Activation of ß-catenin in mesenchymal progenitors leads to muscle mass loss.

Loss of muscle mass is a common manifestation of chronic disease. We find the canonical Wnt pathway to be activated in mesenchymal progenitors (MPs) from cancer-induced cachectic mouse muscle. Next, we induce ß-catenin transcriptional activity in murine MPs. As a result, we observe expansion of MPs in the absence of tissue damage, as well as rapid loss of muscle mass. Because MPs are present throughout the organism, we use spatially restricted CRE activation and show that the induction of tissue-resident MP activation is sufficient to induce muscle atrophy. We further identify increased expression of stromal NOGGIN and ACTIVIN-A as key drivers of atrophic processes in myofibers, and we verify their expression by MPs in cachectic muscle. Finally, we show that blocking ACTIVIN-A rescues the mass loss phenotype triggered by ß-catenin activation in MPs, confirming its key functional role and strengthening the rationale for targeting this pathway in chronic disease.

Collagen-Based Microcapsules As Therapeutic Materials for Stem Cell Therapies in Infarcted Myocardium.

As cell therapies emerged, it was quickly realized that pro-regenerative cells directly injected into injured tissue struggled within the inflammatory microenvironment. By using microencapsulation, i.e., encapsulating cells within polymeric biomaterials, they are henceforth protected from the harmful extracellular cues, while still being able to receive oxygen and nutrients and release secreted factors. Previous work showed that stem cells encapsulated within a biologically inert material (agarose) were able to significantly improve the function of the infarcted mouse heart. With the aim of using more bioresponsive microcapsules, we sought to develop an enzymatically degradable, type I collagen-based microcapsule for the intramyocardial delivery of bone marrow-derived mesenchymal stromal cells in a murine model of myocardial infarction.

Nanoparticle Concentration vs Surface Area in the Interaction of Thiol-Containing Molecules: Toward a Rational Nanoarchitectural Design of Hybrid Materials.

The effect of accounting for the total surface in the association of thiol-containing molecules to nanosilver was assessed using isothermal titration calorimetry, along with a new open access algorithm that calculates the total surface area for samples of different polydispersity. Further, we used advanced molecular dynamic calculations to explore the underlying mechanisms for the interaction of the studied molecules in the presence of a nanosilver surface in the form of flat surfaces or as three-dimensional pseudospherical nanostructures. Our data indicate that not only is the total surface area available for binding but also the supramolecular arrangements of the molecules in the near proximity of the nanosilver surface strongly affects the affinity of thiol-containing molecules to nanosilver surfaces.

Effect of nanosilver surfaces on peptide reactivity towards reactive oxygen species.

The interaction of a terminal tryptophan residue within collagen mimetic peptides when tethered to nanometric silver surfaces was studied using a combination of steady state spectroscopy, ultrafast spectroscopy, and molecular dynamics experiments. Our findings indicate that the effective interaction between the tryptophan and the metal surface occurs in short-time scales (ps) and it is responsible for improving the colloidal stability of the nanoparticles exposed to free radicals. The extent and efficiency of the interaction depends on factors beyond the peptide length that include conformation and distance from the terminal tryptophan to the metal surface.