Progenitor Cells In Subjects Research Articles

Adjuvant Treatment with Empagliflozin or Semaglutide Increases Endothelial Progenitor Cells in Subjects with Well-Controlled Type 1 Diabetes Mellitus.

Circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) are promising markers of vascular damage and endothelial regeneration potential. We focused on the detection of CECs and EPCs using flow cytometry with regard to analytical challenges and its suitability for routine testing. As part of a clinical validation, CECs and EPCs were measured in blood samples from 83 subjects with type 1 diabetes (T1DM), evaluating an adjuvant intervention with two different antidiabetic drugs, empagliflozin (N = 28) and semaglutide (N = 29). Both groups receiving adjuvant therapy were compared with the insulin-only group (N = 26) at two time points: before the start of therapy and after 12 weeks of adjuvant therapy. All three groups were comparable regarding demographic characteristics and concomitant risk factors. Absolute and relative endothelial cell count at baseline were low and comparable to those of healthy individuals. In the group receiving empagliflozin or semaglutide, a significant increase in EPC was observed after 12 weeks of treatment. We demonstrated that EPCs have the potential to serve as markers for monitoring the efficacy of adjuvant therapy in T1DM patients. However, before their implementation in clinical practice, the flow cytometry protocol for CEC and EPC identification and quantification must be standardized.

Reassessing the effects of continuous positive airway pressure (CPAP) on arterial stiffness and peripheral blood derived CD34+ progenitor cells in subjects with sleep apnea

BackgroundObstructive sleep apnea (OSA) is an independent risk factor for cardiovascular diseases (CVD) and vascular health. Peripheral blood-derived CD34+ progenitor cells have been used as biomarker for CVD risk and may play a similar role in OSA and CVD risk assessment. Although there are some controversial results in the literature, OSA patients may have a reduction in the number and function of CD34+ cells. The damages promoted by OSA in CD34+ cells may lead to an increase in endothelial oxidative stress and endothelial inflammation which may lead to a reduced endothelial repair capacity. In this study, we explored the effect of continuous positive airway pressure (CPAP) on peripheral blood-derived CD34+ cells and arterial stiffness (another predictor of endothelial health and CVD risk) in OSA patients.Methods and resultsNine overweight and obese subjects without prediabetes or diabetes were recruited. Eight out of nine subjects had moderate to severe degree of OSA. CD34+ cells were isolated from peripheral blood. Number and function of these cells were monitored before and after 3 months of treatment with CPAP. No significant changes were observed in the number of CD34+ cells, CFU-Hill’s colony formation unit (CFU) count or migratory response to the chemotactic factor SDF-1a after CPAP use. However, CXCR4 mRNA expression significantly increased by 2.2-fold indicating that CPAP may have a positive effect on SDF1a receptor (CXCR4), thereby improving migration of CD34+ cells mediated by SDF1a after the 3 month period. Interestingly, in clinical arena our results showed a reduction of pulse wave velocity (an established parameter of arterial stiffness) following CPAP therapy.ConclusionsOur findings suggest that 3-month CPAP intervention does not show statistical significant increase in CD34+ cell number and function, in mostly moderate to severe OSA subjects; however, it did demonstrate a positive trend. CPAP therapy, did help improve arterial stiffness parameter.

Exercise training improves in vivo endothelial repair capacity of early endothelial progenitor cells in subjects with metabolic syndrome

Endothelial dysfunction and injury are considered to contribute considerably to the development and progression of atherosclerosis. It has been suggested that intense exercise training can increase the number and angiogenic properties of early endothelial progenitor cells (EPCs). However, whether exercise training stimulates the capacity of early EPCs to promote repair of endothelial damage and potential underlying mechanisms remain to be determined. The present study was designed to evaluate the effects of moderate exercise training on in vivo endothelial repair capacity of early EPCs, and their nitric oxide and superoxide production as characterized by electron spin resonance spectroscopy analysis in subjects with metabolic syndrome. Twenty-four subjects with metabolic syndrome were randomized to an 8 weeks exercise training or a control group. Superoxide production and nitric oxide (NO) availability of early EPCs were characterized by using electron spin resonance (ESR) spectroscopy analysis. In vivo endothelial repair capacity of EPCs was examined by transplantation into nude mice with defined carotid endothelial injury. Endothelium-dependent, flow-mediated vasodilation was analysed using high-resolution ultrasound. Importantly, exercise training resulted in a substantially improved in vivo endothelial repair capacity of early EPCs (24.0 vs 12.7%; p < 0.05) and improved endothelium-dependent vasodilation. Nitric oxide production of EPCs was substantially increased after exercise training, but not in the control group. Moreover, exercise training reduced superoxide production of EPCs, which was not observed in the control group. The present study suggests for the first time that moderate exercise training increases nitric oxide production of early endothelial progenitor cells and reduces their superoxide production. Importantly, this is associated with a marked beneficial effect on the in vivo endothelial repair capacity of early EPCs in subjects with metabolic syndrome.

Decreased number and impaired functionality of endothelial progenitor cells in subjects with metabolic syndrome: Implications for increased cardiovascular risk

ObjectiveMetabolic syndrome (MetS) is characterized by low-grade inflammation and confers an increased risk for cardiovascular disease. Endothelial progenitor cells (EPCs) are a measure of vascular health and are decreased in patients with various risk factors for cardiovascular disease (CVD). There is a paucity of data examining the EPC status especially in terms of their functionality in MetS subjects without diabetes or cardiovascular disease. We aimed to enumerate and functionally characterize EPCs in subjects with MetS in comparison to healthy controls. MethodsThe study was performed at the University of California Davis Medical Center. Healthy controls (n=31) and MetS (n=46) subjects were included in the study. EPCs were enumerated in fasting blood by KDR/CD34 dual positivity. Functionality was assessed by the colony forming units (CFU) assay, migration and tubule formation. ResultsSubjects with MetS had significantly decreased number of EPCs compared to control subjects. Furthermore, EPCs from MetS subjects depicted significantly impaired clonogenic capacity, i.e., decreased colony forming units, and impaired capacity to incorporate into tubular structures suggesting functional impairment of EPCs from MetS subjects. ConclusionsWe make the novel observation that MetS subjects without diabetes or CVD have decreased EPC number and impaired functionality as compared to control subjects. These findings could contribute to the increased CV risk in this population.

Increased levels of circulating endothelial progenitor cells in subjects with moderate to severe chronic periodontitis

Emerging evidence shows that periodontal disease is associated with endothelial dysfunction. The purpose of this study was to determine the association between chronic periodontitis (CP) and circulating endothelial progenitor cells (EPC). Eighty-six non-smoking subjects (36 males and 50 females, aged 35-80 years) were recruited, including 23 subjects with no or mild CP and 63 subjects with moderate to severe CP. The levels of circulating EPC were quantitatively determined by fluorescence-activated cell analysis, including CD34+/kinase insert domain-containing receptor (KDR)+ (more mature EPC) and CD133+/KDR+ (less mature EPC). Periodontal conditions, the intima-media thickness of carotid arteries and circulating biomarkers were examined. Subjects with moderate to severe CP exhibited an increased risk of high EPC count, compared with those with no or mild CP: CD34+/KDR+ EPC [odds ratio (OR)=9.5, 95% confidence interval (95% CI) 1.5-61.0, p=0.018; CD133+/KDR+ EPC, OR=4.6, 95% CI 1.1-19.5, p=0.039]. C-reactive protein was significantly associated with high CD34+/KDR+ EPC count and age was inversely related with high EPC count. Age, gender and CD34+/KDR+ EPC were independent variables of increased carotid intima-media thickness (p<0.05). This study shows for the first time that moderate to severe CP is associated with an increased level of circulating EPC.

Significance of Endothelial Progenitor Cells in Subjects With Diabetes

Diabetes complications represent a huge burden for patients and health services. The fight against each single complication has led to significant improvements in diabetes care, especially for microvascular complications, yet macroangiopathy remains a major source of morbidity and mortality. A common approach for the prevention and treatment of diabetes complications relies on the understanding of their complex pathophysiology. A unifying biochemical theory suggests that oxidative stress underlies subsequent cellular damage pathways, which leads to diabetes complications, but common supracellular mechanisms are still unclear. Endothelial progenitor cells (EPCs) are circulating immature cells that contribute to vascular homeostasis and compensatory angiogenesis. During the last decade, data have become available indicating that alterations in EPCs may have an important causative role in the development and progression of virtually all diabetes complications. In this review, we will focus on the mechanisms of EPC reduction and dysfunction associated with diabetes by discussing their role in each single complication and possible therapeutic interventions. Diabetes is associated with a unique constellation of disabling complications. While it was originally thought that a single patient tends to develop the cluster of micro- or macrovascular complications, recent prospective studies show that typical markers of microvascular dysfunction, such as microalbuminuria or retinal vascular abnormalities, are associated with an increased risk of macrovascular events (1,2). These and other data suggest that there must be a unifying pathogenetic model underlying diabetes complications. To date, the most credited and supported model proposes that oxidative stress originating from mitochondria activates all subcellular damage pathways (3). However, subsequent events diverge for each complication, and there is not a supracellular unifying hypothesis. The discovery that a subset of circulating immature cells contributes to vascular homeostasis has been a major achievement in many fields of basic science. In this review, we will focus the attention on …

Circulating endothelial progenitor cells in subjects with erectile dysfunction

Erectile dysfunction (ED) is often the first clinical sign of endothelial dysfunction and may precede overt cardiovascular diseases. Bone marrow-derived endothelial progenitor cells migrate into the peripheral circulation to promote endothelial repair. The number of circulating progenitor cells is reduced in patients with cardiovascular risk factor. The objective of our study was to determine the number of these cells in patients with ED both with and without cardiovascular risk factors. These subjects have lower number of circulating progenitor cells, confirming the existence of an endothelial dysfunction and supplying the evidence that ED may be the first symptom of an endothelial damage.