Circulating haematopoietic stem cells and long-term outcomes of COVID-19.

Background And Aims: An acute depletion of circulating haematopoietic stem/progenitor cells (HSPCs) occurs during COVID-19, especially among patients with a poorer disease course. We herein examined whether HSPCs levels at hospital admission for COVID-19 predict 1-year mortality and the long-COVID syndrome.

Materials And Methods: Patients hospitalized for COVID-19 in an infectious disease ward were consecutively enrolled.

Improved prediction of long-term kidney outcomes in people with type 2 diabetes by levels of circulating haematopoietic stem/progenitor cells.

Aim/hypothesis: We examined whether prediction of long-term kidney outcomes in individuals with type 2 diabetes can be improved by measuring circulating levels of haematopoietic stem/progenitor cells (HSPCs), which are reduced in diabetes and are associated with cardiovascular risk.

Methods: We included individuals with type 2 diabetes who had a baseline determination of circulating HSPCs in 2004-2019 at the diabetes centre of the University Hospital of Padua and divided them into two groups based on their median value per ml of blood. We collected updated data on eGFR and albuminuria up to December 2022.

Hematopoietic Stem Cells and Metabolic Deterioration in Alström Syndrome, a Rare Genetic Model of the Metabolic Syndrome.

Alström syndrome (AS) is a rare genetic disease caused by ALMS1 mutations, characterized by short stature, and vision and hearing loss. Patients with AS develop the metabolic syndrome, long-term organ complications, and die prematurely. We explored the association between AS and a shortage of hematopoietic stem/progenitor cells (HSPCs), which is linked to metabolic diseases and predicts diabetic complications.

A miR-125/Sirtuin-7 pathway drives the pro-calcific potential of myeloid cells in diabetic vascular disease.

Aims/hypothesis: Ectopic calcification is a typical feature of diabetic vascular disease and resembles an accelerated ageing phenotype. We previously found an excess of myeloid calcifying cells in diabetic individuals. We herein examined molecular and cellular pathways linking atherosclerotic calcification with calcification by myeloid cells in the diabetic milieu.

Hematopoietic progenitor cell liabilities and alarmins S100A8/A9-related inflammaging associate with frailty and predict poor cardiovascular outcomes in older adults.

Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular disease and death. The mechanisms linking frailty and cardiovascular outcomes are mostly unknown. Here, we studied the association of abundance (flow cytometry) and gene expression profile (RNAseq) of stem/progenitor cells (HSPCs) and molecular markers of inflammaging (ELISA) with the cardiorespiratory phenotype and prospective adverse events of individuals classified according to levels of frailty.

Inhibition of SGLT2 Rescues Bone Marrow Cell Traffic for Vascular Repair: Role of Glucose Control and Ketogenesis.

The mechanisms by which sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in people with diabetes are incompletely understood. Recent studies show that SGLT2i may increase the levels of circulating cells with vascular regenerative capacity, at least in part by lowering glycemia. In this study, we used mice with streptozotocin-induced diabetes treated with the SGLT2i dapagliflozin at a dose that reduced glucose levels by 20%.

Stem cell mobilization with plerixafor and healing of diabetic ischemic wounds: A phase IIa, randomized, double-blind, placebo-controlled trial.

Bone marrow-derived cells contribute to tissue repair, but traffic of hematopoietic stem/progenitor cells (HSPCs) is impaired in diabetes. We therefore tested whether HSPC mobilization with the CXCR4 antagonist plerixafor improved healing of ischemic diabetic wounds. This was a pilot, phase IIa, double-blind, randomized, placebo-controlled trial (NCT02790957).

Pharmacologic PPAR-γ Activation Reprograms Bone Marrow Macrophages and Partially Rescues HSPC Mobilization in Human and Murine Diabetes.

Mobilization of hematopoietic stem/progenitor cells (HSPC) from the bone marrow (BM) is impaired in diabetes. Excess oncostatin M (OSM) produced by M1 macrophages in the diabetic BM signals through p66Shc to induce in stromal cells and retain HSPC. BM adipocytes are another source of CXCL12 that blunts mobilization.

Diabetes mellitus impairs circulating proangiogenic granulocytes.

Aims/hypothesis: Cardiovascular risk in diabetes is at least in part attributable to defective angiogenesis. Since diabetes negatively affects blood cells involved in angiogenesis, we herein evaluated whether diabetes impairs proangiogenic granulocytes (PAGs).

Methods: We characterised and quantified PAGs as CD49d granulocytes in peripheral blood of participants with type 2 or type 1 diabetes and in non-diabetic control participants.

Activation profiles of monocyte-macrophages and HDL function in healthy women in relation to menstrual cycle and in polycystic ovary syndrome patients.

Purpose: Hormonal status and menopause affect human macrophage function and cardiometabolic risk. In polycystic ovary syndrome (PCOS) patients the cardiometabolic risk increases through mechanisms that are largely unknown. We tested the hypotheses that macrophage activation is influenced by menstrual cycle and that ovarian dysfunction in PCOS patients is associated with altered macrophage inflammatory responses and cholesterol efflux capacity of serum HDL.

Effects of SGLT2 Inhibitors on Circulating Stem and Progenitor Cells in Patients With Type 2 Diabetes.

Context: Reduction in the levels of circulating stem cells (CSCs) and endothelial progenitor cells (EPCs) predicts development or progression of microangiopathy and macroangiopathy in patients with type 2 diabetes (T2D).

Objective: We tested whether treatment with sodium glucose cotransporter-2 (SGLT2) inhibitors affected the levels of CSCs and EPCs.

Design: A randomized trial of dapagliflozin vs placebo with open-label extension, and an open-label observational study of empagliflozin treatment.

The continuum of monocyte phenotypes: Experimental evidence and prognostic utility in assessing cardiovascular risk.

The monocyte-macrophage cell lineage represents a major player in innate immunity, and is involved in many physiologic and pathologic conditions. Particularly, monocyte-macrophages play a very important role in atherosclerosis and cardiovascular disease. Monocyte heterogeneity is well recognized but the biologic and clinical meaning of the various monocyte subtypes is not entirely understood.

The antidiabetic drug metformin blunts NETosis in vitro and reduces circulating NETosis biomarkers in vivo.

Aims: Diabetes is associated with an excess release of neutrophil extracellular traps (NETs) and an enhanced NETosis, a neutrophil cell death programme instrumental to anti-microbial defences, but also involved in tissue damage. We herein investigated whether the antidiabetic drug metformin protects against NETosis.

Methods: We measured NET components in the plasma of patients with pre-diabetes who were randomized to receive metformin or placebo for 2 months.

Shift of monocyte subsets along their continuum predicts cardiovascular outcomes.

Background And Aims: Distribution of monocyte subsets has been shown to predict cardiovascular outcomes. However, monocytes form a continuum and categorization into discrete subsets may be an oversimplification. We herein aimed at establishing whether distribution of monocytes based on CD14 and CD16 fluorescence intensity provides incremental and complementary information on cardiovascular outcomes beyond enumeration of traditional subsets.

Persistent Reduction of Circulating Myeloid Calcifying Cells in Acromegaly: Relevance to the Bone-Vascular Axis.

Context: Acromegaly is a systemic disease characterized by persistent bone pathology and excess cardiovascular mortality. Despite multiple concomitant risk factors, atherosclerosis does not seem to be accelerated in acromegaly.

Objective: To compare the levels of circulating myeloid calcifying cells (MCCs), which promote ectopic calcification and inhibit angiogenesis, in individuals with and without acromegaly.

Long-term Prediction of Cardiovascular Outcomes by Circulating CD34+ and CD34+CD133+ Stem Cells in Patients With Type 2 Diabetes.

Objective: Cardiovascular risk varies substantially in the population with diabetes, and biomarkers can improve risk stratification. Circulating stem cells predict future cardiovascular events and death, but data for the population with diabetes are scant. In this study we evaluated the ability of circulating stem cell levels to predict future cardiovascular outcomes and improve risk discrimination in patients with type 2 diabetes.

Plerixafor improves the endothelial health balance. The effect of diabetes analysed by polychromatic flow cytometry.

Background And Aims: Diabetes damages the endothelium and reduces the availability of bone marrow (BM)-derived endothelial progenitor cells (EPCs). The mobilization of hematopoietic stem cells (HSCs) and EPCs in response to G-CSF is impaired by diabetes, owing to CXCL12 dysregulation. We have previously shown that the CXCR4/CXCL12 disruptor plerixafor rescues HSC and EPC mobilization in diabetes.

NETosis Delays Diabetic Wound Healing in Mice and Humans.

Upon activation, neutrophils undergo histone citrullination by protein arginine deiminase (PAD)4, exocytosis of chromatin and enzymes as neutrophil extracellular traps (NETs), and death. In diabetes, neutrophils are primed to release NETs and die by NETosis. Although this process is a defense against infection, NETosis can damage tissue.

Acute Effects of Linagliptin on Progenitor Cells, Monocyte Phenotypes, and Soluble Mediators in Type 2 Diabetes.

Context: Circulating cells, including endothelial progenitor cells (EPCs) and monocyte subtypes, are involved in diabetic complications. Modulation of these cells may mediate additional benefits of glucose-lowering medications.

Objective: We assessed whether the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin acutely modifies EPCs and monocyte subsets in patients with type 2 diabetes.

Circulating Stem Cells Associate With Adiposity and Future Metabolic Deterioration in Healthy Subjects.

Context: Obesity and metabolic syndrome are associated with mild leukocytosis, but whether hematopoietic stem/progenitor cells (HSPCs) play a role in metabolic deterioration is unknown.

Objective: Our objective was to analyze the cross-sectional and longitudinal associations between CD34(+) HSPCs, adiposity, and metabolic syndrome features.

Design: This is a cross-sectional study on 242 participants, 155 of whom were followed and included in a longitudinal assessment.