Granados M, Morticelli L, Andriopoulou S, Kalozoumis P, Pflaum M, et al.
Journal of cardiovascular translational research •
Decellularized scaffolds represent a promising alternative for mitral valve (MV) replacement. This work developed and characterized a protocol for the decellularization of whole MVs. Porcine MVs were decellularized with 0.5% (w/v) SDS and 0.5% (w/v) SD and sterilized with 0.1% (v/v) PAA. Decellularized samples were seeded with human foreskin fibroblasts and human adipose-derived stem cells to investigate cellular repopulation and infiltration, and with human colony-forming endothelial cells to investigate collagen IV formation. Histology revealed an acellular scaffold with a generally conserved histoarchitecture, but collagen IV loss. Following decellularization, no significant changes were observed in the hydroxyproline content, but there was a significant reduction in the glycosaminoglycan content. SEM/TEM analysis confirmed cellular removal and loss of some extracellular matrix components. Collagen and elastin were generally preserved. The endothelial cells produced newly formed collagen IV on the non-cytotoxic scaffold. The protocol produced acellular scaffolds with generally preserved histoarchitecture, biochemistry, and biomechanics.
It is now generally accepted that the human body exists in close synergy with the gut microbiome and that this cross-talk plays an essential role in human health and disease. One facet from the many interactions between the microbiome and the immune system is the induction of natural antibodies to commensal bacterial glycans, such as blood group antigens, the alpha-Gal epitope or the Thomsen-Friedenreich (TFα) antigen. Since we have observed that certain species of the commensal genus Bacteroides express the TFα antigen, we examined whether the oral dietary supplementation of a pasteurised Bacteroides xylanisolvens strain might be able to enhance the level of natural anti-TFα antibodies in healthy adults. The data obtained from a double-blind, placebo-controlled study involving 140 healthy volunteers and lasting 8 weeks revealed that the oral uptake of this strain was indeed able to increase the level of TFα-specific immunoglobulin M serum antibodies. The effect was dose-dependent but remained - at any doses - within the physiological range determined before intervention. Furthermore, the effect reverted after stopping the intake. The results support the idea of the microbiome inducing the generation of systemic antigen-specific antibodies against sugar epitopes. They also demonstrate the possibility to modulate essential regulatory or defence processes through dietary supplementation of selected commensal bacteria with the aim to assist human health.
