Mobilization of Endogenous Bone Marrow Derived Endothelial Progenitor Cells and Therapeutic Potential of Parathyroid Hormone after Ischemic Stroke in Mice
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{"title"=>"Mobilization of Endogenous Bone Marrow Derived Endothelial Progenitor Cells and Therapeutic Potential of Parathyroid Hormone after Ischemic Stroke in Mice", "type"=>"journal", "authors"=>[{"first_name"=>"Li-Li", "last_name"=>"Wang"}, {"first_name"=>"Dongdong", "last_name"=>"Chen"}, {"first_name"=>"Jinhwan", "last_name"=>"Lee"}, {"first_name"=>"Xiaohuan", "last_name"=>"Gu"}, {"first_name"=>"Ghina", "last_name"=>"Alaaeddine"}, {"first_name"=>"Jimei", "last_name"=>"Li"}, {"first_name"=>"Ling", "last_name"=>"Wei"}, {"first_name"=>"Shan Ping", "last_name"=>"Yu"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0087284", "pmid"=>"24503654"}, "id"=>"af126c1f-f942-38cd-855d-9c6092ba5130", "abstract"=>"Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH) therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p.) was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1) positive endothelial progenitor cells (EPCs) in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ) and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke.", "link"=>"http://www.mendeley.com/research/mobilization-endogenous-bone-marrow-derived-endothelial-progenitor-cells-therapeutic-potential-parat", "reader_count"=>21, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>3, "Student > Master"=>1, "Student > Bachelor"=>1, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>3, "Student > Master"=>1, "Student > Bachelor"=>1, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>12, "Agricultural and Biological Sciences"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>12}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>1, "India"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1375212"], "description"=>"<p>Fourteen days after stroke, endothelial cells and cell proliferation at the peri-infarct region was inspected using immunohistochemical methods. <b>A</b> and <b>B</b>. Representative Glut-1 (green) staining of vascular endothelial cells in the brain section from stroke/saline and stroke/PTH mice. <b>C</b>. The area of Glut-1 fluorescent reactivity in stroke/saline and stroke/PTH groups. <b>D</b> to <b>I</b>. Fluorescent labeling of Glut-1+ (green) and BrdU+ (red) cells. F and I are 3-D images showing co-localized labeling of Glut-1 and BrdU, indicative of angiogenesis. <b>J</b>. Quantified data of fluorescent reactivity of Glut-1/BrdU double positive cells; PTH treatment significantly promoted angiogenesis. N = 6; ** <i>P</i><0.01 vs. stroke control.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Endocrine system", "Endocrine physiology", "hormones", "Model organisms", "Animal models", "mouse", "Molecular cell biology", "Cellular types", "stem cells", "neuroscience", "Cellular neuroscience", "Neurobiology of disease and regeneration", "neurology", "Cerebrovascular diseases", "Ischemic stroke", "enhanced", "angiogenesis", "peri-infarct", "14", "days"], "article_id"=>925376, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Li-li Wang", "Dongdong Chen", "Jinhwan Lee", "Xiaohuan Gu", "Ghina Alaaeddine", "Jimei Li", "Ling Wei", "Shan Ping Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087284.g003", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PTH_enhanced_angiogenesis_at_the_peri_infarct_region_14_days_after_stroke_/925376", "title"=>"PTH enhanced angiogenesis at the peri-infarct region 14 days after stroke.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-04 03:24:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1375210"], "description"=>"<p>Six days after stroke with PTH or saline treatment, blood samples were collected. FITC-conjugated CD34 and PE-conjugated VEGFR2/Flk1/KDR labeled cell populations were measured by BD FACSCalibur flow cytometer. <b>A</b>–<b>C</b>. Representative results of Fluorescence Activated Cell Sorting (FACS) are shown in A (sham control), B (stroke plus saline), and C (stroke plus PTH). <b>D</b>. The bar graph shows quantified data with a significant increase in CD34+/Flk1+ cells in stroke plus PTH group. N = 5 animals in each of the three groups; * <i>P</i><0.05 vs. sham and stroke controls.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Endocrine system", "Endocrine physiology", "hormones", "Model organisms", "Animal models", "mouse", "Molecular cell biology", "Cellular types", "stem cells", "neuroscience", "Cellular neuroscience", "Neurobiology of disease and regeneration", "neurology", "Cerebrovascular diseases", "Ischemic stroke", "endothelial", "progenitor", "cells", "peripheral"], "article_id"=>925374, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Li-li Wang", "Dongdong Chen", "Jinhwan Lee", "Xiaohuan Gu", "Ghina Alaaeddine", "Jimei Li", "Ling Wei", "Shan Ping Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087284.g001", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PTH_increased_the_endothelial_progenitor_cells_in_the_peripheral_blood_/925374", "title"=>"PTH increased the endothelial progenitor cells in the peripheral blood.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-04 03:24:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1375215"], "description"=>"<p>Neurogenesis in the peri-infarct region was examined by the colocalization of the neuronal marker NeuN (red) and the proliferation marker BrdU (green) 21 days after stroke. <b>A</b> to <b>C</b>. Immunostaining images of NeuN+ cells (A), BrdU+ cells (B) and the merged image of NeuN+ and BrdU+ cells (C). <b>D</b>. Enlarged images of colocalization of NeuN/BrdU from the frame shown in C. <b>E</b>. Cell counts were performed in six randomly chosen fields per section in the peri-infarct region. The total number of cells in six sections was summarized for each mouse. Cell counts show increased numbers of Neu+/BrdU+ cells in the PTH treatment group compared with the stroke/saline group. N = 6 animals each group, *** <i>P</i><0.001 vs. stroke controls.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Endocrine system", "Endocrine physiology", "hormones", "Model organisms", "Animal models", "mouse", "Molecular cell biology", "Cellular types", "stem cells", "neuroscience", "Cellular neuroscience", "Neurobiology of disease and regeneration", "neurology", "Cerebrovascular diseases", "Ischemic stroke", "enhanced", "neurogenesis", "peri-infarct", "21", "days"], "article_id"=>925379, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Li-li Wang", "Dongdong Chen", "Jinhwan Lee", "Xiaohuan Gu", "Ghina Alaaeddine", "Jimei Li", "Ling Wei", "Shan Ping Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087284.g006", "stats"=>{"downloads"=>2, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PTH_enhanced_neurogenesis_at_the_peri_infarct_region_21_days_after_stoke_/925379", "title"=>"PTH enhanced neurogenesis at the peri-infarct region 21 days after stoke.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-04 03:24:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1375214"], "description"=>"<p>The neuroblast migration and regenerative activity along the ipsilateral SVZ to ischemic cortex migration route was examined by immunostaining of migrating neural progenitor marker DCX (green) and the proliferating marker BrdU (red) 6 days after the onset of ischemia. <b>A</b>. In the post ischemic brain there was significant neuroblast migration from the SVZ to the ischemic barrel cortex (*). Noticeably more DCX and BudU positive cells can be seen in the migration path of PTH treated animals (B) than in the stroke/saline brain (A). <b>C</b>. The total number of DCX+/BrdU+ cells in six sections per animal was counted under a fluorescent microscope. Double-labeling of DCX/BrdU in white matter of ischemic stroke-saline (C) and PTH treated mice (D) 6 days after ischemia. PTH treatment promoted more DCX/BrdU-positive cells moving toward the ischemic cortex (F). The number of DCX+/BrdU+ cells in stroke control and stroke/PTH groups. PTH treatment markedly augmented the proliferating activity among DCX+ cells. <b>D</b>. PTH treatment increased the average migration distance from the SVZ toward the ischemic barrel cortex. N = 6 in stroke/saline group and 7 in stroke/PTH group; * <i>P</i><0.05 vs. stroke controls, ** <i>P</i><0.01 vs. stroke controls.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Endocrine system", "Endocrine physiology", "hormones", "Model organisms", "Animal models", "mouse", "Molecular cell biology", "Cellular types", "stem cells", "neuroscience", "Cellular neuroscience", "Neurobiology of disease and regeneration", "neurology", "Cerebrovascular diseases", "Ischemic stroke", "enhanced", "neuroblast", "svz", "ischemic"], "article_id"=>925378, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Li-li Wang", "Dongdong Chen", "Jinhwan Lee", "Xiaohuan Gu", "Ghina Alaaeddine", "Jimei Li", "Ling Wei", "Shan Ping Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087284.g005", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PTH_treatment_enhanced_neuroblast_migration_from_the_SVZ_to_the_ischemic_cortex_/925378", "title"=>"PTH treatment enhanced neuroblast migration from the SVZ to the ischemic cortex.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-04 03:24:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1375217"], "description"=>"<div><p>Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH) therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p.) was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1) positive endothelial progenitor cells (EPCs) in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ) and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke.</p></div>", "links"=>[], "tags"=>["Anatomy and physiology", "Endocrine system", "Endocrine physiology", "hormones", "Model organisms", "Animal models", "mouse", "Molecular cell biology", "Cellular types", "stem cells", "neuroscience", "Cellular neuroscience", "Neurobiology of disease and regeneration", "neurology", "Cerebrovascular diseases", "Ischemic stroke", "endogenous", "marrow", "derived", "endothelial", "progenitor", "cells", "therapeutic", "parathyroid", "ischemic"], "article_id"=>925381, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Li-li Wang", "Dongdong Chen", "Jinhwan Lee", "Xiaohuan Gu", "Ghina Alaaeddine", "Jimei Li", "Ling Wei", "Shan Ping Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087284", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mobilization_of_Endogenous_Bone_Marrow_Derived_Endothelial_Progenitor_Cells_and_Therapeutic_Potential_of_Parathyroid_Hormone_after_Ischemic_Stroke_in_Mice_/925381", "title"=>"Mobilization of Endogenous Bone Marrow Derived Endothelial Progenitor Cells and Therapeutic Potential of Parathyroid Hormone after Ischemic Stroke in Mice", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-04 03:24:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1375216"], "description"=>"<p>The adhesive-removal test was performed to evaluate sensorimotor deficits of the mice before, and 7 to 21 days after focal cerebral ischemia. <b>A</b>. All mice showed impaired function in this test (increased time to detect) after stroke. Mice that received PTH, however, exhibited significantly improved sensorimotor activity (faster detection of the sticky dot) at all time points tested. <b>B</b>. The time to removal of the sticky dot from the affected left paw was significantly increased in all stroke animals at 7 days after stroke. PTH treatment, however, improved this sensorimotor activity so that the time to removal was significantly shorter 14 days after stroke. N = 11–20 animals, * <i>P</i><0.05, ** <i>P</i><0.01 vs. stroke controls at the same time point.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Endocrine system", "Endocrine physiology", "hormones", "Model organisms", "Animal models", "mouse", "Molecular cell biology", "Cellular types", "stem cells", "neuroscience", "Cellular neuroscience", "Neurobiology of disease and regeneration", "neurology", "Cerebrovascular diseases", "Ischemic stroke", "promoted"], "article_id"=>925380, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Li-li Wang", "Dongdong Chen", "Jinhwan Lee", "Xiaohuan Gu", "Ghina Alaaeddine", "Jimei Li", "Ling Wei", "Shan Ping Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087284.g007", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PTH_treatment_promoted_functional_recovery_after_stroke_/925380", "title"=>"PTH treatment promoted functional recovery after stroke.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-04 03:24:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1375213"], "description"=>"<p>Local cerebral blood flow was measured using the PeriScans laser image scanner 14 days after stroke. <b>A</b>. Laser scanning images of LCBF in stroke/saline mice and stroke/PTH treatment mice before, during and 14 days after MCA occlusion. B. Sketch of the mouse skull showing the imaging area (square frame with arrow) for LCBF. The total scan area was 5.76 mm<sup>2</sup>. <b>C</b>. Quantification of LCBF measurements using the laser Doppler scanner. In this focal ischemia model of barrel cortex stroke, LCBF could largely recover 14 days after stroke. A greater recovery was seen with PTH treatment. N = 8 animals in each group; * <i>P</i><0.05 vs. stroke control.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Endocrine system", "Endocrine physiology", "hormones", "Model organisms", "Animal models", "mouse", "Molecular cell biology", "Cellular types", "stem cells", "neuroscience", "Cellular neuroscience", "Neurobiology of disease and regeneration", "neurology", "Cerebrovascular diseases", "Ischemic stroke", "cerebral", "ischemic"], "article_id"=>925377, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Li-li Wang", "Dongdong Chen", "Jinhwan Lee", "Xiaohuan Gu", "Ghina Alaaeddine", "Jimei Li", "Ling Wei", "Shan Ping Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087284.g004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Recovery_of_local_cerebral_blood_flow_in_the_ischemic_cortex_/925377", "title"=>"Recovery of local cerebral blood flow in the ischemic cortex.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-04 03:24:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1375211"], "description"=>"<p>The expression of key pro-regenerative factors in the peri-infarct region was detected using Western blot analysis. <b>A</b>. Electrophoresis gels show the protein levels of VEGF, BDNF, EPOR, SDF-1, and Tie-1 in the ischemic peri-infarct region in different animals 6 days after stroke. <b>B</b> to <b>F</b>. Densitometry analysis of the expression of BDNF (B), VEGF (C), EPOR (D), SDF-1 (E), and Tie-1 (F). Gray intensity was normalized against β-actin and quantified. PTH treatment significantly enhanced the expression of all these factors shown in A, compared with the stroke-saline group. N = 3 animals for each test; * <i>P</i><0.05.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Endocrine system", "Endocrine physiology", "hormones", "Model organisms", "Animal models", "mouse", "Molecular cell biology", "Cellular types", "stem cells", "neuroscience", "Cellular neuroscience", "Neurobiology of disease and regeneration", "neurology", "Cerebrovascular diseases", "Ischemic stroke", "pth", "angiogenic", "neurotrophic"], "article_id"=>925375, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Li-li Wang", "Dongdong Chen", "Jinhwan Lee", "Xiaohuan Gu", "Ghina Alaaeddine", "Jimei Li", "Ling Wei", "Shan Ping Yu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087284.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_PTH_on_the_expression_of_angiogenic_and_neurotrophic_factors_/925375", "title"=>"Effects of PTH on the expression of angiogenic and neurotrophic factors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-02-04 03:24:56"}

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