Alginate Scaffolds for Mesenchymal Stem Cell Cardiac Therapy: Influence of Alginate Composition

Despite the success of alginate scaffolds and mesenchymal stem cells (MSCs) therapy in cardiac failure treatment, the impact of the physicochemical environment provided by alginate matrices on cell behavior has never been investigated. The purpose of this work was double: to determine the alginate composition influence on (1) encapsulated rat MSC viability, paracrine activity, and phenotype in vitro and (2) cardiac implantability and in vivo biocompatibility of patch shape scaffolds. Two alginates, differing in composition and thus presenting different mechanical properties when hydrogels, were characterized. In both cases, encapsulated MSC viability was maintained at around 75%, and their secretion characteristics were retained 28 days postencapsulation. In vivo study revealed a high cardiac compatibility of the tested alginates: cardiac parameters were maintained, and rats did not present any sign of infection. Moreover, explanted hydrogels appeared surrounded by a vascularized tissue. However, scaffold implantability was highly dependent on alginate composition. G-type alginate patches, presenting higher elastic and Young moduli than M-type alginate patches, showed a better implantation easiness and were the only ones that maintained their shape and morphology in vivo. As a consequence of alginate chemical composition and resulting hydrogel structuration, G-type alginate hydrogels appear to be more adapted for cardiac implantation

The effect of rearing temperature in larval development of pejerrey, Odontesthes bonariensis- Morphological indicators of development

It is well known that in pejerrey water temperature not only affects growth rates but also directs the sexual differentiation process. This fact rise the question of how different the development of pejerrey larvae of the same age is when reared at different temperatures. A description of developmental stages for the embryonic and larval periods of the pejerrey, Odontesthes bonariensis, and the influence of rearing temperature on larval development are presented. Then, larval development was studied at three rearing temperatures, and changes in general morphology, fin morphology, and caudal fin structure have been taken into consideration within the thermal range involved in the temperature sex determination of this species. Fin fold reabsorption, caudal fin formation, and body shape were selected to follow the events leading to the acquisition of the juvenile morphology. The juvenile phenotype was defined when the fin fold was reabsorpted and the caudal fin acquired its definitive homocercal structure. The moment at which the juvenile phenotype was achieved, was evaluated in relation to larval age, size and, shape. The size resulted as the best indicator of development in pejerrey.A temperatura da água não afeta apenas as taxas de crescimento no peixe-rei, mas também direciona o processo de diferenciação sexual. Este fato levanta o questionamento de quão diferente é o desenvolvimento de larvas do peixe-rei da mesma idade quando criadas em temperaturas diferentes. Este trabalho teve como objetivo apresentar uma descrição do de desenvolvimento de embriões e larvas do peixe-rei, Odontesthes bonariensis, e a influência da temperatura de criação no desenvolvimento das larvas. Neste trabalho, o desenvolvimento das larvas foi estudado em três temperaturas diferentes de cultivo. Foram consideradas as alterações ocorridas na morfologia geral, assim como na morfologia e na estrutura da nadadeira caudal dentro da variação termal da temperatura de determinação sexual desta espécie. A taxa de reabsorção da membrana embrionária, a formação da cauda e o formato do corpo foram selecionados para acompanhar os eventos que levam à aquisição da morfologia juvenil. O fenótipo juvenil foi definido quando a nadadeira caudal foi reabsorvida e a cauda adquiriu a estrutura homocerca. O momento no qual o fenótipo juvenil foi atingido, foi avaliado quanto à idade, tamanho e formato da larva, sendo que o tamanho resultou no melhor indicador do desenvolvimento do peixe-rei.Fil: Chalde, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); ArgentinaFil: Fernandez, Daniel Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Cussac, Victor Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Patagonia Norte. Instituto de Investigación En Biodiversidad y Medioambiente; ArgentinaFil: Somoza, Gustavo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentin

Characterization of Monoamine Oxidases in Mesenchymal Stem Cells: Role in Hydrogen Peroxide Generation and Serotonin-Dependent Apoptosis

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Elaboration and evaluation of alginate foam scaffolds for soft tissue engineering

Controlling microarchitecture in polymer scaffolds is a priority in material design for soft tissue applications. This paper reports for the first time the elaboration of alginate foam-based scaffolds for mesenchymal stem cell (MSC) delivery and a comparative study of various surfactants on the final device performance. The use of surfactants permitted to obtain highly interconnected porous scaffolds with tunable pore size on surface and in cross-section. Their mechanical properties in compression appeared to be adapted to soft tissue engineering. Scaffold structures could sustain MSC proliferation over 14 days. Paracrine activity of scaffold-seeded MSCs varied with the scaffold structure and growth factors release was globally improved in comparison with control alginate scaffolds. Our results provide evidence that exploiting different surfactant types for alginate foam preparation could be an original method to obtain biocompatible scaffolds with tunable architecture for soft tissue engineering

Fishes of southern South America: a story driven by temperature

The latitudinal extension of southern South America imposes a thermal gradient that affects the structure of marine and freshwater fish assemblages and the biology of the species through direct exposure to the temperature gradients or by means of a web of historical and ecological relationships. We have reviewed biological and ecological data of marine and freshwater fishes from the southern Neotropics, including Patagonia, and report several examples of dependence on temperature, from glacial times to today’s climate change. We were able to identify historic and present effects on the diversity of fish assemblages, isolation, southern limits for the distribution of species, and morphological variation among populations. There is a wide range of characteristics that exemplify an adaptation to low temperatures, including biochemical peculiarities, physiological adjustments, and alternative life history patterns, and these appear in both freshwater and marine, and native and exotic fishes. The consequences of stable temperature regimes in both the ocean and thermal streams deserve special mention as these shape specialists under conditions of low selective pressure. At present, habitat use and interactions among species are being subject to changes as consequences of water temperature, and some of these are already evident in the northern and southern hemispheres.Facultad de Ciencias Naturales y Muse

Evaluation of alginate microspheres for mesenchymal stem cell engraftment on solid organ

Mesenchymal stem cells (MSCs) may be used as a cell source for cell therapy of solid organs due to their differentiation potential and paracrine effect. Nevertheless, optimization of MSC-based therapy needs to develop alternative strategies to improve cell administration and efficiency. One option is the use of alginate microencapsulation, which presents an excellent biocompatibility and an in vivo stability. As MSCs are hypoimmunogenic, it was conceivable to produce microparticles with [alginate-poly-L-lysine-alginate (APA) microcapsules] or without (alginate microspheres) a surrounding protective membrane. Therefore, the aim of this study was to determine the most suitable microparticles to encapsulate MSCs for engraftment on solid organ. First, we compared the two types of microparticles with 4 × 106 MSCs/ml of alginate. Results showed that each microparticle has distinct morphology and mechanical resistance but both remained stable over time. However, as MSCs exhibited a better viability in microspheres than in microcapsules, the study was pursued with microspheres. We demonstrated that viable MSCs were still able to produce the paracrine factor bFGF and did not present any chondrogenic or osteogenic differentiation, processes sometimes reported with the use of polymers. We then proved that microspheres could be implanted under the renal capsule without degradation with time or inducing impairment of renal function. In conclusion, these microspheres behave as an implantable scaffold whose biological and functional properties could be adapted to fit with clinical applications

058 The ongoing MESAMI translational research program

PurposeDespite the improvement of pharmacological and surgical therapies, the mortality related to ischemic heart failure remains high. During the last years, bone marrow-mesenchymal stem cell (BM-MSC) therapy has been proposed as a novel approach for the prevention and therapy of heart failure. Intramyocardial injection allows concentration of grafted cells within the injured zone. However, a major problem of with intraparenchymal route of administration is the early death of most of grafted cells. The goal of the MESAMI program is to evaluate the effect of intramyocardial administration of BM-MSC preconditioned or not with the pineal hormone melatonin in ischemic cardiomyopathy.Methods and ResultsOur preclinical investigations have designed a preconditioning strategy of BM-MSCs with the melatonin that significantly increases survival and efficacy of grafted cells in animal models of myocardial ischemia. Melatonin treatment significantly ameliorates the beneficial effects of BM-MSC on the recovery of cardiac function. In the mean time, we started a phase I clinical trial in patients with severe ischemic cardiomyopathy and no option of revascularization, using the NOGA XP system to guide injections into the myocardium. Based on our basic research results, we are developing a multicenter phase II trial on the effects of intramyocardial administration of melatonin-preconditioned BM-MSC in patients with chronic ischemic cardiomyopathy.ConclusionThe ongoing MESAMI program is representative of a translational research program in France

Evaluation of polyelectrolyte complex-based scaffolds for mesenchymal stem cell therapy in cardiac ischemia treatment

Three-dimensional (3D) scaffolds hold great potential for stem cell-based therapies. Indeed, recent results have shown that biomimetic scaffolds may enhance cell survival and promote an increase in the concentration of therapeutic cells at the injury site. The aim of this work was to engineer an original polymeric scaffold based on the respective beneficial effects of alginate and chitosan. Formulations were made from various alginate/chitosan ratios to form opposite-charge polyelectrolyte complexes (PECs). After freeze-drying, the resultant matrices presented a highly interconnected porous microstructure and mechanical properties suitable for cell culture. In vitro evaluation demonstrated their compatibility with mesenchymal stell cell (MSC) proliferation and their ability to maintain paracrine activity. Finally, the in vivo performance of seeded 3D PEC scaffolds with a polymeric ratio of 40/60 was evaluated after an acute myocardial infarction provoked in a rat model. Evaluation of cardiac function showed a significant increase in the ejection fraction, improved neovascularization, attenuated fibrosis as well as less left ventricular dilatation as compared to an animal control group. These results provide evidence that 3D PEC scaffolds prepared from alginate and chitosan offer an efficient environment for 3D culturing of MSCs and represent an innovative solution for tissue engineering

Alginate-chitosan PEC scaffolds: A useful tool for soft tissues cell therapy

In this study we evaluate macroporous scaffolds made of alginate-chitosan polyelectrolyte complexes (PEC) as tools to optimize the results of soft tissues cell therapy. Cell therapy using mesenchymal stem cells (MSC) has become attractive for tissue repair and regeneration in a number of acute and chronic injuries. Unfortunately their low retention and/or survival after injection limit their beneficial effects. A biomaterial-assisted implantation, providing cells a three-dimensional (3D) microenvironment is a promising strategy. To this purpose, we designed a family of PEC scaffolds, and studied if they could meet the requirement of such application. Xray tomography showed that all PEC scaffolds present an interconnected macroporosity, and both rheology and tensile measurements reveal optimized mechanical properties (higher storage moduli and Young moduli) compared to alginate reference scaffolds. In vitro assays demonstrated their ability to allow MSC retention (higher than 90%), long-term viability and FGF2 secretion. Then, we used a skeletal muscle implantation model to assess the biological response to scaffolds graft, and showed that they support in vivo vascular formation within the implant-derived tissue. The combination of alginate/chitosan PEC scaffolds architecture and angiogenic potential make them appear as interesting tools to optimize MSC therapy results in soft tissues

Evaluation of polyelectrolyte complex-based scaffolds for mesenchymal stem cell therapy in cardiac ischemia treatment

b s t r a c t Three-dimensional (3D) scaffolds hold great potential for stem cell-based therapies. Indeed, recent results have shown that biomimetic scaffolds may enhance cell survival and promote an increase in the concentration of therapeutic cells at the injury site. The aim of this work was to engineer an original polymeric scaffold based on the respective beneficial effects of alginate and chitosan. Formulations were made from various alginate/chitosan ratios to form opposite-charge polyelectrolyte complexes (PECs). After freeze-drying, the resultant matrices presented a highly interconnected porous microstructure and mechanical properties suitable for cell culture. In vitro evaluation demonstrated their compatibility with mesenchymal stell cell (MSC) proliferation and their ability to maintain paracrine activity. Finally, the in vivo performance of seeded 3D PEC scaffolds with a polymeric ratio of 40/60 was evaluated after an acute myocardial infarction provoked in a rat model. Evaluation of cardiac function showed a significant increase in the ejection fraction, improved neovascularization, attenuated fibrosis as well as less left ventricular dilatation as compared to an animal control group. These results provide evidence that 3D PEC scaffolds prepared from alginate and chitosan offer an efficient environment for 3D culturing of MSCs and represent an innovative solution for tissue engineering