ArticleCirculation research2013
Global remodeling of the vascular stem cell niche in bone marrow of diabetic patients: implication of the microRNA-155/FOXO3a signaling pathway.
Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03260452 (Comparison of Hematopoietic Stem Cell Activity in Adipose Tissue From Type 2 Diabetic Patients and Healthy Volunteers), which is not on this map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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.
Comparison of Hematopoietic Stem Cell Activity in Adipose Tissue From Type 2 Diabetic Patients and Healthy Volunteers: Proof of Concept Study. White Adipose Tissue and Type 2 Diabetes Onset: WAT2DO
Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review.Cardiovascular research · 2016Pooled it
- Phase I/IIa Feasibility Trial of Autologous Quality- and Quantity-Cultured Peripheral Blood Mononuclear Cell Therapy for Non-Healing Extremity Ulcers.Stem cells translational medicine · 2022Trial
- Stem cell mobilization with plerixafor and healing of diabetic ischemic wounds: A phase IIa, randomized, double-blind, placebo-controlled trial.Stem cells translational medicine · 2020Trial
- An unbalanced monocyte polarisation in peripheral blood and bone marrow of patients with type 2 diabetes has an impact on microangiopathy.Diabetologia · 2013Trial
- Shared mechanisms of musculoskeletal dysfunction in type 2 diabetes mellitus: Insights into future therapeutic directions (Review).International journal of molecular medicine · 2026Review
- Resilient Calvarial Bone Marrow Supports Retinal Repair in Type 2 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Broken Cradle: Bone Marrow Stem Cell Niche Remodelling in Diabetes.Stem cell reviews and reports · 2026Review
- Impact of aging on CD146Frontiers in bioengineering and biotechnology · 2026Article
- Bone marrow cellular profile in patients with diabetes: association of statin therapy with CD34+ cells.Frontiers in endocrinology · 2026Observational
- Type 2 diabetes Reprograms Bone Marrow Hematopoiesis and Dysregulates Immune Signaling in Response to Stroke.bioRxiv : the preprint server for biology · 2025Article
- Clinical implications of bone marrow adiposity identified by phenome-wide association and Mendelian randomization in the UK Biobank.Nature communications · 2025Article
- Decreased PECAM-1 May be a potential pathological factor for vascular injury in T2DM patients.Scientific reports · 2025Article
- Function of hematopoiesis and bone marrow niche in inflammation and non-hematopoietic diseases.Life medicine · 2025Review
- Bone Marrow Niche in Cardiometabolic Disease: Mechanisms and Therapeutic Potential.Circulation research · 2025Review
- Prolonged DEHP exposure enhances the stemness and metastatic potential of TNBC cells in an MSI2-dependent manner.International journal of biological sciences · 2025Article
- Adiposity and Mineral Balance in Chronic Kidney Disease.Current osteoporosis reports · 2024Review
- The long-chain polyfluorinated alkyl substance perfluorohexane sulfonate (PFHxS) promotes bone marrow adipogenesis.Toxicology and applied pharmacology · 2024Article
- Function and Regulation of Bone Marrow Adipose Tissue in Health and Disease: State of the Field and Clinical Considerations.Comprehensive Physiology · 2024Review
- The Bone Marrow Microenvironment in Immune-Mediated Inflammatory Diseases: Implications for Mesenchymal Stromal Cell-Based Therapies.Stem cells translational medicine · 2024Review
- Diabetic microvascular disease in non-classical beds: the hidden impact beyond the retina, the kidney, and the peripheral nerves.Cardiovascular diabetology · 2023Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
rationaleThe impact of diabetes mellitus on bone marrow (BM) structure is incompletely understood.
objectiveInvestigate the effect of type-2 diabetes mellitus (T2DM) on BM microvascular and hematopoietic cell composition in patients without vascular complications. METHODS AND
resultsBone samples were obtained from T2DM patients and nondiabetic controls (C) during hip replacement surgery and from T2DM patients undergoing amputation for critical limb ischemia. BM composition was assessed by histomorphometry, immunostaining, and flow cytometry. Expressional studies were performed on CD34(pos) immunosorted BM progenitor cells (PCs). Diabetes mellitus causes a reduction of hematopoietic tissue, fat deposition, and microvascular rarefaction, especially when associated with critical limb ischemia. Immunohistochemistry documented increased apoptosis and reduced abundance of CD34(pos)-PCs in diabetic groups. Likewise, flow cytometry showed scarcity of BM PCs in T2DM and T2DM+critical limb ischemia compared with C, but similar levels of mature hematopoietic cells. Activation of apoptosis in CD34(pos)-PCs was associated with upregulation and nuclear localization of the proapoptotic factor FOXO3a and induction of FOXO3a targets, p21 and p27(kip1). Moreover, microRNA-155, which regulates cell survival through inhibition of FOXO3a, was downregulated in diabetic CD34(pos)-PCs and inversely correlated with FOXO3a levels. The effect of diabetes mellitus on anatomic and molecular end points was confirmed when considering background covariates. Furthermore, exposure of healthy CD34(pos)-PCs to high glucose reproduced the transcriptional changes induced by diabetes mellitus, with this effect being reversed by forced expression of microRNA-155.
conclusionsWe provide new anatomic and molecular evidence for the damaging effect of diabetes mellitus on human BM, comprising microvascular rarefaction and shortage of PCs attributable to activation of proapoptotic pathway.
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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.