The heart of the tissue: Modeling basement membrane assembly and dynamics

Synopsis

Research in the Braid lab focuses on human mesenchymal stromal cells (MSCs), an enigmatic population of progenitor cells that function as signaling hubs to coordinate immune and progenitor cell behaviour. MSCs reside in basement membrane niches, including the perivascular region surrounding blood vessels and in the organizing compartment of many stem cell niches. Considerable research has shown that MSCs have useful clinical benefits including reducing inflammation and promoting regeneration, but the endogenous function of MSCs remains unclear. Our lab recently discovered that activation of MSCs by inflammatory cytokines results in strikingly increased expression and secretion of the protease Cathepsin S (CTSS). We have been characterizing a potential role for CTSS in MSC-mediated angiogenesis through liberation of matrix-bound angiogenic factors and/or through matrix remodeling to create conduits for new blood vessels. However, there are currently no adequate tools to investigate these mechanisms ex vivo. In this talk, I will describe our efforts to leverage the de novo matrix-production capacity of MSCs to synthesize functional 3D basement membrane models in a scaffold-free system, devoid of animal components. These human, biomimetic matrix scaffolds will allow us to decouple and study the molecular mechanisms of extracellular matrix signaling and remodeling during MSC-mediated angiogenesis, and have potential utility for many other applications.