Biology subjects

Muinos-Lopez, E.

Publications and source records attributed to Muinos-Lopez, E..

3 recordsLinked to original sources

bioRxiv2026

Material-driven fibronectin assembly enables low-dose BMP-2 to regenerate structurally mature bone in critical-sized load-bearing defects

Bone grafts for critical-sized load-bearing defects are usually judged by how much bone forms, and rarely by whether that bone is structurally and mechanically competent. Here, degradable ceramic monetites coated with poly(ethyl acrylate) (PEA) and functionalised with fibronectin (FN) and rhBMP-2 at 10-25 g/mL, 60-150-fold below the approved clinical concentration, are assessed across length scales. MicroCT showed that only monetites functionalised with rhBMP-2 bridged the defect, with a significant increase in new bone volume in both the monetite vicinity and the whole defect volume. In contrast, platelet-rich plasma (PRP) functionalisation significantly reduced bone formation relative to FN, showing that the identity of the adhesion cue, and not merely its presence, determines the outcome. Monetite degradation and increased interconnected porosity favoured bone ingrowth and produced a continuous interface between monetite and new bone. The multiscale analyses of quantitative polarised light microscopy, SAXS and nanoindentation show that PEA-coated monetites functionalised with FN and 25 g/mL rhBMP-2 promoted structurally and mechanically more mature bone, with a hierarchical organisation and local mechanical properties approaching those of native cortical tissue. In the bridged region this group recapitulated the preferential collagen fibre orientation of native cortical bone and reached an elastic modulus and hardness that were not statistically distinguishable from it, although mineral particles throughout the regenerated tissue remained thicker and less aligned than in cortical bone. Synchrotron microCT in an ovine model extended these findings to a clinically relevant scale, supporting the translational potential of the system. Taken together, these findings position PEA-coated monetites functionalised with FN and low-dose rhBMP-2 as a strategy for the structural and functional regeneration of large bone defects.

bioengineering↗

bioRxiv2024

Unravelling the molecular activation of the reparative cardiac fibroblasts after myocardial infarction

Activated cardiac fibroblasts (Postn+ CFs) are responsible for the healing of the heart tissue after a myocardial infarction (MI). However, so far little is known about the moment that CFs are activated, and the genes involved in this process. This is especially relevant in the context of CF heterogeneity and their role in the response to the damage. In this context, we have described a subpopulation of activated CFs responsible for the healing scar and for preventing the rupture of the ventricle after the damage: the Reparative Cardiac Fibroblasts (RCFs). Our new data indicate that RCFs directly derived from activated CFs, and this transcriptional shift happens in a close window after damage. Interestingly, our results exhibited two different molecular dynamics that would give rise to this activation and, consequently, the appearance of definitive RCFs. Using bulk RNA-Seq, RNAScope and Spatial Transcriptomics, we anatomically localized some of the genes related to both dynamics in the infarcted heart and highlight the potential role of Aspn as a new marker of this transcriptional transition in mice, pigs and patients.

bioinformatics↗

bioRxiv2024

Spatial Transcriptomics Reveals a Myeloma Cell Architecture with Dysfunctional T-Cell Distribution, Neutrophil Traps, and Inflammatory Signaling

The bone marrow (BM) is a complex tissue where spatial relationships influence cell behavior, signaling, and function. Consequently, understanding the whole dynamics of cellular interactions requires complementary spatial techniques that preserve and map the architecture of cell populations in situ. We successfully conducted spatial transcriptional profiling using Visium Spatial Gene Expression in formalin-fixed paraffin-embedded (FFPE) BM samples obtained from healthy and Multiple Myeloma (MM) mouse models and patients, addressing the technical challenges of applying spatial technology to long bone samples. A custom data-analysis framework that combines spatial with single-cell transcriptomic profiles identified both the BM cellular composition and the existing cell relations. This allowed us to visualize the spatial distribution of transcriptionally heterogeneous MM plasma cells (MM-PC). We spatially delineated transcriptional programs associated with MM, including NETosis and IL-17-driven inflammatory signaling, which were inversely correlated to malignant PC-enriched regions. Furthermore, a gradient of MM-PC density spatially correlated with a shift from effector-to-exhausted T cell phenotypes. The translational relevance of our findings was confirmed using FFPE BM biopsies from MM patients with varying levels of malignant PC infiltration. In summary, we provide the first spatial transcriptomics analysis applied to a mouse and human mineralized bone tissue and illustrate the BM cellular architecture of MM, revealing deregulated mechanisms underlying MM intercellular communication.

cancer biology↗