Synthetic matrix enhances transplanted satellite cell engraftment in dystrophic and aged skeletal muscle with comorbid trauma

Muscle satellite cells (MuSCs) play a central role in muscle regeneration, but their quantity and function decline with comorbidity of trauma, aging, and muscle diseases. Although transplantation of MuSCs in traumatically injured muscle in the comorbid context of aging or pathology is a strategy to boost muscle regeneration, an effective cell delivery strategy in these contexts has not been developed. We engineered a synthetic hydrogel-based matrix with optimal mechanical, cell-adhesive, and protease-degradable properties that promotes MuSC survival, proliferation, and differentiation. Furthermore, we establish a biomaterial-mediated cell delivery strategy for treating muscle trauma, where intramuscular injections may not be applicable. Delivery of MuSCs in the engineered matrix significantly improved in vivo cell survival, proliferation, and engraftment in nonirradiated and immunocompetent muscles of aged and dystrophic mice compared to collagen gels and cell-only controls. This platform may be suitable for treating craniofacial and limb muscle trauma, as well as postoperative wounds of elderly and dystrophic patients.Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH under award numbers R21AR072287 (to Y.C.J.) and R01AR062368 (to A.J.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was also funded by the Parker H. Petit Institute for Bioengineering and Bioscience Seed Grant Program (to A.J.G. and Y.C.J.)

Synthetic matrix enhances transplanted satellite cell engraftment in dystrophic and aged skeletal muscle with comorbid trauma

Muscle satellite cells (MuSCs) play a central role in muscle regeneration, but their quantity and function decline with comorbidity of trauma, aging, and muscle diseases. Although transplantation of MuSCs in traumatically injured muscle in the comorbid context of aging or pathology is a strategy to boost muscle regeneration, an effective cell delivery strategy in these contexts has not been developed. We engineered a synthetic hydrogel-based matrix with optimal mechanical, cell-adhesive, and protease-degradable properties that promotes MuSC survival, proliferation, and differentiation. Furthermore, we establish a biomaterial-mediated cell delivery strategy for treating muscle trauma, where intramuscular injections may not be applicable. Delivery of MuSCs in the engineered matrix significantly improved in vivo cell survival, proliferation, and engraftment in nonirradiated and immunocompetent muscles of aged and dystrophic mice compared to collagen gels and cell-only controls. This platform may be suitable for treating craniofacial and limb muscle trauma, as well as postoperative wounds of elderly and dystrophic patients.Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH under award numbers R21AR072287 (to Y.C.J.) and R01AR062368 (to A.J.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was also funded by the Parker H. Petit Institute for Bioengineering and Bioscience Seed Grant Program (to A.J.G. and Y.C.J.)

Adenosine A(2A) receptor blockade reverts hippocampal stress-induced deficits and restores corticosterone circadian oscillation

Maternal separation (MS) is an early life stress model that induces permanent changes in the central nervous system, impairing hippocampal long-term potentiation (LTP) and spatial working memory. There are compelling evidences for a role of hippocampal adenosine A(2A) receptors in stress-induced modifications related to cognition, thus opening a potential window for therapeutic intervention. Here, we submitted rats to MS and evaluated the long-lasting molecular, electrophysiological and behavioral impairments in adulthood. We then assessed the therapeutic potential of KW6002, a blocker of A(2A) receptors, in stress-impaired animals. We report that the blockade of A(2A) receptors was efficient in reverting the behavior, electrophysiological and morphological impairments induced by MS. In addition, this effect is associated with restoration of the hypothalamic-pituitary-adrenal axis (HPA-axis) activity, as both the plasma corticosterone levels and hippocampal glucocorticoid receptor expression pattern returned to physiological-like status after the treatment. These results reveal the involvement of A(2A) receptors in the stress-associated impairments and directly in the stress response system by showing that the dysfunction of the HPA-axis as well as the long-lasting synaptic and behavioral effects of MS can be reverted by targeting adenosine A(2A) receptors. These findings provide a novel evidence for the use of adenosine A(2A) receptor antagonists as potential therapy against psychopathologiesWe acknowledge Alexandre de Mendonca, David Blum and Rodrigo Cunha for helpful discussions. VLB is thankful to Joao Baiao and Carla Batalha for technical assistance. VLB has been awarded a PhD fellowship from Fundacao para a Ciencia e Tecnologia (BD/63041/2009). LVL is funded by Fundacao para a Ciencia e Tecnologia (PTDC/SAU-NEU/099853/2008) and by EU programme Egide-Pessoa. YB and CEM were funded by the Ministry for Education and Research (BMBF, Grant number 01EW0911) in the frame of ERA-NET NEURON

"Fandango": long term adaptation of exotic germplasm to a Portuguese on-farm-conservation and breeding project

Climatic change emphasize the importance of biodiversity maintenance, Suggesting that germplasm adapted to organic, low input, or conventional conditions is needed to face future demands. This Study presents: I - The two steps genesis of the synthetic maize population 'Fandango', A) 'NUTICA' creation: in 1975, Miguel Mota and Silas Pego, initiated a new type of polycross method involving 77 yellow elite inbred lines (dent and flint; 20% Portuguese and 80% North American germplasm) from the NUMI programme (NUcleo de melhoramento de Milho, Braga, Portugal). These inbreds were intermated in natural isolation and progenies submitted to intensive selection for both parents during continued cycles; B) From 'NUTICA' to 'Fandango': Tandango' was composed of all the crosses that resulted from a North Carolina Design I matting design (1 male crossed with 5 females) applied to 'NUTICA'. II - The diversity evolution of 'Fandango' under a Participatory Breeding project at the Portuguese Sousa Valley region (VASO) initiated in 1985 by Pego, with CIMMYT support. Morphological, fasciation expression, and yield trials were conducted in Portugal (3 locations, 3 years) and in the USA (4 locations, I year) using seeds obtained from five to seven cycles of mass selection (MS). The selection across cycles wits clone by the breeder (until cycle 5) and farmer (before cycle II in present). ANOVA and regression analysis on the rate of direct response to selection were performed when the assumption of normality was positively confirmed. Otherwise the non parametric Multivariate Adaptive Regression Splines (MARS) was performed. Response to mass selection in lowa showed significant decrease in yield, while in Portugal a significant increase for time of silking, plant and ear height, ear diameters 2, 37 4, kernel number, cot) diameters, and rachis was observed. At this location also a significant decrease was observed for thousand kernel weight and ear length. These results showed that mass selection were not effective for significant yield increase, except when considered Lousada with breeder selection (3.09% of gain per cycle per year). Some non-para metric methods (MARS, decision trees and random forests) were used to get insights on the causes that explain yield in Fandango. Kernel weight and ear weight were the most important traits, although row numbers, number of kernels per row, ear length, and ear diameter were also of some importance influencing 'Fandango' yield

Stress-induced anhedonia is associated with hypertrophy of medium spiny neurons of the nucleus accumbens

There is accumulating evidence that the nucleus accumbens (NAc) has an important role in the pathophysiology of depression. As the NAc is a key component in the neural circuitry of reward, it has been hypothesized that anhedonia, a core symptom of depression, might be related to dysfunction of this brain region. Neuronal morphology and expression of plasticity-related molecules were examined in the NAc of rats displaying anhedonic behavior (measured in the sucrose-consumption test) in response to chronic mild stress. To demonstrate the relevance of our measurements to depression, we tested whether the observed changes were sensitive to reversal with antidepressants (imipramine and fluoxetine). Data show that animals displaying anhedonic behavior display an hypertrophy of medium spiny neurons in the NAc and, in parallel, have increased expression of the genes encoding for brain-derived neurotrophic factor, neural cell adhesion molecule and synaptic protein synapsin 1. Importantly, the reversal of stress-induced anhedonia by antidepressants is linked to a restoration of gene-expression patterns and dendritic morphology in the NAc. Using an animal model of depression, we show that stress induces anhedonic behavior that is associated with specific changes in the neuronal morphology and in the gene-expression profile of the NAc that are effectively reversed after treatment with antidepressants.The present work was funded by the Portuguese Foundation for Technology (FCT), project PTDC/SAU-NEU/105180/2008. FM and PL are recipients of postdoctoral fellowships and MM is recipient of a doctoral fellowship, all from FCT, Portugal

Twenty-Five Years of Convoluted Health Reforms in Mexico

Núria Homedes and Antonio Ugalde discuss 25 years of reform to the Mexican health care system and argue that although costs and accessibility have increased, health inequities, efficiency, productivity, and quality of care have not improved