Matrix-bound nanovesicles within ECM bioscaffolds

Abstract

Matrix-bound vesicles within ECM bioscaffolds provide mechanistic insight into inductive properties.

Long-term retention of ECM hydrogel after implantation into a sub-acute stroke cavity reduces lesion volume

“…A variety of growth factors are also retained within the ECM preparation, including transforming growth factor-β, vascular endothelial growth factor-A, basic fibroblast growth factor, and nerve growth factor [21], which all are known to influence neuronal and endothelial cells. In addition, matrix-bound nanovesicles (MBV) enriched in miRNA and other signaling molecules are present within the ECM preparation [33]. …”

Biologic Scaffolds

“…A cryptic peptide derived from collagen IIIa showed chemotactic activity for many cells, including cortical neural stem cell and myoblasts in vitro and for cells showing stem-cell markers in vivo (Agrawal et al 2011b). Induction of both proliferation and differentiation of neural stem cells by UBM-ECM has been shown (Wang et al 2013a), and neural cell differentiation was later reproduced in neuroblastoma cells with MBVs isolated from UBM-ECM (Huleihel et al 2016). Primitive precursor cells seeded in decellularized kidney proliferated and expressed markers for site-appropriate differentiation (Ross et al 2009).…”

“…MBVs are extracellular vesicles from 10 nm to 600 nm in size embedded within the ECM. MBVs are highly stable bodies that protect their microRNA (miRNA) cargo from degradation and are resistant to the enzymes and detergents used in tissue decellularization protocols (Huleihel et al 2016). miRNAs are small noncoding single-stranded RNA molecules of around 22 nucleotides in length that affect multiple biological processes through posttranscriptional gene regulation (Ling et al 2013 (Huleihel et al 2016).…”

“…The fundamental difference between these bioscaffolds composed of intact ECM and the above-mentioned scaffolds composed of individual matrix molecules is the retention of both the complex mixture of structural and functional ECM molecules and the native three-dimensional ultrastructure. Recognition of the natural ligand landscape and three-dimensional matrix ultrastructure of the ECM by responding host cells initiates scaffold degradation and the subsequent exposure, release, and/or formation of effector molecules such as embedded growth factor (GF), matrix-bound vesicles (MBVs) (Huleihel et al 2016), cytokines, and chemokines. These signaling molecules can have profound biologic activity, including the recruitment of endogenous stem/progenitor cells Reing et al 2009;Crapo et al 2014) and the modulation of the innate immune response (Brown and Badylak 2014), the sum of which facilitates a constructive and functional remodeling outcome.…”

Wound Repair and Regeneration

“…Interestingly, EVs catalyse the crosslinking of collagen in the ECM via lysyl oxidase-like 2 (LOXL2), which is located on the exterior of the exosome membrane [126]. In addition, a study by Huleihel et al (2016) observed that EVs present within the ECM were closely associated with the collagen network of the matrix, but these EVs could be separated from the fibre network [127]. This may indicate that EVs attend to the ECM formation and function.…”