Natural Histogel-Based Bio-Scaffolds for Sustaining Angiogenesis in Beige Adipose Tissue

Abstract

In the treatment of obesity and its related disorders, one of the measures adopted is weight reduction by controlling nutrition and increasing physical activity. A valid alternative to restore the physiological function of the human body could be the increase of energy consumption by inducing the browning of adipose tissue. To this purpose, we tested the ability of Histogel, a natural mixture of glycosaminoglycans isolated from animal Wharton jelly, to sustain the differentiation of adipose derived mesenchymal cells (ADSCs) into brown-like cells expressing UCP-1. Differentiated cells show a higher energy metabolism compared to undifferentiated mesenchymal cells. Furthermore, Histogel acts as a pro-angiogenic matrix, induces endothelial cell proliferation and sprouting in a three-dimensional gel in vitro, and stimulates neovascularization when applied in vivo on top of the chicken embryo chorioallantoic membrane or injected subcutaneously in mice. In addition to the pro-angiogenic activity of Histogel, also the ADSC derived beige cells contribute to activating endothelial cells. These data led us to propose Histogel as a promising scaffold for the modulation of the thermogenic behavior of adipose tissue. Indeed, Histogel simultaneously supports the acquisition of brown tissue markers and activates the vasculature process necessary for the correct function of the thermogenic tissue. Thus, Histogel represents a valid candidate for the development of bioscaffolds to increase the amount of brown adipose tissue in patients with metabolic disorders.

The role and mechanism of mitochondrial functions and energy metabolism in the function regulation of the mesenchymal stem cells

“…It has reported that decreased UCP-1 expression in beige adipocytes from AD-MSCs is associated with mitochondrial ROS accumulation during obesity [ 119 ]. Furthermore, during the differentiation of AD-MSCs into brown-like cells, the expression of UCP-1 increased, differentiated cells show a higher energy metabolism compared to undifferentiated mesenchymal cells, indicating that UCP-1 have a significant role in adipogenic differentiation [ 120 ]. In addition, UCP2 can be stimulated by PGC-1α with mitochondrial biogenesis and respiration, suggesting that PGC-1α is an upstream kinase that regulates UCP2 [ 121 ].…”

In Situ DNA/Protein Interaction Assay to Visualize Transcriptional Factor Activation

“…The CAM represents a well-established model to investigate several physiological and pathological processes including angiogenesis, tumor growth and dissemination [ 3 , 7 , 8 , 9 ], gas exchange [ 10 ], and ion transport [ 11 ]. The CAM has been also exploited to study material biocompatibility [ 12 ], selective vascular occlusion therapies [ 13 ], drug distribution, and to perform toxicological analyses [ 14 , 15 ]. The easy access for experimental manipulation and the low cost make this system a valid alternative to other in vivo models [ 16 , 17 ].…”

Adipose-Derived Stromal/Stem Cells

“…This Special Issue covers research articles investigating various adipose tissues as a source for ASC isolation [ 1 , 2 , 3 ], specific cultures methods to enhance proliferation or viability [ 4 , 5 , 6 , 7 ], and the differentiation capacity [ 8 , 9 , 10 , 11 , 12 ]. Furthermore, other studies highlight aspects of various diseases [ 13 , 14 ], the immunosuppressive potential of ASCs and their derivates [ 15 ] or the in vivo tracking of transplanted ASCs [ 16 ].…”

“…Their data indicated that measuring these compounds could be a useful, non-invasive tool for the metabolic monitoring of cells in vitro. Di Somma and co-workers tested the ability of Histogel, a natural mixture of glycosaminoglycans, to sustain the differentiation of ASCs into brown-like cells and brown adipose tissue [ 12 ]. A study by Plava and co-workers identified that ASCs are permanently altered in the presence of tumor breast tissue and have the potential to increase tumor cell invasive ability through the activation of epithelial-to-mesenchymal transition in tumor cells [ 13 ].…”