Abstract
Background. Our earlier works showed the quick vascularization of mouse skin grafted Bombyx mori 3D silk fibroin nonwoven scaffolds (3D-SFnws) and the release of exosomes enriched in angiogenic/growth factors (AGFs) from in vitro 3D-SFnws-stuck human dermal fibroblasts (HDFs). Here, we explored whether coronary artery adult human smooth muscle cells (AHSMCs) also release AGFs-enriched exosomes when cultured on 3D-SFnws in vitro. Methods. Media with exosome-depleted FBS served for AHSMCs and human endothelial cells (HECs) cultures on 3D-SFnws or polystyrene. Biochemical methods and double-antibody arrays assessed cell growth, metabolism, and intracellular TGF-β and NF-κB signalling pathways activation. AGFs conveyed by CD9+/CD81+ exosomes released from AHSMCs were double-antibody array analysed and their angiogenic power evaluated on HECs in vitro. Results. AHSMCs grew and consumed D-glucose more intensely and showed a stronger phosphorylation/activation of TAK-1, SMAD-1/-2/-4/-5, ATF-2, c-JUN, ATM, CREB, and an IκBα phosphorylation/inactivation on SFnws vs. polystyrene, consistent overall with a proliferative/secretory phenotype. SFnws-stuck AHSMCs also released exosomes richer in IL-1α/-2/-4/-6/-8; bFGF; GM-CSF; and GRO-α/-β/-γ, which strongly stimulated HECs’ growth, migration, and tubes/nodes assembly in vitro. Conclusions. Altogether, the intensified AGFs exosomal release from 3D-SFnws-attached AHSMCs and HDFs could advance grafts’ colonization, vascularization, and take in vivo—noteworthy assets for prospective clinical applications.
Highlights
Various insect and arthropod species synthesize complex structural proteins, generically named fibroins [1]
The present results reveal that adult human smooth muscle cells (AHSMCs) cultured on the same C/HE-3D-scaffolds structured as 3D nonwovens (SFnws) as above released exosomes carrying 15 angiogenic/growth factors (AGFs), of which 8 were significantly enriched
The AHSMCs exosomes powerfully stimulated human endothelial cells (HECs) to grow, migrate, and form dense tubes and nodes in vitro. Only six of these AGFs, i.e., GrowthRegulated Oncogene (GRO)-α/CXCL1, GRO-β/CXCL2, GRO-γ/CXCL3, IL-8/CXCL8, IL-4, and IL-1α, were significantly enriched in the exosomes released from both AHSMCs and human dermal fibroblasts (HDFs) [16] cultured on C/HE-3D-SFnws
Summary
Various insect and arthropod species synthesize complex structural proteins, generically named fibroins [1]. In relation to translational medicine, another hidden advantage proper of three-dimensional (3D) SF scaffolds is that humans have well over 50 proteins carrying significant stretches of conserved amino acid sequences present in Bombyx mori’s SF. This evolutionary relationship is at the root of the remarkable biocompatibility and lack of immunogenicity of the SF scaffolds [10,11,12]. Our earlier works showed the quick vascularization of mouse skin grafted Bombyx mori 3D silk fibroin nonwoven scaffolds (3D-SFnws) and the release of exosomes enriched in angiogenic/growth factors (AGFs) from in vitro 3D-SFnws-stuck human dermal fibroblasts (HDFs). The intensified AGFs exosomal release from 3D-SFnws-attached AHSMCs and HDFs could advance grafts’ colonization, vascularization, and take in vivo—noteworthy assets for prospective clinical applications
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