficient expansion of dissociated mouse embryonic pancreatic progenitors. By manipulating the composition of the culture medium it is possible to generate either hollow spheres, mainly composed of pancreatic progenitors expanding in their initial state, or, complex organoids which progress to more mature...

  13. CXCR4 expression in prostate cancer progenitor cells.

    Directory of Open Access Journals (Sweden)

    Anna Dubrovska

    Full Text Available Tumor progenitor cells represent a population of drug-resistant cells that can survive conventional chemotherapy and lead to tumor relapse. However, little is known of the role of tumor progenitors in prostate cancer metastasis. The studies reported herein show that the CXCR4/CXCL12 axis, a key regulator of tumor dissemination, plays a role in the maintenance of prostate cancer stem-like cells. The CXCL4/CXCR12 pathway is activated in the CD44(+/CD133(+ prostate progenitor population and affects differentiation potential, cell adhesion, clonal growth and tumorigenicity. Furthermore, prostate tumor xenograft studies in mice showed that a combination of the CXCR4 receptor antagonist AMD3100, which targets prostate cancer stem-like cells, and the conventional chemotherapeutic drug Taxotere, which targets the bulk tumor, is significantly more effective in eradicating tumors as compared to monotherapy.

  14. A neutron star progenitor for FRBs? Insights from polarisation measurements

    CERN Document Server

    Ravi, Vikram

    2016-01-01

    Fast Radio Bursts (FRBs) are intense, millisecond-duration broadband radio transients, the emission mechanisms of which are not understood. Masui et al. recently presented Green Bank Telescope observations of FRB 110523, which displayed temporal variation of the linear polarisation position angle (PA). This effect is commonly seen in radio pulsars and is attributed to a changing projected magnetic field orientation in the emission region as the star rotates. If a neutron star is the progenitor of this FRB, and the emission mechanism is pulsar-like, we show that the progenitor is either rapidly rotating, or the emission originates from a region of complex magnetic field geometry. The observed PA variation could also be caused by propagation effects within a neutron-star magnetosphere, or by spatially varying magnetic fields if the progenitor lies in a dense, highly magnetised environment. Although we urge caution in generalising results from FRB 110523 to the broader FRB population, our analysis serves as a gu...

  15. Osteocytes serve as a progenitor cell of osteosarcoma.

    Science.gov (United States)

    Sottnik, Joseph L; Campbell, Brittany; Mehra, Rohit; Behbahani-Nejad, Omid; Hall, Christopher L; Keller, Evan T

    2014-08-01

    Osteosarcoma (OSA) is the most common primary bone tumor in humans. However, the cell of origin of OSA is not clearly defined although there is evidence that osteoblasts may serve as OSA progenitors. The role of osteocytes, terminally differentiated osteoblasts, as OSA progenitors has yet to be described. Analysis of patient cDNA from publicly available microarray data revealed that patients with OSA have increased expression of dentin matrix phosphoprotein 1 (DMP1), a marker of osteocytes. Analysis of multiple murine, human, and canine OSA cell lines revealed DMP1 expression. To test the tumorigenic potential of osteocytes, MLO-Y4, a SV-40 immortalized murine osteocyte cell line, was injected into subcutaneous and orthotopic (intratibial) sites of mice. Tumor growth occurred in both locations. Orthotopic MLO-Y4 tumors produced mixed osteoblastic/osteolytic radiographic lesions; a hallmark of OSA. Together, these data demonstrate for the first time that osteocytes can serve as OSA progenitors. PMID:24700678

  16. Gravitational Wave Constraints on the Progenitors of Fast Radio Bursts

    CERN Document Server

    Callister, Thomas; Weinstein, Alan

    2016-01-01

    The nature of fast radio bursts (FRBs) remains enigmatic. Highly energetic radio pulses of millisecond duration, fast radio bursts are observed with dispersion measures consistent with an extragalactic source. A variety of models have been proposed to explain their origin. One popular class of theorized FRB progenitor is the coalescence of compact binaries composed of neutron stars and/or black holes. We demonstrate that measurements made by the LIGO and Virgo gravitational wave observatories can be leveraged to severely constrain the validity of FRB binary coalescence models. Existing measurements rule out binary black holes as FRB progenitors, and results from Advanced LIGO's O1 and O2 observing runs will either confirm or strongly rule out binary neutron star and neutron star-black hole progenitors.

  17. Immortalized neural progenitor cells for CNS gene transfer and repair.

    Science.gov (United States)

    Martínez-Serrano, A; Björklund, A

    1997-11-01

    Immortalized multipotent neural stem and progenitor cells have emerged as a highly convenient source of tissue for genetic manipulation and ex vivo gene transfer to the CNS. Recent studies show that these cells, which can be maintained and genetically transduced as cell lines in culture, can survive, integrate and differentiate into both neurons and glia after transplantation to the intact or damaged brain. Progenitors engineered to secrete trophic factors, or to produce neurotransmitter-related or metabolic enzymes can be made to repopulate diseased or injured brain areas, thus providing a new potential therapeutic tool for the blockade of neurodegenerative processes and reversal of behavioural deficits in animal models of neurodegenerative diseases. With further technical improvements, the use of immortalized neural progenitors may bring us closer to the challenging goal of targeted and effective CNS repair.

  18. A monoclonal antibody reactive with normal and leukemic human myeloid progenitor cells.

    Science.gov (United States)

    Griffin, J D; Linch, D; Sabbath, K; Larcom, P; Schlossman, S F

    1984-01-01

    Anti-MY9 is an IgG2b murine monoclonal antibody selected for reactivity with immature normal human myeloid cells. The MY9 antigen is expressed by blasts, promyelocytes and myelocytes in the bone marrow, and by monocytes in the peripheral blood. Erythrocytes, lymphocytes and platelets are MY9 negative. All myeloid colony-forming cells (CFU-GM), a fraction of erythroid burst-forming cells (BFU-E) and multipotent progenitors (CFU-GEMM) are MY9 positive. This antigen is further expressed by the leukemic cells of a majority of patients with AML and myeloid CML-BC. Leukemic stem cells (leukemic colony-forming cells, L-CFC) from most patients tested were also MY9 positive. In contrast, MY9 was not detected on lymphocytic leukemias. Anti-MY9 may be a valuable reagent for the purification of hematopoietic colony-forming cells and for the diagnosis of myeloid-lineage leukemias.

  19. Tainted blood

    DEFF Research Database (Denmark)

    Deleuran, Ida; Sheikh, Zainab Afshan; Hoeyer, Klaus

    2015-01-01

    study of the historical rise and current workings of safety practices in the Danish blood system. Here, we identify a strong focus on contamination in order to avoid 'tainted blood', at the expense of working with risks that could be avoided through enhanced blood monitoring practices. Of further...... significance to this focus are the social dynamics found at the heart of safety practices aimed at avoiding contamination. We argue that such dynamics need more attention, in order to achieve good health outcomes in transfusion medicine. Thus, we conclude that, to ensure continuously safe blood systems, we...... need to move beyond the bifurcation of the social and medical aspects of blood supply as two separate issues and approach social dynamics as key medical safety questions....

  20. Endothelial progenitor cells display clonal restriction in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Dai Kezhi

    2006-06-01

    Full Text Available Abstract Background In multiple myeloma (MM, increased neoangiogenesis contributes to tumor growth and disease progression. Increased levels of endothelial progenitor cells (EPCs contribute to neoangiogenesis in MM, and, importantly, covary with disease activity and response to treatment. In order to understand the mechanisms responsible for increased EPC levels and neoangiogenic function in MM, we investigated whether these cells were clonal by determining X-chromosome inactivation (XCI patterns in female patients by a human androgen receptor assay (HUMARA. In addition, EPCs and bone marrow cells were studied for the presence of clonotypic immunoglobulin heavy-chain (IGH gene rearrangement, which indicates clonality in B cells; thus, its presence in EPCs would indicate a close genetic link between tumor cells in MM and endothelial cells that provide tumor neovascularization. Methods A total of twenty-three consecutive patients who had not received chemotherapy were studied. Screening in 18 patients found that 11 displayed allelic AR in peripheral blood mononuclear cells, and these patients were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2 patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients, EPCs were studied for IGH gene rearrangement using PCR with family-specific primers for IGH variable genes (VH. Results In 11 patients, analysis of EPCs by HUMARA revealed significant skewing (≥ 77% expression of a single allele in 64% (n = 7. In 4 of these patients, XCI skewing was extreme (≥ 90% expression of a single allele. In contrast, XCI in hair root cells was random. Furthermore, PCR amplification with VH primers resulted in amplification of the same product in EPCs and bone marrow cells in 71% (n = 5 of 7 patients, while no IGH rearrangement was found in EPCs from healthy controls. In addition, in patients with XCI skewing in EPCs, advanced age was associated with poorer clinical status

  1. Endothelial progenitors in sepsis: vox clamantis in deserto?

    Science.gov (United States)

    Goligorsky, Michael S

    2011-01-01

    In this issue of Critical Care, Patschan and colleagues present a study of endothelial progenitor cells (EPCs) in patients with sepsis. The importance of this study is in focusing attention on several frequently ignored aspects of sepsis. Among those are the phenomenon of microvascular dysfunction, which is potentially responsible for profound metabolic perturbations at the tissue level, and the role of endothelial progenitors in repair processes. Other important aspects of the study are the regenerative capacity of mobilized EPCs and the dissociation between the numerical value and clonogenic competence. Attempting to restore the competence to EPCs should be a priority in the future. PMID:21489327

  2. Evolutionary Models for Type Ib/c Supernova Progenitors

    OpenAIRE

    Yoon, Sung-Chul

    2015-01-01

    Type Ib/c supernovae (SNe Ib/c) mark the deaths of hydrogen-deficient massive stars. The evolutionary scenarios for SNe Ib/c progenitors involve many important physical processes including mass loss by winds and its metallicity dependence, stellar rotation, and binary interactions. This makes SNe Ib/c an excellent test bed for stellar evolution theory. We review the main results of evolutionary models for SN Ib/c progenitors available in the literature and their confrontation with recent obse...

  3. Cellular plasticity : the good, the bad, and the ugly? Microenvironmental influences on progenitor cell therapy

    NARCIS (Netherlands)

    Moonen, Jan-Renier A. J.; Harmsen, Martin C.; Krenning, Guido

    2012-01-01

    Progenitor cell based therapies have emerged for the treatment of ischemic cardiovascular diseases where there is insufficient endogenous repair. However, clinical success has been limited, which challenges the original premise that transplanted progenitor cells would orchestrate repair. In this rev

  4. Isolation of alveolar epithelial type II progenitor cells from adult human lungs

    OpenAIRE

    Fujino, Naoya; Kubo, Hiroshi; Suzuki, Takaya; Ota, Chiharu; Hegab, Ahmed E.; He, Mei; Suzuki, Satoshi; Suzuki, Takashi; Yamada, Mitsuhiro; Kondo, Takashi; Kato, Hidemasa; Yamaya, Mutsuo

    2010-01-01

    Resident stem/progenitor cells in the lung are important for tissue homeostasis and repair. However, a progenitor population for alveolar type II (ATII) cells in adult human lungs has not been identified. The aim of this study is to isolate progenitor cells from adult human lungs with the ability to differentiate into ATII cells. We isolated colony-forming cells that had the capability for self-renewal and the potential to generate ATII cells in vitro. These undifferentiated progenitor cells ...

  5. Improving engraftment and immune reconstitution in umbilical cord blood transplantation

    Directory of Open Access Journals (Sweden)

    Robert eDanby

    2014-02-01

    Full Text Available Umbilical cord blood (UCB is an important source of haematopoietic stem cells (HSC for allogeneic transplantation when HLA-matched sibling and unrelated donors (MUD are unavailable. Although the overall survival rates of UCB transplantation are comparable to the results with MUD, UCB transplants are associated with slow engraftment, delayed immune reconstitution, and increased opportunistic infections. While this may be a consequence of the lower cell dose in UCB grafts, it also reflects the relative immaturity of cellular immunity within cord blood. Furthermore, the limited number of cells and the non-availability of donor lymphocyte infusions (DLI currently prevent the use of post-transplant cellular immunotherapy to boost donor-derived immunity to treat infection, mixed chimerism and disease relapse. Therefore, to further develop UCB transplantation, many strategies to enhance engraftment and immune reconstitution are currently under investigation. This review summarises our current understanding of engraftment and immune recovery following UCB transplantation and why this differs from allogeneic transplants using other sources of HSC. It also provides an comprehensive overview of the promising techniques being used to improve myeloid and lymphoid recovery, including expansion, homing, and delivery of UCB HSC; combined use of UCB with third party donors; isolation and expansion of NK cells, pathogen specific T cells, and regulatory T cells; methods to protect and/or improve thymopoiesis. As many of these strategies are now in clinical trials, it is anticipated that UCB transplantation will continue to advance, further expanding our understanding of UCB biology and HSC transplantation.

  6. Type Ia supernovae: explosions and progenitors

    Science.gov (United States)

    Kerzendorf, Wolfgang Eitel

    2011-08-01

    that they somehow need to acquire mass if they are to explode as SN Ia. Currently there are two major scenarios for this mass acquisition. In the favoured single degenerate scenario the white dwarf accretes matter from a companion star which is much younger in its evolutionary state. The less favoured double degenerate scenario sees the merger of two white dwarfs (with a total combined mass of more than 1.38 Msun). This thesis has tried to answer the question about the mass acquisition in two ways. First the single degenerate scenario predicts a surviving companion post-explosion. We undertook an observational campaign to find this companion in two ancient supernovae (SN 1572 and SN 1006). Secondly, we have extended an existing code to extract the elemental and energy yields of SNe Ia spectra by automating spectra fitting to specific SNe Ia. This type of analysis, in turn, help diagnose to which of the two major progenitor scenarios is right.

  7. File list: Unc.Oth.05.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.05.AllAg.Multipotent_otic_progenitor mm9 Unclassified Others Multipotent ot...ic progenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.05.AllAg.Multipotent_otic_progenitor.bed ...

  8. File list: DNS.Oth.20.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Oth.20.AllAg.Multipotent_otic_progenitor mm9 DNase-seq Others Multipotent otic ...progenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Oth.20.AllAg.Multipotent_otic_progenitor.bed ...

  9. File list: Unc.Oth.10.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.10.AllAg.Multipotent_otic_progenitor mm9 Unclassified Others Multipotent ot...ic progenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.10.AllAg.Multipotent_otic_progenitor.bed ...

  10. File list: DNS.Oth.50.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Oth.50.AllAg.Multipotent_otic_progenitor mm9 DNase-seq Others Multipotent otic ...progenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Oth.50.AllAg.Multipotent_otic_progenitor.bed ...

  11. File list: Pol.Oth.50.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.50.AllAg.Multipotent_otic_progenitor mm9 RNA polymerase Others Multipotent ...otic progenitor SRX736457,SRX736456 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Oth.50.AllAg.Multipotent_otic_progenitor.bed ...

  12. File list: His.Oth.50.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.50.AllAg.Multipotent_otic_progenitor mm9 Histone Others Multipotent otic pr...ogenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.50.AllAg.Multipotent_otic_progenitor.bed ...

  13. File list: DNS.Oth.10.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Oth.10.AllAg.Multipotent_otic_progenitor mm9 DNase-seq Others Multipotent otic ...progenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Oth.10.AllAg.Multipotent_otic_progenitor.bed ...

  14. File list: Pol.Oth.10.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.10.AllAg.Multipotent_otic_progenitor mm9 RNA polymerase Others Multipotent ...otic progenitor SRX736457,SRX736456 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Oth.10.AllAg.Multipotent_otic_progenitor.bed ...

  15. File list: Pol.Oth.05.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.05.AllAg.Multipotent_otic_progenitor mm9 RNA polymerase Others Multipotent ...otic progenitor SRX736456,SRX736457 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Oth.05.AllAg.Multipotent_otic_progenitor.bed ...

  16. File list: Unc.Oth.50.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.50.AllAg.Multipotent_otic_progenitor mm9 Unclassified Others Multipotent ot...ic progenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.50.AllAg.Multipotent_otic_progenitor.bed ...

  17. File list: Pol.Oth.20.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Oth.20.AllAg.Multipotent_otic_progenitor mm9 RNA polymerase Others Multipotent ...otic progenitor SRX736457,SRX736456 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Oth.20.AllAg.Multipotent_otic_progenitor.bed ...

  18. File list: Oth.Oth.50.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.50.AllAg.Multipotent_otic_progenitor mm9 TFs and others Others Multipotent ...otic progenitor SRX736459,SRX736460,SRX736458,SRX736461 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Oth.50.AllAg.Multipotent_otic_progenitor.bed ...

  19. File list: Unc.Oth.20.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Oth.20.AllAg.Multipotent_otic_progenitor mm9 Unclassified Others Multipotent ot...ic progenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Oth.20.AllAg.Multipotent_otic_progenitor.bed ...

  20. File list: Oth.Oth.20.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.20.AllAg.Multipotent_otic_progenitor mm9 TFs and others Others Multipotent ...otic progenitor SRX736459,SRX736458,SRX736460,SRX736461 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Oth.20.AllAg.Multipotent_otic_progenitor.bed ...

  1. File list: Oth.Oth.10.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.10.AllAg.Multipotent_otic_progenitor mm9 TFs and others Others Multipotent ...otic progenitor SRX736459,SRX736458,SRX736460,SRX736461 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Oth.10.AllAg.Multipotent_otic_progenitor.bed ...

  2. File list: His.Oth.20.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.20.AllAg.Multipotent_otic_progenitor mm9 Histone Others Multipotent otic pr...ogenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.20.AllAg.Multipotent_otic_progenitor.bed ...

  3. File list: DNS.Oth.05.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Oth.05.AllAg.Multipotent_otic_progenitor mm9 DNase-seq Others Multipotent otic ...progenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Oth.05.AllAg.Multipotent_otic_progenitor.bed ...

  4. File list: Oth.Oth.05.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Oth.05.AllAg.Multipotent_otic_progenitor mm9 TFs and others Others Multipotent ...otic progenitor SRX736459,SRX736458,SRX736460,SRX736461 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Oth.05.AllAg.Multipotent_otic_progenitor.bed ...

  5. File list: His.Oth.10.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.10.AllAg.Multipotent_otic_progenitor mm9 Histone Others Multipotent otic pr...ogenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.10.AllAg.Multipotent_otic_progenitor.bed ...

  6. File list: His.Oth.05.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Oth.05.AllAg.Multipotent_otic_progenitor mm9 Histone Others Multipotent otic pr...ogenitor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Oth.05.AllAg.Multipotent_otic_progenitor.bed ...

  7. File list: Pol.Neu.50.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.50.AllAg.Neural_progenitor_cells mm9 RNA polymerase Neural Neural progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.50.AllAg.Neural_progenitor_cells.bed ...

  8. File list: Oth.Neu.10.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.10.AllAg.Neural_progenitor_cells mm9 TFs and others Neural Neural progenito...r cells SRX109472,SRX315274,SRX802060,SRX109471 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.10.AllAg.Neural_progenitor_cells.bed ...

  9. File list: ALL.Neu.50.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.50.AllAg.Neural_progenitor_cells mm9 All antigens Neural Neural progenitor ...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.50.AllAg.Neural_progenitor_cells.bed ...

  10. File list: His.Neu.50.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.50.AllAg.Neural_progenitor_cells mm9 Histone Neural Neural progenitor cells... SRX315278,SRX667383,SRX668241,SRX315276,SRX315277 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.50.AllAg.Neural_progenitor_cells.bed ...

  11. File list: Unc.Neu.10.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.10.AllAg.Induced_neural_progenitors mm9 Unclassified Neural Induced neural ...progenitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.10.AllAg.Induced_neural_progenitors.bed ...

  12. File list: DNS.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Neu.05.AllAg.Induced_neural_progenitors mm9 DNase-seq Neural Induced neural pro...genitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.05.AllAg.Induced_neural_progenitors.bed ...

  13. File list: Unc.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.05.AllAg.Induced_neural_progenitors mm9 Unclassified Neural Induced neural ...progenitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.05.AllAg.Induced_neural_progenitors.bed ...

  14. File list: Pol.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.05.AllAg.Induced_neural_progenitors mm9 RNA polymerase Neural Induced neura...l progenitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.05.AllAg.Induced_neural_progenitors.bed ...

  15. File list: Oth.Neu.50.AllAg.Induced_neural_progenitors [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Neu.50.AllAg.Induced_neural_progenitors mm9 TFs and others Neural Induced neura...l progenitors SRX323564,SRX323573 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.50.AllAg.Induced_neural_progenitors.bed ...

  16. File list: Oth.Adp.10.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Adp.10.AllAg.Adipose_progenitor_cells mm9 TFs and others Adipocyte Adipose prog...enitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Adp.10.AllAg.Adipose_progenitor_cells.bed ...

  17. File list: Unc.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Adp.20.AllAg.Adipose_progenitor_cells mm9 Unclassified Adipocyte Adipose progen...itor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Adp.20.AllAg.Adipose_progenitor_cells.bed ...

  18. File list: DNS.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adp.50.AllAg.Adipose_progenitor_cells mm9 DNase-seq Adipocyte Adipose progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Adp.50.AllAg.Adipose_progenitor_cells.bed ...

  19. File list: DNS.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adp.20.AllAg.Adipose_progenitor_cells mm9 DNase-seq Adipocyte Adipose progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Adp.20.AllAg.Adipose_progenitor_cells.bed ...

  20. File list: Unc.Adp.10.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Adp.10.AllAg.Adipose_progenitor_cells mm9 Unclassified Adipocyte Adipose progen...itor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Adp.10.AllAg.Adipose_progenitor_cells.bed ...

  1. File list: Unc.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Adp.05.AllAg.Adipose_progenitor_cells mm9 Unclassified Adipocyte Adipose progen...itor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Adp.05.AllAg.Adipose_progenitor_cells.bed ...

  2. File list: Unc.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Adp.50.AllAg.Adipose_progenitor_cells mm9 Unclassified Adipocyte Adipose progen...itor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Adp.50.AllAg.Adipose_progenitor_cells.bed ...

  3. File list: Oth.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Adp.05.AllAg.Adipose_progenitor_cells mm9 TFs and others Adipocyte Adipose prog...enitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Adp.05.AllAg.Adipose_progenitor_cells.bed ...

  4. File list: His.Adp.10.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Adp.10.AllAg.Adipose_progenitor_cells mm9 Histone Adipocyte Adipose progenitor ...cells SRX127409,SRX127394,SRX127396,SRX127407,SRX127383,SRX127381 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Adp.10.AllAg.Adipose_progenitor_cells.bed ...

  5. File list: His.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Adp.20.AllAg.Adipose_progenitor_cells mm9 Histone Adipocyte Adipose progenitor ...cells SRX127394,SRX127409,SRX127396,SRX127407,SRX127381,SRX127383 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Adp.20.AllAg.Adipose_progenitor_cells.bed ...

  6. File list: Pol.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adp.20.AllAg.Adipose_progenitor_cells mm9 RNA polymerase Adipocyte Adipose prog...enitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Adp.20.AllAg.Adipose_progenitor_cells.bed ...

  7. File list: DNS.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adp.05.AllAg.Adipose_progenitor_cells mm9 DNase-seq Adipocyte Adipose progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Adp.05.AllAg.Adipose_progenitor_cells.bed ...

  8. File list: Oth.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Adp.20.AllAg.Adipose_progenitor_cells mm9 TFs and others Adipocyte Adipose prog...enitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Adp.20.AllAg.Adipose_progenitor_cells.bed ...

  9. File list: Pol.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adp.50.AllAg.Adipose_progenitor_cells mm9 RNA polymerase Adipocyte Adipose prog...enitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Adp.50.AllAg.Adipose_progenitor_cells.bed ...

  10. File list: His.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Adp.05.AllAg.Adipose_progenitor_cells mm9 Histone Adipocyte Adipose progenitor ...cells SRX127409,SRX127407,SRX127394,SRX127396,SRX127383,SRX127381 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Adp.05.AllAg.Adipose_progenitor_cells.bed ...

  11. File list: Pol.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adp.05.AllAg.Adipose_progenitor_cells mm9 RNA polymerase Adipocyte Adipose prog...enitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Adp.05.AllAg.Adipose_progenitor_cells.bed ...

  12. File list: DNS.Adp.10.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adp.10.AllAg.Adipose_progenitor_cells mm9 DNase-seq Adipocyte Adipose progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Adp.10.AllAg.Adipose_progenitor_cells.bed ...

  13. File list: Unc.Neu.50.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Neu.50.AllAg.Neural_progenitor_cells mm9 Unclassified Neural Neural progenitor ...cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.50.AllAg.Neural_progenitor_cells.bed ...

  14. File list: His.Neu.20.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.20.AllAg.Neural_progenitor_cells mm9 Histone Neural Neural progenitor cells... SRX315278,SRX667383,SRX668241,SRX315277,SRX315276 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.20.AllAg.Neural_progenitor_cells.bed ...

  15. File list: Pol.Neu.20.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.20.AllAg.Neural_progenitor_cells mm9 RNA polymerase Neural Neural progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.20.AllAg.Neural_progenitor_cells.bed ...

  16. File list: His.Neu.10.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Neu.10.AllAg.Neural_progenitor_cells mm9 Histone Neural Neural progenitor cells... SRX315278,SRX315277,SRX667383,SRX668241,SRX315276 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.10.AllAg.Neural_progenitor_cells.bed ...

  17. File list: ALL.Neu.05.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Neu.05.AllAg.Neural_progenitor_cells mm9 All antigens Neural Neural progenitor ...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.05.AllAg.Neural_progenitor_cells.bed ...

  18. File list: Pol.Neu.10.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.10.AllAg.Neural_progenitor_cells mm9 RNA polymerase Neural Neural progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.10.AllAg.Neural_progenitor_cells.bed ...

  19. File list: Pol.Neu.05.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Neu.05.AllAg.Neural_progenitor_cells mm9 RNA polymerase Neural Neural progenito...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.05.AllAg.Neural_progenitor_cells.bed ...

  20. File list: DNS.Neu.50.AllAg.Neural_progenitor_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Neu.50.AllAg.Neural_progenitor_cells mm9 DNase-seq Neural Neural progenitor cel...ls SRX238870,SRX238868 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.50.AllAg.Neural_progenitor_cells.bed ...