Smoking and Diabetes Attenuate Number of CD34+ Haematopoietic Stem Cells in Peripheral Blood of Patients with Advanced Peripheral Artery Disease (original) (raw)
Related papers
Transfusion Medicine and Hemotherapy, 2009
Background: The number of primitive progenitor cells (pPC) in healthy individuals, in correlation to age, gender, and smoking status, has not yet been thoroughly elucidated. Material and Methods: The pPC from a collective of 168 healthy blood donors aged 18-61 years was investigated using flow cytometric analysis. In addition, the pPC of 20 subjects were studied once a month for half a year to determine the extent of physiological variation of pPC within a single individual. Results: We demonstrated a statistically significant difference (p = 0.005) in the numbers of pPC in men (836,100/l) versus women (583,850/l). No statistical difference was found between younger and older donors or between smokers and non-smokers, both overall and within a single gender. The extent of physiological variation in pPC was lower than 20% in 2 individuals, 18 individuals exhibited amplitudes greater than 20%. Conclusion: We conclude that the number of pPC in healthy individuals was primarily determined by gender as an operative factor. It seems that age and smoking status are of minor importance. Furthermore, our data demonstrate strong variability in the expression of pPC within a single individual. This may be influenced by varying physiological and environmental factors.
International Journal of Stem Cells, 2021
Diabetes mellitus (DM) remains one of the most important risk factors for peripheral artery disease (PAD), with approximately 20% of DM patients older than 40 years old are affected with PAD. The current standard management for severe PAD is endovascular intervention with or without surgical bypass. Unfortunately, up to 40% of patients are unable to undergo these revascularization therapies due to excessive surgical risk or adverse vascular side effects. Stem cell therapy has emerged as a novel therapeutic strategy for these 'no-option' patients. Several types of stem cells are utilized for PAD therapy, including bone marrow mononuclear cells (BMMNC) and peripheral blood mononuclear cells (PBMNC). Many studies have reported the safety of BMMNC and PBMNC, as well as its efficacy in reducing ischemic pain, ulcer size, pain-free walking distance, ankle-brachial index (ABI), and transcutaneous oxygen pressure (TcPO2). However, the capacity to establish the efficacy of reducing major amputation rates, amputation free survival, and all-cause mortality is limited, as shown by several randomized placebo-controlled trials. The present literature review will focus on comparing safety and efficacy between BMMNC and PBMNC as cell-based management in diabetic patients with PAD who are not suitable for revascularization therapy.
The Role of the Stem Cells Therapy in the Peripheral Artery Disease
International Journal of Molecular Sciences
Vascular complications of diabetes mellitus are an important issue for all clinicians involved in the management of this complex pathology. Although many therapeutic advances have been reached, peripheral arterial disease is still an unsolved problem that each year compromises the quality of life and life span of affected patients. Oftentimes, patients, after ineffective attempts of revascularization, undergo greater amputations. At the moment, there is no effective and definitive treatment available. In this scenario, the therapeutic use of stem cells could be an interesting option. The aim of the present review is to gather all the best available evidence in this regard and to define a new role of the stem cells therapy in this field, from biomarker to possible therapeutic target.
PLOS ONE
Circulating angiogenic cells (CACs) of various described phenotypes participate in the regeneration of the damaged endothelium, but the abundance of these cells is highly influenced by external cues including diabetes. It is not entirely clear which CAC populations are most reflective of endothelial function nor which are impacted by diabetes. To answer these questions, we enrolled a human cohort with variable CVD risk and determined relationships between stratified levels of CACs and indices of diabetes and vascular function. We also determined associations between CAC functional markers and diabetes and identified proangiogenic molecules which are impacted by diabetes. We found that subjects with low levels of CD34 + /AC133 + /CD31 + /CD45 dim cells (CAC-3) had a significantly higher incidence of diabetes (p = 0.004), higher HbA1c levels (p = 0.049) and higher CVD risk scores. Furthermore, there was an association between low CAC-3 levels and impaired vascular function (p = 0.023). These cells from diabetics had reduced levels of CXCR4 and VEGFR2, while diabetics had higher levels of certain cytokines and pro-angiogenic molecules. These results suggest that quantitative and functional defects of CD34 + /AC133 + /CD31 + /CD45 dim cells are associated with diabetes and vascular impairment and that this cell type may be a prognostic indicator of CVD and vascular dysfunction.
Circulation, 2017
Background -Atherosclerotic peripheral artery disease (PAD) affects 8-12% of Americans over 65 and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE is an NHLBI-sponsored, randomized, double-blind, placebo-controlled phase 2, exploratory clinical trial designed to assess safety and efficacy of autologous bone marrow-derived aldehyde dehydrogenase bright (ALDHbr) cells in PAD patients and to explore associated claudication physiologic mechanisms. Methods -All participants, randomized 1:1 to receive ALDHbr cells or placebo, underwent bone marrow aspiration and isolation of ALDHbr cells, followed by ten injections into the thigh and calf of the index leg. The co-primary endpoints were: change from baseline to six months in peak walking time (PWT), collateral count, peak hyperemic popliteal flow, and capillary perfusion ...
Angiogenesis
Lower numbers of progenitor cells (PCs) in peripheral blood (PB) have been associated with cardiovascular events in highrisk populations. Therapies aiming to increase the numbers of PCs in circulation have been developed, but clinical trials did not result in better outcomes. It is currently unknown what causes the reduction in PB PC numbers: whether it is primary depletion of the progenitor cell reserve, or a reduced mobilization of PCs from the bone marrow (BM). In this study, we examine if PB and BM PC numbers predict Amputation-Free Survival (AFS) in patients with Severe Limb Ischemia (SLI). We obtained PB and BM from 160 patients enrolled in a clinical trial investigating BM cell therapy for SLI. Samples were incubated with antibodies against CD34, KDR, CD133, CD184, CD14, CD105, CD140b, and CD31; PC populations were enumerated by flow cytometry. Higher PB CD34 + and CD133 + PC numbers were related to AFS (Both Hazard Ratio [HR event ] = 0.56, p = 0.003 and p = 0.0007, respectively). AFS was not associated with the other cell populations in PB. BM PC numbers correlated with PB PC numbers and showed similar HRs for AFS. A further subdivision based on relative BM and PB PC numbers showed that BM PC numbers, rather than mobilization, associated with AFS. Both PB and BM PC numbers are associated with AFS independently from traditional risk factor and show very similar risk profiles. Our data suggest that depletion of the progenitor cell reserve, rather than decreased PC mobilization, underlies the association between PB PC numbers and cardiovascular risk.
Vascular medicine (London, England), 2006
To determine whether exercise increases endothelial progenitor cells (EPCs) in patients with peripheral vascular disease, we developed a multi-parameter flow cytometry assay to rigorously assess EPCs and mature endothelial cells (ECs) in control subjects and patients with peripheral artery disease (PAD) subjected to graded exercise. Blood was collected from young healthy subjects (n = 9, mean age 33 years), older healthy subjects (n = 13, mean age 66 years), and older subjects with PAD (n = 15, mean age 69 years) before and 10 minutes after exercise. White blood cells were isolated and stained with a five-color antibody panel: FITC-anti-CD31, PE-anti-CD146, PE-anti-CD133, PerCP-Cy5.5-anti-CD3,-CD19,-CD33, PE-Cy7-anti-CD34, and APC-anti-VEGF-R2. Viability was assessed by propidium iodide exclusion. Viable, low, side scatter singlets that were CD3-, 19-, and 33-negative were counted. While baseline levels of EPCs and ECs were similar among all subjects, young healthy subjects demonstr...
Cytotherapy, 2010
Background aims-The distinction between hematopoietic stem cells (HSC) and endothelial progenitor cells (EPC) is poorly defined. Co-expression of CD34 antigen with vascular endothelial growth factor (VEGF) receptor (VEGFR2) is currently used to define EPC (1). Methods-We evaluated the phenotypic and genomic characteristics of peripheral blood-derived CD34 + cells in 22 granulocyte-colony-stimulating factor (G-CSF)-mobilized patients with severe coronary artery disease and assessed the influence of cell selection and storage on CD34 + cell characteristics. Results-The median CD34 + cell contents in the products before and after enrichment with the Isolex 300i Magnetic Cell Selection System were 0.2% and 82.5%, respectively. Cell-cycle analysis showed that 80% of CD34 + cells were in G0 stage; 70% of the isolated CD34 + cells coexpressed CD133, a marker for more immature progenitors. However, less than 5% of the isolated CD34 + cells co-expressed the notch receptor Jagged-1 (CD339) and only 2% of the isolated CD34 + population were positive for VEGFR2 (CD309). Molecular assessment of the isolated CD34 + cells demonstrated extremely low expression of VEGFR2 and endothelial nitric oxide synthase (eNOS) and high expression of VEGF-A. Overnight storage at 4°C did not significantly affect CD34 + cell counts and viability. Storage in liquid nitrogen for 7 weeks did not affect the percentage of CD34 + cells but was associated with a 26% drop in cell viability. Conclusions-We have demonstrated that the majority of isolated CD34 + cells consist of immature and quiescent cells that lack prototypic markers of EPC. High VEGF-A gene expression might be one of the mechanisms for CD34 + cell-induced angiogenesis.
THE IMPACT OF DIABETES ON PERIVASCULAR STEM CELL NICHE OF THE BONE MARROW
Recent studies are mainly focused on the adverse effect of Diabetes Mellitus on the bone marrow stem cells. It has been demonstrated that diabetes causes microvascular complications in the bone marrow vasculature leading to micro-angiopathies. Our study was mainly focused on the impact of diabetes on the perivascular cells of the bone marrow stem cell niche. We were interested in three perivascular stem cell subtypes, CD146+, CD146- and Mesenchymal Stem Cells (MSCs). The subtypes of cells were successfully isolated from bone marrow biopsies of diabetic and healthy individuals and then successfully expanded in ex vivo condition. The subtypes were then characterized for specific markers by immunocytochemistry. After reaching enough confluence, each subtype cell lines (diabetic and healthy) were conditioned for 24hrs in different media containing different glucose concentration ranging from normal glucose, NG, (5mM) to high glucose, HG, (15 mM and 30 mM). Functionality assays (Viability, Proliferation, Apoptosis, and Migration) were carried out on the cells and the results were interpreted statistically (two way ANOVA, Bonferroni t-test) in the form of bar-graphs (CTRL Vs Diabetic and NG Vs HG). The results demonstrated that diabetes has an alarming impact on CD146+ in term of viability, proliferation and migration in comparison with the diabetic CD146- and MSCs. Data from HG model also point out that HG has an impact on the cellular functions of the healthy cell subtypes as well as the diabetic counterparts, reducing the viability, proliferation and apoptosis mainly.
Background: Quality and Quantity (QQ) culture media was shown a promising effect in enhancing the vasculogenesis of mononuclear cells (MNCs) of healthy volunteers and chronic limb-threatening ischemia (CLTI) patients. In this study, the MNCs from CLTI patients were further investigated based of their risk factors. Methods: In this study, MNCs from chronic limb-threatening ischemia (CLTI) patients with coexisting diabetes mellitus (DM), hypertension (HT), current smoker status, or chronic kidney disease (CKD) stage 3 or above were cultured in QQ culture media, and then investigated for angiogenesis-related phenotype and function. CLTI patients with DM, HT, current smoker status, or CKD were prospectively recruited. Forty-eight patients (mean age: 67.5±8.0 years) were included. DM, HT, current smoker status, and CKD was found in 34 (71.0%), 39 (81.0%), 27(56.3%), and 32 (66.7%) patients, respectively. Results: In CLI patients with coexisting diseases, the percentages of CD34+, CD133+,...