Oxygen Sensing Mesenchymal Progenitors Promote Neo-Vasculogenesis in a Humanized Mouse Model In Vivo
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{"title"=>"Oxygen Sensing Mesenchymal Progenitors Promote Neo-Vasculogenesis in a Humanized Mouse Model In Vivo", "type"=>"journal", "authors"=>[{"first_name"=>"Nicole A.", "last_name"=>"Hofmann", "scopus_author_id"=>"56694169300"}, {"first_name"=>"Anna", "last_name"=>"Ortner", "scopus_author_id"=>"54786784900"}, {"first_name"=>"Rodrigo O.", "last_name"=>"Jacamo", "scopus_author_id"=>"8633891300"}, {"first_name"=>"Andreas", "last_name"=>"Reinisch", "scopus_author_id"=>"17346703200"}, {"first_name"=>"Katharina", "last_name"=>"Schallmoser", "scopus_author_id"=>"6602574635"}, {"first_name"=>"Rokhsareh", "last_name"=>"Rohban", "scopus_author_id"=>"35107959400"}, {"first_name"=>"Nathalie", "last_name"=>"Etchart", "scopus_author_id"=>"57195036624"}, {"first_name"=>"Margareta", "last_name"=>"Fruehwirth", "scopus_author_id"=>"55355527500"}, {"first_name"=>"Christine", "last_name"=>"Beham-Schmid", "scopus_author_id"=>"6701322682"}, {"first_name"=>"Michael", "last_name"=>"Andreeff", "scopus_author_id"=>"35377715500"}, {"first_name"=>"Dirk", "last_name"=>"Strunk", "scopus_author_id"=>"6602991269"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84866107352", "sgr"=>"84866107352", "doi"=>"10.1371/journal.pone.0044468", "pui"=>"365625440", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"22970226"}, "id"=>"13d16166-d79d-3f72-b2eb-c0288a95fd47", "abstract"=>"Despite insights into the molecular pathways regulating hypoxia-induced gene expression, it is not known which cell types accomplish oxygen sensing during neo-vasculogenesis. We have developed a humanized mouse model of endothelial and mesenchymal progenitor co-transplantation to delineate the cellular compartments responsible for hypoxia response during vasculogenesis. Mesenchymal stem/progenitor cells (MSPCs) accumulated nuclear hypoxia-inducible transcription factor (HIF)-1α earlier and more sensitively than endothelial colony forming progenitor cells (ECFCs) in vitro and in vivo. Hypoxic ECFCs showed reduced function in vitro and underwent apoptosis within 24h in vivo when used without MSPCs. Surprisingly, only in MSPCs did pharmacologic or genetic inhibition of HIF-1α abrogate neo-vasculogenesis. HIF deletion in ECFCs caused no effect. ECFCs could be rescued from hypoxia-induced apoptosis by HIF-competent MSPCs resulting in the formation of patent perfused human vessels. Several angiogenic factors need to act in concert to partially substitute mesenchymal HIF-deficiency. Results demonstrate that ECFCs require HIF-competent vessel wall progenitors to initiate vasculogenesis in vivo and to bypass hypoxia-induced apoptosis. We describe a novel mechanistic role of MSPCs as oxygen sensors promoting vasculogenesis thus underscoring their importance for the development of advanced cellular therapies.", "link"=>"http://www.mendeley.com/research/oxygen-sensing-mesenchymal-progenitors-promote-neovasculogenesis-humanized-mouse-model-vivo", "reader_count"=>30, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>7, "Other"=>2, "Student > Bachelor"=>4, "Professor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>7, "Other"=>2, "Student > Bachelor"=>4, "Professor"=>5}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>15, "Medicine and Dentistry"=>4, "Chemistry"=>1, "Social Sciences"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>15}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>1, "Germany"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/580297"], "description"=>"<p>(<b>A</b>) Vessel formation was determined 2 weeks after ECFC+MSPC (2×10<sup>6</sup> cells/300µL, ratio of 80∶20) co-transplantation. Pre-treatment of one of the two co-transplanted cell populations with YC-1 (1 h, 37°C; ECFC<sup>+YC1</sup>+MSPC, n = 3; ECFC + MSPC<sup>+YC1</sup>, n = 5) compared to untreated transplants (ECFC+MSPC, n = 8) as indicated above each column. Hematoxylin/eosin (HE) staining visualizes morphology (first row; scale bar 200 µm) and the mouse red blood cells (mRBC) resulting from perfusion after connection to the recipients’ circulation (Ter119 anti- mouse glycophorin reactivity, red; 4′,6-Diamidin-2-phenylindol, DAPI, blue; second row; scale bar 200 µm). Human mesodermal origin was visualized with anti-human vimentin monoclonal antibody staining (h.Vimentin, brown; mouse and human nuclei counterstained with hematoxylin, blue; third row; scale bar 50 µm). Plugs contain different numbers of h.Vimentin-negative infiltrating mouse CD45<sup>+</sup> hematopoietic cells (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044468#pone.0044468.s006\" target=\"_blank\">Figure S6C</a>). Fourth row indicating presence or absence of human vessels stained with rabbit anti-human CD31 labeling ECFCs (h.CD31, green), mouse anti-human alpha smooth muscle actin labeling pericytes and mural smooth muscle cells (h.SMA, red) and nuclear counter-stain (DAPI, blue; scale bar 20 µm). (<b>B</b>) Microvessel density was quantified in 200x magnifications of HE stained Matrigel plug sections by ImageJ and counting red blood cell-filled vessel structures. A significantly decreased capacity to form perfused vessels was found in implants containing YC-1 pre-treated MSPCs compared to untreated co-transplants. (n = 3, 5 high power fields 200x; ***p<0.0001).</p>", "links"=>[], "tags"=>["progenitor", "co-transplantation", "depends", "hypoxia-induced", "factors", "mspcs"], "article_id"=>250779, "categories"=>["Biotechnology", "Cell Biology", "Developmental Biology", "Hematology"], "users"=>["Nicole A. Hofmann", "Anna Ortner", "Rodrigo O. Jacamo", "Andreas Reinisch", "Katharina Schallmoser", "Rokhsareh Rohban", "Nathalie Etchart", "Margareta Fruehwirth", "Christine Beham-Schmid", "Michael Andreeff", "Dirk Strunk"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044468.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Human_vessel_formation_after_progenitor_co_transplantation_depends_on_hypoxia_induced_factors_in_MSPCs_but_not_ECFCs_/250779", "title"=>"Human vessel formation after progenitor co-transplantation depends on hypoxia-induced factors in MSPCs but not ECFCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-07 00:12:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/580138"], "description"=>"<p>(<b>A</b>) Vascular-like structures documented 24 h after seeding 1.8×10<sup>5</sup> ECFCs per 10 cm<sup>2</sup> on top of a matrix gel in a standard angiogenesis assay showing impaired network formation by ECFCs at 1% more than at 5% O<sub>2</sub> (upper row) and resumed vessel-like structure formation after re-oxygenation back to 20% O<sub>2</sub> standard conditions (+reoxy, lower row; one representative picture series; n = 3). (<b>B</b>) Tube number (black bar) and length (grey bar) as determined using ImageJ software (<a href=\"http://rsbweb.nih.gov\" target=\"_blank\">http://rsbweb.nih.gov</a>) were significantly reduced with decreasing O<sub>2</sub> (mean ± SD; *p<0.05; n = 4). (<b>C</b>) Wounding an ECFC-derived monolayer in a scratch assay was used to monitor endothelial wound repair under hypoxia (1% O2) as compared to reduced (5% O<sub>2</sub>) and ambient air (20% O<sub>2</sub>) standard laboratory test conditions (representative examples are shown; see also <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044468#pone.0044468.s009\" target=\"_blank\">Video S1</a>). (<b>D</b>) A significantly decreased capacity to close an endothelial wound area over time was found at 1% O<sub>2</sub> compared to 20% O<sub>2</sub> (n = 5; *p<0.05, **p<0.001).</p>", "links"=>[], "tags"=>["quiescence", "progenitor", "cells", "hypoxia"], "article_id"=>250618, "categories"=>["Biotechnology", "Cell Biology", "Developmental Biology", "Hematology"], "users"=>["Nicole A. Hofmann", "Anna Ortner", "Rodrigo O. Jacamo", "Andreas Reinisch", "Katharina Schallmoser", "Rokhsareh Rohban", "Nathalie Etchart", "Margareta Fruehwirth", "Christine Beham-Schmid", "Michael Andreeff", "Dirk Strunk"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044468.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_quiescence_of_progenitor_cells_under_hypoxia_in_vitro_/250618", "title"=>"Functional quiescence of progenitor cells under hypoxia <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-07 00:10:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/579991"], "description"=>"<p>(<b>A</b>) Immune histochemical staining of Matrigel plugs 1 day (d) after implantation of either ECFCs only (left picture), ECFCs/MSPCs together (middle picture) or MSPCs only (right picture). Plugs were explanted and sections were stained with anti-HIF-1α (DAB, brown) and co-stained with hematoxylin (blue; scale bar 50 µm). Staining revealed that 100% of MSPCs display positive signals for HIF-1α, while ECFCs alone show no HIF-1α stabilization and in plugs of ECFCs together with MSPCs the number of positive cells corresponds to the 20% MSPCs. (<b>B</b>) To measure the hypoxia response at the single cell level <i>in vitro</i>, ECFCs and MSPCs were cultured for 4 h at 1%, 5% and 20% O<sub>2</sub>. Phase contrast microphotographs show an unchanged appearance. Hypoxyprobe (pimonidazole, green; 4′,6-Diamidin-2-phenylindol, DAPI nuclear stain in blue) revealed that MSPCs sense hypoxia at 5% O<sub>2</sub> and both ECFCs and MSPCs sense hypoxia at 1% O<sub>2</sub>. Accordingly, nuclear HIF-1α protein accumulation was detected in MSPCs at 5% and in both progenitor cell types at 1% O<sub>2</sub> (scale bar 100 µm for phase contrast and pimonidazole and 20 µm for HIF-1α pictures). (<b>C</b>) Equal amounts of protein from cell lysates corresponding to the analysis in (B) were tested in western blots showing higher amounts of HIF-1α in MSPCs. MSPCs stabilize HIF-1α at 5% and display a minute baseline signal at ambient air levels of 20% O<sub>2</sub> (n = 3; representative blot regions are shown; see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044468#pone.0044468.s001\" target=\"_blank\">Figure S1E</a> for complete blot scans).</p>", "links"=>[], "tags"=>["cells", "hypoxia", "endothelial"], "article_id"=>250472, "categories"=>["Biotechnology", "Cell Biology", "Developmental Biology", "Hematology"], "users"=>["Nicole A. Hofmann", "Anna Ortner", "Rodrigo O. Jacamo", "Andreas Reinisch", "Katharina Schallmoser", "Rokhsareh Rohban", "Nathalie Etchart", "Margareta Fruehwirth", "Christine Beham-Schmid", "Michael Andreeff", "Dirk Strunk"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044468.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mural_cells_are_more_sensitive_to_hypoxia_than_endothelial_cells_/250472", "title"=>"Mural cells are more sensitive to hypoxia than endothelial cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-07 00:07:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/580447"], "description"=>"<p>(<b>A</b>) Total cell lysates of untreated control (<b>−</b>) ECFCs and MSPCs or after infection with either pGIPZ-HIF1α-shRNA (shHIF-1α) or non-specific pGIPZ-scramble-shRNA (NS) were separated by SDS-PAGE after 6 hours of incubation at 1% O<sub>2</sub>. Blots were stained with HIF-1α, HIF-2α, HIF-1β or β-actin (β-Act). Full blots are shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044468#pone.0044468.s002\" target=\"_blank\">Figure S2</a>. (<b>B</b>) To delineate the impact of genetic ablation of HIF-1α in either ECFCs or MSPCs before co-transplantation, vessel formation was determined one week after co-transplantation of HIF-1α-silenced (ECFC<sup>shHIF-1α</sup>, n = 3; MSPC<sup>shHIF-1α</sup>, n = 7) or mock-transfected non-silenced cells (ECFC<sup>NS</sup>, n = 3; MSPC<sup>NS</sup>, n = 7) with genetically un-manipulated corresponding (+ECFC and +MSPC) partner cells as indicated above the columns. Analysis was performed as specified in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044468#pone-0044468-g003\" target=\"_blank\">Figure 3A</a> and is identified at the left side of the picture. Scale bars indicate magnification (first and second row, 200 µm; third row, 50 µm; fourth row, 20 µm). (<b>C</b>) Microvessel density was quantified in 200x magnifications of HE stained Matrigel plug sections by ImageJ counting red blood cell filled vessel structures. A significantly decreased capacity to form perfused vessels was found in implants containing shHIF-1α transfected MSPCs compared to untreated co-transplants. (n = 3, 5 high power fields 200x, mean ± SEM; ***p<0.0001).</p>", "links"=>[], "tags"=>["knock-down", "mspcs", "ecfcs", "inhibits"], "article_id"=>250933, "categories"=>["Biotechnology", "Cell Biology", "Developmental Biology", "Hematology"], "users"=>["Nicole A. Hofmann", "Anna Ortner", "Rodrigo O. Jacamo", "Andreas Reinisch", "Katharina Schallmoser", "Rokhsareh Rohban", "Nathalie Etchart", "Margareta Fruehwirth", "Christine Beham-Schmid", "Michael Andreeff", "Dirk Strunk"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044468.g004", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Specific_knock_down_of_HIF_1_in_MSPCs_but_not_in_ECFCs_inhibits_vessel_formation_in_vivo_/250933", "title"=>"Specific knock-down of HIF-1α in MSPCs but not in ECFCs inhibits vessel formation <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-07 00:15:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/580839"], "description"=>"<p>(<b>A</b>) The experimental strategy to delineate the hypoxia response used pre-treatment of either ECFCs or MSPCs before transplantation with YC-1 (inhibiting both HIF-1α as well as HIF-2α) or specific knockdown of HIF-1α RNA (by sh-RNA;). The surprising outcome of vessel formation despite the inhibition of ECFC hypoxia response and collapse of neo-vasculogenesis after MSPC inhibition is graphically illustrated. (<b>B</b>) Based on our current insight a model is proposed describing three temporarily distinct phases of adult vasculogenesis.</p>", "links"=>[], "tags"=>["sensing", "induction"], "article_id"=>251323, "categories"=>["Biotechnology", "Cell Biology", "Developmental Biology", "Hematology"], "users"=>["Nicole A. Hofmann", "Anna Ortner", "Rodrigo O. Jacamo", "Andreas Reinisch", "Katharina Schallmoser", "Rokhsareh Rohban", "Nathalie Etchart", "Margareta Fruehwirth", "Christine Beham-Schmid", "Michael Andreeff", "Dirk Strunk"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044468.g007", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MSPCs_are_responsible_for_oxygen_sensing_and_induction_of_neo_vasculogenesis_/251323", "title"=>"MSPCs are responsible for oxygen sensing and induction of neo-vasculogenesis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-07 00:22:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/580705"], "description"=>"<p>ECFCs alone or in combination with MSPCs (either un-manipulated or after shHIF-1α knockdown) were (co)-transplanted in either Matrigel or pooled human platelet lysate (pHPL) gel with or without additional growth factors (GF) as specified. The GF-Mix comprised VEGF, EGF, IGF, FGF-2, hydrocortisone and ascorbic acid. Mean ± SD results of the number of perfused vessels counted in five high power fields (200x, at least two independent plugs and two independent animals). Microphotographs correspond to the treatment group (scale bar 50 µm; ***p<0.0001, *p<0.05).</p>", "links"=>[], "tags"=>["factors", "substitute", "mspc", "deficiency"], "article_id"=>251193, "categories"=>["Biotechnology", "Cell Biology", "Developmental Biology", "Hematology"], "users"=>["Nicole A. Hofmann", "Anna Ortner", "Rodrigo O. Jacamo", "Andreas Reinisch", "Katharina Schallmoser", "Rokhsareh Rohban", "Nathalie Etchart", "Margareta Fruehwirth", "Christine Beham-Schmid", "Michael Andreeff", "Dirk Strunk"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044468.g006", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Angiogenic_factors_can_partially_substitute_MSPC_HIF_1_deficiency_in_vivo_/251193", "title"=>"Angiogenic factors can partially substitute MSPC HIF-1α deficiency <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-07 00:19:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/580605"], "description"=>"<p>(<b>A</b>) Apoptosis assay using TdT-mediated dUTP nick end labeling (TUNEL) of ECFC-only or MSPC-only transplants and treated or untreated ECFC+MSPC co-transplants, as indicated above each photograph. All plugs were explanted 24 h after implantation <i>in vivo</i>. DNA strand breaks of apoptotic cells were detected by a TUNEL assay kit (Promega) and nuclei were counterstained with propidium iodide (PI, red). Green fluorescence is due to FITC-labeled nucleotide binding to DNA strand breaks of apoptotic cells. Representative pictures from one experiment are shown (scale bar 100 µm, from at least three different donors performed per transplantation type as specified in the legends to <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044468#pone-0044468-g003\" target=\"_blank\">Figures 3</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044468#pone-0044468-g004\" target=\"_blank\">4</a>). (<b>B</b>) Apoptotic cells depicted as percentage of total cells ± SD with groups corresponding to the representative pictures in (A); five high power fields 200x; ***p<0.0001, **p<0.01).</p>", "links"=>[], "tags"=>["mspcs", "premature", "ecfc", "apoptosis"], "article_id"=>251093, "categories"=>["Biotechnology", "Cell Biology", "Developmental Biology", "Hematology"], "users"=>["Nicole A. Hofmann", "Anna Ortner", "Rodrigo O. Jacamo", "Andreas Reinisch", "Katharina Schallmoser", "Rokhsareh Rohban", "Nathalie Etchart", "Margareta Fruehwirth", "Christine Beham-Schmid", "Michael Andreeff", "Dirk Strunk"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044468.g005", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HIF_competent_MSPCs_are_required_to_avoid_premature_ECFC_apoptosis_in_vivo_/251093", "title"=>"HIF-competent MSPCs are required to avoid premature ECFC apoptosis <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-07 00:18:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/306098", "https://ndownloader.figshare.com/files/306141", "https://ndownloader.figshare.com/files/306192", "https://ndownloader.figshare.com/files/306251", "https://ndownloader.figshare.com/files/306300", "https://ndownloader.figshare.com/files/306393", "https://ndownloader.figshare.com/files/306459", "https://ndownloader.figshare.com/files/306524", "https://ndownloader.figshare.com/files/306606"], "description"=>"<div><p>Despite insights into the molecular pathways regulating hypoxia-induced gene expression, it is not known which cell types accomplish oxygen sensing during neo-vasculogenesis. We have developed a humanized mouse model of endothelial and mesenchymal progenitor co-transplantation to delineate the cellular compartments responsible for hypoxia response during vasculogenesis. Mesenchymal stem/progenitor cells (MSPCs) accumulated nuclear hypoxia-inducible transcription factor (HIF)-1α earlier and more sensitively than endothelial colony forming progenitor cells (ECFCs) <em>in vitro</em> and <em>in vivo</em>. Hypoxic ECFCs showed reduced function <em>in vitro</em> and underwent apoptosis within 24h <em>in vivo</em> when used without MSPCs. Surprisingly, only in MSPCs did pharmacologic or genetic inhibition of HIF-1α abrogate neo-vasculogenesis. HIF deletion in ECFCs caused no effect. ECFCs could be rescued from hypoxia-induced apoptosis by HIF-competent MSPCs resulting in the formation of patent perfused human vessels. Several angiogenic factors need to act in concert to partially substitute mesenchymal HIF-deficiency. Results demonstrate that ECFCs require HIF-competent vessel wall progenitors to initiate vasculogenesis <em>in vivo</em> and to bypass hypoxia-induced apoptosis. We describe a novel mechanistic role of MSPCs as oxygen sensors promoting vasculogenesis thus underscoring their importance for the development of advanced cellular therapies.</p> </div>", "links"=>[], "tags"=>["sensing", "mesenchymal", "progenitors", "neo-vasculogenesis", "humanized"], "article_id"=>120388, "categories"=>["Biotechnology", "Cell Biology", "Developmental Biology", "Hematology"], "users"=>["Nicole A. Hofmann", "Anna Ortner", "Rodrigo O. Jacamo", "Andreas Reinisch", "Katharina Schallmoser", "Rokhsareh Rohban", "Nathalie Etchart", "Margareta Fruehwirth", "Christine Beham-Schmid", "Michael Andreeff", "Dirk Strunk"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0044468.s001", "https://dx.doi.org/10.1371/journal.pone.0044468.s002", "https://dx.doi.org/10.1371/journal.pone.0044468.s003", "https://dx.doi.org/10.1371/journal.pone.0044468.s004", "https://dx.doi.org/10.1371/journal.pone.0044468.s005", "https://dx.doi.org/10.1371/journal.pone.0044468.s006", "https://dx.doi.org/10.1371/journal.pone.0044468.s007", "https://dx.doi.org/10.1371/journal.pone.0044468.s008", "https://dx.doi.org/10.1371/journal.pone.0044468.s009"], "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Oxygen_Sensing_Mesenchymal_Progenitors_Promote_Neo_Vasculogenesis_in_a_Humanized_Mouse_Model_In_Vivo_/120388", "title"=>"Oxygen Sensing Mesenchymal Progenitors Promote Neo-Vasculogenesis in a Humanized Mouse Model <em>In Vivo</em>", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-09-07 00:06:28"}

PMC Usage Stats | Further Information

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