Significance of circulating endothelial progenitor cells in patients with fracture healing process.
ABSTRACT Fracture healing is a complex bone formation process, and neovascularization may contribute to new bone regeneration. The circulating endothelial progenitor cell (EPC) mobilization and homing could involve in neovascularization and vasculogenesis. In this study, we investigate the changes of circulating EPC during bone fracture healing, and the possible contribution of EPCs to increased neovascularization and fracture healing. The number of circulating EPCs was monitored in twenty-four patients with long bone traumatic fracture within the first 48 h and at 3, 5, 10, and 14 days post-fracture. The mononuclear cells which isolated from peripheral blood were analyzed by flow cytometry. Peripheral blood counts of leukocytes and platelets were measured by hematology analyzer. The amount of peripheral EPCs significantly increased in patients with fracture compared to age-matched healthy control subjects within the first 48 h after injury, and peaked at 3 days post-fracture. There was no significant difference in the change trend of early EPCs between male and female, but the number of early EPCs was significantly greater in younger patients compared to older patients. A comparison of the EPCs levels between patients with severe injury (ISS > 16) and patients with mild injury (ISS ≤ 16) revealed no statistically significant difference. The level of early EPCs was inverse correlation with the level of plate after fracture, but no correlation with the level of peripheral leucocytes. These findings suggest traumatic fracture may induce the mobilization of EPCs into the peripheral circulation. The increased EPCs may contribute to neovascularization and involve in fracture healing. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1860-1866, 2012.
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ABSTRACT: Failures in fracture healing after conventional autologous and allogenic bone grafting are mainly due to poor vascularization. To meet the clinical demand, recent attentions in the regeneration and repair of bone have been focused on the use of stem cells such as bone marrow mesenchymal stem cells and circulating skeletal stem cells. Circulating stem cells are currently paid a lot of attention due to their ease of clinical setting and high potential for osteogenesis and angiogenesis. In this report, we focus on the first proof-of-principle experiments demonstrating the collaborative characteristics of circulating CD34+ cells, known as endothelial and hematopoietic progenitor cell-rich population, which are capable to differentiate into both endothelial cells and osteoblasts. Transplantation of circulating CD34+ cells provides a favorable environment for fracture healing via angiogenesis/vasculogenesis and osteogenesis, finally leading to functional recovery from fracture. Based on a series of basic studies, we performed a phase 1/2 clinical trial of autologous CD34+ cell transplantation in patients with tibial or femoral nonunions and reported the safety and efficacy of this novel therapy. In this review, the current concepts and strategies in circulating CD34+ cell-based therapy and its potential applications for bone repair will be highlighted.Tissue Engineering Part B Reviews 12/2013; · 4.64 Impact Factor
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ABSTRACT: Circulating CD34+ progenitor cells () gained importance in the field of regenerative medicine due to their potential to home in on injury sites and differentiate into cells of both endothelial and osteogenic lineages. In this study, we analyzed the mobilization kinetics and the numbers of CD34+, CD31+, CD45+, and CD133+ cells in twenty polytrauma patients (n = 13 male, n = 7 female, mean age 46.5±17.2 years, mean injury severity score (ISS) 35.8±12.5 points). In addition, the endothelial differentiation capacity of enriched CD34+cells was assessed by analyzing DiI-ac-LDL/lectin uptake, the expression of endothelial markers, and the morphological characteristics of these cells in Matrigel and spheroid cultures. We found that on days 1, 3, and 7 after a major trauma, the number of CD34+cells increased from 6- up to 12-fold (p<0.0001) over the number of CD34+cells from a control population of healthy, age-matched volunteers. The numbers of CD31+ cells were consistently higher on days 1 (1.4-fold, p<0.01) and 7 (1.3-fold, p<0.01), whereas the numbers of CD133+ cell did not change during the time course of investigation. Expression of endothelial marker molecules in CD34+cells was significantly induced in the polytrauma patients. In addition, we show that the CD34+ cell levels in severely injured patients were not correlated with clinical parameters, such as the ISS score, the acute physiology and chronic health evaluation II score (APACHE II), as well as the sequential organ failure assessment score (SOFA-2). Our results clearly indicate that pro-angiogenic cells are systemically mobilized after polytrauma and that their numbers are sufficient for the development of novel therapeutic models in regenerative medicine.PLoS ONE 05/2014; 9(5):e97369. · 3.53 Impact Factor
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ABSTRACT: Dipeptidylpeptidase-4 (DPP-4) is a ubiquitously expressed transmembrane protein that removes N-terminal dipeptides from various substrate hormones, chemokines, neuropeptides and growth factors. Two known substrates of DPP-4 include the incretin hormones, glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), which are secreted by enteroendocrine cells in response to postprandial hyperglycemia and account for 60-70% of postprandial insulin secretion. DPP-4 inhibitors (DPP-4i) block degradation of GLP-1 and GIP, extend their insulinotropic effect, and improve glycemia. Since 2006, several DPP-4i have become available for treatment of type 2 diabetes mellitus (T2DM). Clinical trials confirm that DPP-4i raises GLP-1 levels in plasma and improves glycemia with very low risk for hypoglycemia and other side effects. Recent studies also suggest that DPP-4i confers cardiovascular and kidney protection, beyond glycemic control, which may reduce the risk for further development of the multiple co-morbidities associated with obesity/T2DM including, hypertension and cardiovascular disease (CVD) and kidney disease. The notion that DPP-4i may improve CVD outcomes by mechanisms beyond glycemic control is due to both GLP-1-dependent and GLP-1-independent effects. The CVD protective effects by DPP-4i result from multiple factors including insulin resistance, oxidative stress, dyslipidemia, adipose tissue dysfunction, dysfunctional immunity and anti-apoptotic properties of these agents in the heart and vasculature. This review focuses on cellular and molecular mechanisms mediating the CVD protective effects of DPP-4i beyond favorable effects on glycemic control.AJP Heart and Circulatory Physiology 06/2014; · 4.01 Impact Factor