3D-Printed proangiogenic patches of photo-crosslinked gelatin and polyurethane hydrogels laden with vascular cells for treating vascular ischemic diseases.

Engineering vascularized tissues remains a promising approach for treating ischemic cardiovascular diseases. The availability of 3D-bioprinted vascular grafts that induce therapeutic angiogenesis can help avoid necrosis and excision of ischemic tissues. Here, using a combination of living cells and biodegradable hydrogels, we fabricated 3D-printed biocompatible proangiogenic patches from endothelial cell-laden photo-crosslinked gelatin (EC-PCG) bioink and smooth muscle cell-encapsulated polyurethane (SMC-PU) bioink. Implantation of 3D-bioprinted proangiogenic patches in a mouse model showed that EC-PCG served as an angiogenic capillary bed, whereas patterned SMC-PU increased the density of microvessels. Moreover, the assembled patterns between EC-PCG and SMC-PU induced the geometrically guided generation of microvessels with blood perfusion. In a rodent model of hindlimb ischemia, the vascular patches rescued blood flow to distal tissues, prevented toe/foot necrosis, promoted muscle remodeling, and increased the capillary density, thereby improving the heat-escape behavior of ischemic animals. Thus, our 3D-printed vascular cell-laden bioinks constitute efficient and scalable biomaterials that facilitate the engineering of vascular patches capable of directing therapeutic angiogenesis for treating ischemic vascular diseases.

Effects of supplementation with selenium, as selenized yeast, in a healthy male population from New Zealand.

Selenium (Se) supplementation was tested in a group of healthy men from Auckland, New Zealnd with selenized yeast (Selplex, 200 µg/day) as the supplementation mode. A set of biomarkers, including DNA damage levels and seleno-antioxidant enzyme levels, were evaluated at pre- and postsupplementation time points. Supplementation produced significant increases in serum Se levels, red blood cell (RBC) thioredoxin reductase (TR) activity and peroxide-induced DNA damage, when the mean baseline serum Se level was 110 ng/ml. Those with higher baseline serum Se levels gained less serum Se and showed a significant reduction of RBC glutathione peroxidase (GPx) activity by supplementation. The optimum benefits of supplementation on DNA stability are observed when the serum Se level reaches between >120 and <160 ng/ml. However, the most significant observation was that those with highest baseline DNA damage benefit the most from Se supplementation, whereas those having lower baseline DNA damage are disadvantaged. A dose of 200 µg/day selenized yeast was also shown to be a safer supplementation option compared to a similar dose of selenomethionine (SeMet). This study highlights the requirement for prestratification of a population by standing serum Se level and baseline DNA damage level, before any Se supplementation is carried out.

Let-7b-mediated suppression of basigin expression and metastasis in mouse melanoma cells.

Basigin (Bsg), also called extracellular matrix metalloproteinase inducer (EMMPRIN), is highly expressed on the surface of tumor cells and stimulates adjacent fibroblasts or tumor cells to produce matrix metalloproteinases (mmps). It has been shown that Bsg plays an important role in growth, development, cell differentiation, and tumor progression. MicroRNAs (miRNAs) are a class of short endogenous non-protein coding RNAs of 20-25 nucleotides (nt) that function as post-transcriptional regulators of gene expression by base-pairing to their target mRNAs and thereby mediate cleavage of target mRNAs or translational repression. In this study, let-7b, one of the let-7 family members, was investigated for its effect on the growth and invasiveness of the mouse melanoma cell line B16-F10. We have shown that let-7b can suppress the expression of Bsg in B16-F10 cells and also provided evidence that this suppression could result in the indirect suppression of mmp-9. The ability of B16-F10 cells transfected with let-7b to invade or migrate was significantly reduced. In addition, let-7b transfected B16-F10 cells displayed an inhibition of both cellular proliferation and colony formation. Furthermore, it was shown that the overexpression of let-7b in B16-F10 cells could reduce lung metastasis. Taken together, the present study identifies let-7b as a tumor suppressor that represses cancer cell proliferation and migration as well as tumor metastasis in mouse melanoma cells.