Prostaglandin E Positively Modulates Endothelial Progenitor Cell Homeostasis: An Advanced Treatment Modality for Autologous Cell Therapy

Aims: The mobilization of endothelial progenitor cells (EPC) and their functioning in postnatal neovascularization are tightly regulated. To identify new modulators of EPC homeostasis, we screened biologically active prostaglandin E compounds for their effects on EPC production, trafficking and function. Methods and Results: We found that EPC are a rich source for prostaglandin E 2 (PGE 2), stimulating their number and function in an auto- and paracrine manner. In vivo blockade of PGE 2 production by selective cyclooxygenase-2 inhibition virtually abrogated ischemia-induced EPC mobilization demonstrating its crucial role in EPC homeostasis following tissue ischemia. Conversely, ex vivo treatment of isolated EPC with the clinically approved PGE 1 analogue alprostadil enhanced EPC number and function. These effects were mediated by increased expression of the chemokine receptor CXCR4 and were dependent on nitric oxide synthase activity. Most importantly, ex vivo PGE 1 pretreatment of isolated EPC significantly enhanced their neovascularization capacity in a murine model of hind limb ischemia as assessed by laser Doppler analysis, exercise stress test and immunohistochemistry. Conclusions: The conserved role for PGE in the regulation of EPC homeostasis suggests that ex vivo modulation of the prostaglandin pathway in isolated progenitor cells may represent a novel and safe strategy to facilitate cell-based therapies. Copyright (C) 2009 S. Karger AG, Base

Microaneurysm turnover in diabetic retinopathy assessed by automated RetmarkerDR image analysis - potential role as biomarker of response to ranibizumab treatment

PURPOSE To evaluate the influence of a ranibizumab treatment on microaneurysm (MA) turnover in diabetic retinopathy. METHODS Sixty-nine eyes were included in this retrospective study. We compared a group of 33 eyes with ranibizumab treatment for diabetic macular edema to 36 eyes with nonproliferative diabetic retinopathy only. Nonmydriatic ultra-widefield scanning laser ophthalmoscopy (Optomap) images were obtained at a mean 4.76 ± 1.69 days prior to the first ranibizumab injection (baseline) and again 35.94 ± 2.44 days after the third consecutive injection in a 4-week interval. In untreated controls, images were obtained at baseline and 97.81 ± 3.16 days thereafter. Images were analyzed using the RetmarkerDR software (Critical Health SA, Coimbra, Portugal), and the turnover of MAs was documented and analyzed. Thereafter, MA turnover was correlated with central retinal thickness (CRT) as assessed by OCT. RESULTS At baseline, patients in the treatment group had 5.64 ± 0.75 MAs. One month after 3 ranibizumab injections, measured MAs decreased to 4.03 ± 0.66. In the untreated control group, the initial number of 3.36 ± 0.6 MAs remained almost unchanged over 3-4 months (2.89 ± 0.57 MAs). Dynamic analysis showed that after ranibizumab treatment 3.06 ± 0.5 new MAs appeared, while 5.09 ± 0.79 disappeared. In the control group, 2.11 ± 0.4 new MAs appeared and 2.61 ± 0.48 disappeared. MA turnover was significantly higher with ranibizumab compared to the control group (8.15 ± 1.14 vs. 4.72 ± 0.81, p < 0.001). Consistently, CRT decreased from 444 to 330 µm in the ranibizumab group, while there was no change in the control group (291 vs. 288 µm). CONCLUSION The treatment of macular edema using ranibizumab does not only reduce macular thickness, but also has an impact on the turnover of MAs in diabetic retinopathy. RetmarkerDR analysis showed that more pre-existent MAs disappeared than new MAs developed, and the absolute number of MAs also decreased

Combination of Injectable Multiple Growth Factor-Releasing Scaffolds and Cell Therapy as an Advanced Modality to Enhance Tissue Neovascularization

Objective-Vasculogenic progenitor cell therapy for ischemic diseases bears great potential but still requires further optimization for justifying its clinical application. Here, we investigated the effects of in vivo tissue engineering by combining vasculogenic progenitors with injectable scaffolds releasing controlled amounts of proangiogenic growth factors. Methods and Results-We produced biodegradable, injectable polylactic coglycolic acid-based scaffolds releasing single factors or combinations of vascular endothelial growth factor, hepatocyte growth factor, and angiopoietin-1. Dual and triple combinations of scaffold-released growth factors were superior to single release. In murine hindlimb ischemia models, scaffolds releasing dual (vascular endothelial growth factor and hepatocyte growth factor) or triple combinations improved effects of cord blood-derived vasculogenic progenitors. Increased migration, homing, and incorporation of vasculogenic progenitors into the vasculature augmented capillary density, translating into improved blood perfusion. Most importantly, scaffold-released triple combinations including the vessel stabilizer angiopoietin-1 enhanced the number of perivascular smooth muscle actin(+) vascular smooth muscle cells, indicating more efficient vessel stabilization. Conclusion-Vasculogenic progenitor cell therapy is significantly enhanced by in vivo tissue engineering providing a proangiogenic and provasculogenic growth factor-enriched microenvironment. Therefore, combined use of scaffold-released growth factors and cell therapy improves neovascularization in ischemic diseases and may translate into more pronounced clinical effectsPeer reviewe

Informative Value of Individual and Relational Data Compared Through Business-Oriented Community Detection

Abstract Despites the great interest caused by social networks in Business Science, their analysis is rarely performed in both a global and systematic way in this field. This could be explained by the fact their practical extraction is a difficult and costly task. One may ask if equivalent information could be retrieved from less expensive, individual data (i.e. describing single individuals instead of pairs). In this work, we try to address this question through group detection. We gather both types of data from a population of students, estimate groups separately using individual and relational data, and obtain sets of clusters and communities, respectively. We measure the overlap between clusters and communities, which turns out to be relatively weak. We also define a predictive model, allowing us to identify the most discriminant attributes for the communities, and to reveal the presence of a tenuous link between the relational and individual data. Our results indicate both types of data convey considerably different information in this specific context, and can therefore be considered as complementary. To emphasize the interest of communities for Business Science, we also conduct an analysis based on hobbies and purchased brands.