Díaz-Herráez, P. (Paula)
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- Biodegradation and heart retention of polymeric microparticles in a rat model of myocardial ischemia(Elsevier, 2013) Blanco-Prieto, M.J. (María José); Díaz-Herráez, P. (Paula); Tamayo, E. (Esther); Garbayo, E; Prosper-Cardoso, F. (Felipe); Formiga, F.R. (Fabio R.); Simon-Yarza, T. (Teresa); Abizanda-Sarasa, G. (Gloria)Poly-lactide-co-glycolide (PLGA) microparticles emerged as one of the most promising strategies to achieve site-specific drug delivery. Although these microparticles have been demonstrated to be effective in several wound healing models, their potential in cardiac regeneration has not yet been fully assessed. The present work sought to explore PLGA microparticles as cardiac drug delivery systems. PLGA microparticles were prepared by Total Recirculation One-Machine System (TROMS) after the formation of a multiple emulsion. Microparticles of different size were prepared and characterized to select the most suitable size for intramyocardial administration. Next, the potential of PLGA microparticles for administration in the heart was assessed in a MI rat model. Particle biodegradation over time and myocardial tissue reaction were studied by routine staining and confocal microscopy. Results showed that microparticles with a diameter of 5 μm were the most compatible with intramyocardial administration in terms of injectability through a 29-gauge needle and tissue response. Particles were present in the heart tissue for up to three months post-implantation and no particle migration towards other solid organs was observed, demonstrating good myocardial retention. CD68 immunolabeling revealed 31%, 47% and below 4% microparticle uptake by macrophages one week, one month and three months after injection, respectively (P<0.001). Taken together, these findings support the feasibility of the developed PLGA microparticles as vehicles for delivering growth factors in the infarcted myocardium.
- Novel tissue engineering strategies based on the combination of the polymeric devices and adult stem cells for cardiac repair(2020-01-30) Díaz-Herráez, P. (Paula); Blanco-Prieto, M.J. (María José); Garbayo, E; Garbayo, E. (Elisa)Cardiovascular diseases (CVD) are the leading cause of death worldwide. Among them, myocardial infarction (MI) is the main CVDs, causing 7.4 million deaths each year. The current therapies for MI are palliative rather than regenerative. Since that, the tissue engineering (TE) strategy has grown investigators attention. With the aim of improving heart repair after MI, we have developed two TE strategies. The first strategy was the use of poly(lactic co-glycolic acid) (PLGA) microparticles (MPs) containing neuregulin (NRG), as support for attaching adipose-derived stem cells (ADSC): ADSC-NRG-MP. The second strategy was the combination of two different polymeric devices, MPs and hydrogels. The MPs loaded with NRG were embedded together with the ADSCs in hydrogels composed of different ratios of dextran (Dex) and hyaluronic acid (HA). Our hypothesis was that the developed systems would increase cell survival and would activate different pathways to favor heart regeneration. The ADSC-NRG-MP induced a more pronounced regeneration of the infarcted heart in a rat MI model (reduction in infarct size, higher left ventricle thickness and vasculogenesis). Also the employment of MPs as support for the ADSC, favored a long-term survival of the cells once in the tissue, being detectable three months after their administration. Moreover, among the hydrogels developed, the 50:50 Dex:HA hydrogel embedding 1 mg of NRG-MP and 500,000 ADSC showed to present the best characteristics (adequate stiffness for heart administration, prolonged gelation time to allow its injectability and degradation rate to allow cell survival). To conclude, the two strategies developed have shown to be promising candidates for heart repair after a MI.
- Adipose-derived stem cells combined with Neuregulin-1 delivery systems for heart tissue engineering(Elsevier, 2013) Blanco-Prieto, M.J. (María José); Díaz-Herráez, P. (Paula); Garbayo, E; Prosper-Cardoso, F. (Felipe); Formiga, F.R. (Fabio R.); Simon-Yarza, T. (Teresa)Myocardial infarction (MI) is the leading cause of death worldwide and extensive research has therefore been performed to find a cure. Neuregulin-1 (NRG) is a growth factor involved in cardiac repair after MI. We previously described how biocompatible and biodegradable microparticles, which are able to release NRG in a sustained manner, represent a valuable approach to avoid problems related to the short half-life after systemic administration of proteins. The effectiveness of this strategy could be improved by combining NRG with several cytokines involved in cardiac regeneration. The present study investigates the potential feasibility of using NRG-releasing particle scaffold combined with adipose derived stem cells (ADSC) as a multiple growth factor delivery-based tissue engineering strategy for implantation in the infarcted myocardium. NRG-releasing particle scaffolds with a suitable size for intramyocardial implantation were prepared by TROMS. Next, ADSC were adhered to particle scaffolds and their potential for heart administration was assessed in a MI rat model. NRG was successfully encapsulated reaching encapsulation efficiencies of 92.58 ± 3.84 %. NRG maintained its biological activity after the microencapsulation process. ADSC cells adhered efficiently to particle scaffolds within a few hours. The ADSC-cytokine delivery system developed proved to be compatible with intramyocardial administration in terms of injectability through a 23-gauge needle and tissue response. Interestingly, ADSC-scaffolds were present in the peri-infarted tissue two weeks after implantation. This proof of concept study provides important evidence required for future effectiveness studies and for the translation of this approach.
- Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration(Elsevier, 2014) Blanco-Prieto, M.J. (María José); Díaz-Herráez, P. (Paula); Gavira, J.J. (Juan José); Tamayo, E. (Esther); Albiasu, E. (Edurne); Garbayo, E; Prosper-Cardoso, F. (Felipe); Formiga, F.R. (Fabio R.); Pelacho, B. (Beatriz); Simon-Yarza, T. (Teresa); Abizanda-Sarasa, G. (Gloria); Imbuluzqueta, I. (Izaskun)Acidic fibroblast growth factor (FGF1) and neuregulin-1 (NRG1) are growth factors involved in cardiac development and regeneration. Microparticles (MPs) mediate cytokine sustained release, and can be utilized to overcome issues related to the limited therapeutic protein stability during systemic administration. We sought to examine whether the administration of microparticles (MPs) containing FGF1 and NRG1 could promote cardiac regeneration in a myocardial infarction (MI) rat model. We investigated the possible underlying mechanisms contributing to the beneficial effects of this therapy, especially those linked to endogenous regeneration. FGF1- and NRG1-loaded MPs were prepared using a multiple emulsion solvent evaporation technique. Seventy-three female Sprague-Dawley rats underwent permanent left anterior descending coronary artery occlusion, and MPs were intramyocardially injected in the peri-infarcted zone four days later. Cardiac function, heart tissue remodeling, revascularization, apoptosis, cardiomyocyte proliferation, and stem cell homing were evaluated one week and three months after treatment. MPs were shown to efficiently encapsulate FGF1 and NRG1, releasing the bioactive proteins in a sustained manner. Three months after treatment, a statistically significant improvement in cardiac function was detected in rats treated with growth factor-loaded MPs (FGF1, NRG1, or FGF1/NRG1). The therapy led to inhibition of cardiac remodeling with smaller infarct size, a lower fibrosis degree and induction of tissue revascularization. Cardiomyocyte proliferation and progenitor cell recruitment was detected. Our data support the therapeutic benefit of NRG1 and FGF1 when combined with protein delivery systems for cardiac regeneration. This approach could be scaled up for use in pre-clinical and clinical studies.
- Heart regeneration after miocardial infarction using synthetic biomaterials(Elsevier, 2015) Pascual-Gil, S. (Simón); Blanco-Prieto, M.J. (María José); Díaz-Herráez, P. (Paula); Garbayo, E; Prosper-Cardoso, F. (Felipe)Myocardial infarction causes almost 7.3 million deaths each year worldwide. However, current treatments are more palliative than curative. Presently, cell and protein therapies are considered the most promising alternative treatments. Clinical trials performed until now have demonstrated that these therapies are limited by protein short half‐life and by low transplanted cell survival rate, prompting the development of novel cell and protein delivery systems able to overcome such limitations. In this review we discuss the advances made in the last 10 years in the emerging field of cardiac repair using biomaterial‐based delivery systems with focus on the progress made on preclinical in vivo studies. Then, we focus in cardiac tissue engineering approaches, and how the incorporation of both cells and proteins together into biomaterials has opened new horizons in the myocardial infarction treatment. Finally, the ongoing challenges and the perspectives for future work in cardiac tissue engineering will also be discussed.
- Prevalence of paid sex and associated factors among women and men attending HIV voluntary counseling and testing in Kinshasa, Democratic Republic of the Congo: a prospective cohort(Springer, 2024) Carlos-Chillerón, S. (Silvia); Burgueño, E. (Eduardo); Makonda, B. (Benit); Díaz-Herráez, P. (Paula); Irala, J. (Jokin) de; Reina, G. (Gabriel); Lopez-del-Burgo, C. (Cristina); Beltramo, C. (Carlos)Paid sex is associated with HIV and other sexually transmitted infections, which are highly prevalent in Sub-Saharan Africa (SSA). However, few data exist on this sexual practice among the general population in SSA, including the Democratic Republic of the Congo, where data on paid sex mainly comes from sex workers. In the DRC, most HIV Voluntary Counseling and Testing (VCT) centers do not discuss paid sex as a risk factor. Thus, we aimed to analyze the prevalence of paid sex, its associated factors and association with HIV among women and men attending HIV VCT at a reference hospital in Kinshasa. From 2016 to 2018, the Observational Kinshasa AIDS Initiative cohort analyzed the impact of HIV VCT on changes in HIV knowledge, attitudes, and sexual behaviors at follow-up. Participants aged 15–69 years were HIV tested and interviewed at baseline and at 6- and 12-month follow-ups. At baseline, participants were asked about their history of “ever” having had exchanged sex for money. At both follow-ups, the frequency of this practice was referred to as “the previous 6 months.” Descriptive, bivariate, and multivariate logistic regression analyses were carried out to evaluate the prevalence of paid sex, its associated factors, and the association between paid sex and HIV. Statistical analyses were performed with Stata 15.1. Among 797 participants at baseline, 10% of those sexually experienced reported having ever had paid sex (18% men and 4% women, p<0.001). At 6 and 12-month follow-ups, 5% and 2%, respectively. Paid sex was signifcantly and independently associated with being male (aOR=2.7; 95% CI=1.4–5.2), working or studying (aOR=2.8; 95% CI=1.5–5.0), daily newspaper reading (aOR=4.4; 95% CI=1.7–11.2); daily/weekly alcohol consumption (aOR=3.3; 95% CI=1.8–6.1), frst sexual intercourse before age 15 years (aOR=2.3; 95% CI=1.1–5.0), multiple sexual partners (aOR=4.1; 95% CI=2.2–7.7), and extragenital sexual practices (aOR=2.4; 95% CI=1.3–4.4). A high religiosity (daily/weekly church attendance and praying) was inversely associated with paid sex (aOR=0.1; 95% CI=0.0–0.4). The high prevalence of paid sex among people attending HIV VCT in Kinshasa, associated with other sexual and consumption risk behaviors, highlights the need to include paid sex among the risk factors mentioned in HIV prevention counseling.