Discrepant Results of Experimental Human Mesenchymal Stromal Cell Therapy after Myocardial Infarction: Are Animal Models Robust Enough?
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{"title"=>"Discrepant Results of Experimental Human Mesenchymal Stromal Cell Therapy after Myocardial Infarction: Are Animal Models Robust Enough?", "type"=>"journal", "authors"=>[{"first_name"=>"Melina C", "last_name"=>"den Haan"}, {"first_name"=>"Vanessa-Leigh", "last_name"=>"van Zuylen"}, {"first_name"=>"Niek J", "last_name"=>"Pluijmert"}, {"first_name"=>"Cindy I", "last_name"=>"Schutte"}, {"first_name"=>"Willem E", "last_name"=>"Fibbe"}, {"first_name"=>"Martin J", "last_name"=>"Schalij"}, {"first_name"=>"Helene", "last_name"=>"Roelofs"}, {"first_name"=>"Douwe E", "last_name"=>"Atsma"}], "year"=>2016, "source"=>"PloS one", "identifiers"=>{"pmid"=>"27050443", "issn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0152938"}, "id"=>"3848c3a3-a110-394d-89f2-e20548c8e3eb", "abstract"=>"BACKGROUND: Human mesenchymal stromal cells (MSCs) have been reported to preserve cardiac function in myocardial infarction (MI) models. Previously, we found a beneficial effect of intramyocardial injection of unstimulated human MSCs (uMSCs) on cardiac function after permanent coronary artery ligation. In the present study we aimed to extend this research by investigating the effect of intramyocardial injection of human MSCs pre-stimulated with the pro-inflammatory cytokine interferon-gamma (iMSCs), since pro-inflammatory priming has shown additional salutary effects in multiple experimental disease models. METHODS: MI was induced in NOD/Scid mice by permanent ligation of the left anterior descending coronary artery. Animals received intramyocardial injection of uMSCs, iMSCs or PBS. Sham-operated animals were used to determine baseline characteristics. Cardiac performance was assessed after 2 and 14 days using 7-Tesla magnetic resonance imaging and pressure-volume loop measurements. Histology and q-PCR were used to confirm MSC engraftment in the heart. RESULTS: Both uMSC and iMSC therapy had no significant beneficial effect on cardiac function or remodelling in contrast to our previous studies. CONCLUSIONS: Animal models for cardiac MSC therapy appear less robust than initially envisioned.", "link"=>"http://www.mendeley.com/research/discrepant-results-experimental-human-mesenchymal-stromal-cell-therapy-after-myocardial-infarction-a-2", "reader_count"=>9, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>3, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>3, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>3, "Agricultural and Biological Sciences"=>3, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/4925146"], "description"=>"<div><p>Background</p><p>Human mesenchymal stromal cells (MSCs) have been reported to preserve cardiac function in myocardial infarction (MI) models. Previously, we found a beneficial effect of intramyocardial injection of unstimulated human MSCs (uMSCs) on cardiac function after permanent coronary artery ligation. In the present study we aimed to extend this research by investigating the effect of intramyocardial injection of human MSCs pre-stimulated with the pro-inflammatory cytokine interferon-gamma (iMSCs), since pro-inflammatory priming has shown additional salutary effects in multiple experimental disease models.</p><p>Methods</p><p>MI was induced in NOD/<i>Scid</i> mice by permanent ligation of the left anterior descending coronary artery. Animals received intramyocardial injection of uMSCs, iMSCs or PBS. Sham-operated animals were used to determine baseline characteristics. Cardiac performance was assessed after 2 and 14 days using 7-Tesla magnetic resonance imaging and pressure-volume loop measurements. Histology and q-PCR were used to confirm MSC engraftment in the heart.</p><p>Results</p><p>Both uMSC and iMSC therapy had no significant beneficial effect on cardiac function or remodelling in contrast to our previous studies.</p><p>Conclusions</p><p>Animal models for cardiac MSC therapy appear less robust than initially envisioned.</p></div>", "links"=>[], "tags"=>["Animal Models Robust", "intramyocardial injection", "Conclusions Animal models", "therapy", "artery", "PBS", "NOD", "MI", "Background Human mesenchymal stromal cells", "function", "ligation", "iMSC", "MSC", "Experimental Human Mesenchymal Stromal Cell Therapy", "uMSC"], "article_id"=>3162403, "categories"=>["Biophysics", "Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Biotechnology", "Immunology", "Developmental Biology", "Cancer", "Hematology", "Infectious Diseases"], "users"=>["Melina C. den Haan", "Vanessa-Leigh van Zuylen", "Niek J. Pluijmert", "Cindy I. Schutte", "Willem E. Fibbe", "Martin J. Schalij", "Helene Roelofs", "Douwe E. Atsma"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0152938", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Discrepant_Results_of_Experimental_Human_Mesenchymal_Stromal_Cell_Therapy_after_Myocardial_Infarction_Are_Animal_Models_Robust_Enough_/3162403", "title"=>"Discrepant Results of Experimental Human Mesenchymal Stromal Cell Therapy after Myocardial Infarction: Are Animal Models Robust Enough?", "pos_in_sequence"=>1, "defined_type"=>6, "published_date"=>"2016-04-06 04:58:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/4925428"], "description"=>"<p>A: Weight loss. B: Amount of pulmonary fluid. Data are expressed as mean ± SD. There were no significant differences between the uMSC, iMSC, PBS and Sham group.</p>", "links"=>[], "tags"=>["Animal Models Robust", "intramyocardial injection", "Conclusions Animal models", "therapy", "artery", "PBS", "NOD", "MI", "Background Human mesenchymal stromal cells", "function", "ligation", "iMSC", "MSC", "Experimental Human Mesenchymal Stromal Cell Therapy", "uMSC"], "article_id"=>3162613, "categories"=>["Biophysics", "Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Biotechnology", "Immunology", "Developmental Biology", "Cancer", "Hematology", "Infectious Diseases"], "users"=>["Melina C. den Haan", "Vanessa-Leigh van Zuylen", "Niek J. Pluijmert", "Cindy I. Schutte", "Willem E. Fibbe", "Martin J. Schalij", "Helene Roelofs", "Douwe E. Atsma"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0152938.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Physical_parameters_15_days_after_myocardial_infarction_in_uMSC_and_iMSC_treated_animals_uMSC_and_iMSC_resp_PBS_treated_animals_PBS_and_Sham_operated_animals_Sham_/3162613", "title"=>"Physical parameters 15 days after myocardial infarction in uMSC and iMSC treated animals (uMSC and iMSC, resp.), PBS treated animals (PBS) and Sham-operated animals (Sham).", "pos_in_sequence"=>6, "defined_type"=>1, "published_date"=>"2016-04-06 04:58:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/4925341"], "description"=>"<p>A: Left ventricular ejection fraction. B: End-diastolic volume. C: End-systolic volume. Data are expressed as mean ± SD. # = p<0.05 versus Sham. D: Pressure Volume loops of all treatment groups at day 15 after MI. The oblique lines represent the end-systolic (Ees) and end-diastolic (Eed) pressure–volume relations.</p>", "links"=>[], "tags"=>["Animal Models Robust", "intramyocardial injection", "Conclusions Animal models", "therapy", "artery", "PBS", "NOD", "MI", "Background Human mesenchymal stromal cells", "function", "ligation", "iMSC", "MSC", "Experimental Human Mesenchymal Stromal Cell Therapy", "uMSC"], "article_id"=>3162550, "categories"=>["Biophysics", "Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Biotechnology", "Immunology", "Developmental Biology", "Cancer", "Hematology", "Infectious Diseases"], "users"=>["Melina C. den Haan", "Vanessa-Leigh van Zuylen", "Niek J. Pluijmert", "Cindy I. Schutte", "Willem E. Fibbe", "Martin J. Schalij", "Helene Roelofs", "Douwe E. Atsma"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0152938.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Cardiac_function_as_assessed_by_7_T_MRI_at_2_and_14_days_after_myocardial_infarction_in_uMSC_and_iMSC_treated_animals_uMSC_and_iMSC_resp_PBS_treated_animals_PBS_and_Sham_operated_animals_Sham_panel_A_C_/3162550", "title"=>"Cardiac function as assessed by 7 T MRI at 2 and 14 days after myocardial infarction in uMSC and iMSC treated animals (uMSC and iMSC, resp.), PBS treated animals (PBS) and Sham-operated animals (Sham) (panel A-C).", "pos_in_sequence"=>4, "defined_type"=>1, "published_date"=>"2016-04-06 04:58:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/4925191"], "description"=>"<p>A: <i>In vitro</i> characterization of MSCs consisting of the specific surface marker antigen panel measured by flow cytometry. B: The differentiation capacity of MSCs towards osteoblasts shown by alkaline phosphatase activity and towards adipocytes shown by lipid droplets staining via Oil Red O. C: The inhibitory capacity of proliferation of activated peripheral blood mononuclear cells measured by 3H-thymidine uptake in counts per minute (CCPM). D: Bright light and fluorescence microscopy and flow cytometric analysis of eGFP labeling of lentivirally transduced MSCs.</p>", "links"=>[], "tags"=>["Animal Models Robust", "intramyocardial injection", "Conclusions Animal models", "therapy", "artery", "PBS", "NOD", "MI", "Background Human mesenchymal stromal cells", "function", "ligation", "iMSC", "MSC", "Experimental Human Mesenchymal Stromal Cell Therapy", "uMSC"], "article_id"=>3162439, "categories"=>["Biophysics", "Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Biotechnology", "Immunology", "Developmental Biology", "Cancer", "Hematology", "Infectious Diseases"], "users"=>["Melina C. den Haan", "Vanessa-Leigh van Zuylen", "Niek J. Pluijmert", "Cindy I. Schutte", "Willem E. Fibbe", "Martin J. Schalij", "Helene Roelofs", "Douwe E. Atsma"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0152938.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Characterization_of_primary_cultured_MSCs_/3162439", "title"=>"Characterization of primary cultured MSCs.", "pos_in_sequence"=>2, "defined_type"=>1, "published_date"=>"2016-04-06 04:58:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/4925467"], "description"=>"<p>Data are expressed as mean ± SD. There were no significant differences between the uMSC, iMSC, PBS and Sham group.</p>", "links"=>[], "tags"=>["Animal Models Robust", "intramyocardial injection", "Conclusions Animal models", "therapy", "artery", "PBS", "NOD", "MI", "Background Human mesenchymal stromal cells", "function", "ligation", "iMSC", "MSC", "Experimental Human Mesenchymal Stromal Cell Therapy", "uMSC"], "article_id"=>3162634, "categories"=>["Biophysics", "Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Biotechnology", "Immunology", "Developmental Biology", "Cancer", "Hematology", "Infectious Diseases"], "users"=>["Melina C. den Haan", "Vanessa-Leigh van Zuylen", "Niek J. Pluijmert", "Cindy I. Schutte", "Willem E. Fibbe", "Martin J. Schalij", "Helene Roelofs", "Douwe E. Atsma"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0152938.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Flow_cytometric_analysis_of_inflammatory_cells_in_the_heart_15_days_after_myocardial_infarction_in_uMSC_and_iMSC_treated_animals_uMSC_and_iMSC_resp_PBS_treated_animals_PBS_and_Sham_operated_animals_Sham_/3162634", "title"=>"Flow cytometric analysis of inflammatory cells in the heart 15 days after myocardial infarction in uMSC and iMSC treated animals (uMSC and iMSC, resp.), PBS treated animals (PBS) and Sham-operated animals (Sham).", "pos_in_sequence"=>7, "defined_type"=>1, "published_date"=>"2016-04-06 04:58:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/4925278"], "description"=>"<p>A: From left to right: Immunostaining of iMSCs for HLA-DR in red (PE) and nuclei in blue (DAPI) and expression of HLA-DR as measured by flow cytometry. B: Immunostaining of iMSCs for the immunomodulatory enzyme IDO in green (ALEXA 488 nm) and nuclei in blue (DAPI).</p>", "links"=>[], "tags"=>["Animal Models Robust", "intramyocardial injection", "Conclusions Animal models", "therapy", "artery", "PBS", "NOD", "MI", "Background Human mesenchymal stromal cells", "function", "ligation", "iMSC", "MSC", "Experimental Human Mesenchymal Stromal Cell Therapy", "uMSC"], "article_id"=>3162487, "categories"=>["Biophysics", "Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Biotechnology", "Immunology", "Developmental Biology", "Cancer", "Hematology", "Infectious Diseases"], "users"=>["Melina C. den Haan", "Vanessa-Leigh van Zuylen", "Niek J. Pluijmert", "Cindy I. Schutte", "Willem E. Fibbe", "Martin J. Schalij", "Helene Roelofs", "Douwe E. Atsma"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0152938.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Stimulation_of_MSCs_with_the_pro_inflammatory_cytokine_interferon_gamma_IFN_/3162487", "title"=>"Stimulation of MSCs with the pro-inflammatory cytokine interferon gamma (IFN).", "pos_in_sequence"=>3, "defined_type"=>1, "published_date"=>"2016-04-06 04:58:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/4925371"], "description"=>"<p>A: Immunofluorescent staining of engrafted eGFP-labeled MSCs in red (Qdot 655) and nuclei in blue (hoechst 33342). B: Histological quantification of uMSC and iMSC engraftment (uMSC and iMSC resp.). PBS treated animals (PBS) and Sham-operated animals (Sham) were used as controls. C: Quantitative PCR for human genomic DNA in mouse hearts in animals treated with uMSC, iMSC, PBS and sham-operated animals. Data are expressed as mean ± SD. There were no significant differences between the uMSC and iMSC group.</p>", "links"=>[], "tags"=>["Animal Models Robust", "intramyocardial injection", "Conclusions Animal models", "therapy", "artery", "PBS", "NOD", "MI", "Background Human mesenchymal stromal cells", "function", "ligation", "iMSC", "MSC", "Experimental Human Mesenchymal Stromal Cell Therapy", "uMSC"], "article_id"=>3162574, "categories"=>["Biophysics", "Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Biotechnology", "Immunology", "Developmental Biology", "Cancer", "Hematology", "Infectious Diseases"], "users"=>["Melina C. den Haan", "Vanessa-Leigh van Zuylen", "Niek J. Pluijmert", "Cindy I. Schutte", "Willem E. Fibbe", "Martin J. Schalij", "Helene Roelofs", "Douwe E. Atsma"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0152938.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Assessment_of_engraftment_of_injected_MSCs_in_mouse_hearts_15_days_after_injection_into_the_infarcted_myocardium_/3162574", "title"=>"Assessment of engraftment of injected MSCs in mouse hearts 15 days after injection into the infarcted myocardium.", "pos_in_sequence"=>5, "defined_type"=>1, "published_date"=>"2016-04-06 04:58:51"}

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Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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