ArticlePloS one2013
Bone marrow alterations and lower endothelial progenitor cell numbers in critical limb ischemia patients.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Patients With Chronic Critical Limb Ischemia: a Randomized, Placebo-controlled Clinical Trial
Allogeneic Mesenchymal Stromal Cells for Angiogenesis and Neovascularization in No-option Ischemic Limbs; A Double-blind, Randomized, Placebo-controlled Trial
Who cites it
30 citing papers in PubMed, 67 citations in OpenAlex.
- Autologous Granulocyte Colony-Stimulating Factor-Mobilized Peripheral Blood CD34 Positive Cell Transplantation for Hemodialysis Patients with Critical Limb Ischemia: A Prospective Phase II Clinical Trial.Stem cells translational medicine · 2018Trial
- Trial
- Unraveling the differential mechanisms of revascularization promoted by MSCs & ECFCs from adipose tissue or umbilical cord in a murine model of critical limb-threatening ischemia.Journal of biomedical science · 2024Article
- Nailfold Capillaroscopy: A Comprehensive Review on Its Usefulness in Both Clinical Diagnosis and Improving Unhealthy Dietary Lifestyles.Nutrients · 2024Review
- Therapeutic angiogenesis for patients with chronic limb-threatening ischemia: promising or hoax?Vascular biology (Bristol, England) · 2024Review
- Platelet-Derived Growth Factor-BB Priming Enhances Vasculogenic Capacity of Bone Marrow-Derived Endothelial Precursor Like Cells.Tissue engineering and regenerative medicine · 2023Article
- Repair of Limb Ischemia Is Dependent on Hematopoietic Stem Cell Specific-SHP-1 Regulation of TGF-β1.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy.Stem cell research & therapy · 2021Article
- Advances of Endothelial Progenitor Cells in the Development of Depression.Frontiers in cellular neuroscience · 2021Review
- Induced endothelial cells from peripheral arterial disease patients and neonatal fibroblasts have comparable angiogenic properties.PloS one · 2021Article
- A Pro-Inflammatory Biomarker-Profile Predicts Amputation-Free Survival in Patients with Severe Limb Ischemia.Scientific reports · 2019Article
- Bone marrow derived endothelial progenitor cells retain their phenotype and functions after a limited number of culture passages and cryopreservation.Cytotechnology · 2019Article
- Mesenchymal Stromal Cell Characteristics and Regenerative Potential in Cardiovascular Disease: Implications for Cellular Therapy.Cell transplantation · 2018Review
- Autologous Stem Cell Therapy in Critical Limb Ischemia: A Meta-Analysis of Randomized Controlled Trials.Stem cells international · 2018Review
- Endothelial Regenerative Capacity and Aging: Influence of Diet, Exercise and Obesity.Current cardiology reviews · 2018Review
- Chronic Psychological Stress Accelerates Vascular Senescence and Impairs Ischemia-Induced Neovascularization: The Role of Dipeptidyl Peptidase-4/Glucagon-Like Peptide-1-Adiponectin Axis.Journal of the American Heart Association · 2017Article
- Safety and Effectiveness of Bone Marrow Cell Concentrate in the Treatment of Chronic Critical Limb Ischemia Utilizing a Rapid Point-of-Care System.Stem cells international · 2017Article
- Cell Therapy and Critical Limb Ischemia: Evidence and Window of Opportunity in Obesity.Obesity & control therapies : open access · 2016Article
- Vascular Ageing and Exercise: Focus on Cellular Reparative Processes.Oxidative medicine and cellular longevity · 2016Review
- tPA-MMP-9 Axis Plays a Pivotal Role in Mobilization of Endothelial Progenitor Cells from Bone Marrow to Circulation and Ischemic Region for Angiogenesis.Stem cells international · 2016Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCritical limb ischemia (CLI) is characterized by lower extremity artery obstruction and a largely unexplained impaired ischemic neovascularization response. Bone marrow (BM) derived endothelial progenitor cells (EPC) contribute to neovascularization. We hypothesize that reduced levels and function of circulating progenitor cells and alterations in the BM contribute to impaired neovascularization in CLI.
methodsLevels of primitive (CD34(+) and CD133(+)) progenitors and CD34(+)KDR(+) EPC were analyzed using flow cytometry in blood and BM from 101 CLI patients in the JUVENTAS-trial (NCT00371371) and healthy controls. Blood levels of markers for endothelial injury (sE-selectin, sICAM-1, sVCAM-1, and thrombomodulin), and progenitor cell mobilizing and inflammatory factors were assessed by conventional and multiplex ELISA. BM levels and activity of the EPC mobilizing protease MMP-9 were assessed by ELISA and zymography. Circulating angiogenic cells (CAC) were cultured and their paracrine function was assessed.
resultsEndothelial injury markers were higher in CLI (P<0.01). CLI patients had higher levels of VEGF, SDF-1α, SCF, G-CSF (P<0.05) and of IL-6, IL-8 and IP-10 (P<0.05). Circulating EPC and BM CD34(+) cells (P<0.05), lymphocytic expression of CXCR4 and CD26 in BM (P<0.05), and BM levels and activity of MMP-9 (P<0.01) were lower in CLI. Multivariate regression analysis showed an inverse association between IL-6 and BM CD34(+) cell levels (P = 0.007). CAC from CLI patients had reduced paracrine function (P<0.0001).
conclusionCLI patients have reduced levels of circulating EPC, despite profound endothelial injury and an EPC mobilizing response. Moreover, CLI patients have lower BM CD34(+)-cell levels, which were inversely associated with the inflammatory marker IL-6, and lower BM MMP-9 levels and activity. The results of this study suggest that inflammation-induced BM exhaustion and a disturbed progenitor cell mobilization response due to reduced levels and activity of MMP-9 in the BM and alterations in the SDF-1α/CXCR4 interaction contribute to the attenuated neovascularization in CLI patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.