Adipocyte regulation of cancer stem cells.

Cancer stem cells (CSCs) are a highly tumorigenic subpopulation of the cancer cells within a tumor that drive tumor initiation, progression, and therapy resistance. In general, stem cell niche provides a specific microenvironment in which stem cells are present in an undifferentiated and self-renewable state. CSC niche is a specialized tumor microenvironment for CSCs which provides cues for their maintenance and propagation. However, molecular mechanisms for the CSC-niche interaction remain to be elucidated. We have revealed that adipsin (complement factor D) and its downstream effector hepatocyte growth factor are secreted from adipocytes and enhance the CSC properties in breast cancers in which tumor initiation and progression are constantly associated with the surrounding adipose tissue. Considering that obesity, characterized by excess adipose tissue, is associated with an increased risk of multiple cancers, it is reasonably speculated that adipocyte-CSC interaction is similarly involved in many types of cancers, such as pancreas, colorectal, and ovarian cancers. In this review, various molecular mechanisms by which adipocytes regulate CSCs, including secretion of adipokines, extracellular matrix production, biosynthesis of estrogen, metabolism, and exosome, are discussed. Uncovering the roles of adipocytes in the CSC niche will propose novel strategies to treat cancers, especially those whose progression is linked to obesity.

Development of a vascular substitute produced by weaving yarn made from human amniotic membrane.

Because synthetic vascular prostheses perform poorly in small-diameter revascularization, biological vascular substitutes are being developed as an alternative. Although theirin vivoresults are promising, their production involves long, complex, and expensive tissue engineering methods. To overcome these limitations, we propose an innovative approach that combines the human amniotic membrane (HAM), which is a widely available and cost-effective biological raw material, with a rapid and robust textile-inspired assembly strategy. Fetal membranes were collected after cesarean deliveries at term. Once isolated by dissection, HAM sheets were cut into ribbons that could be further processed by twisting into threads. Characterization of the HAM yarns (both ribbons and threads) showed that their physical and mechanical properties could be easily tuned. Since our clinical strategy will be to provide an off-the-shelf allogeneic implant, we studied the effects of decellularization and/or gamma sterilization on the histological, mechanical, and biological properties of HAM ribbons. Gamma irradiation of hydrated HAMs, with or without decellularization, did not interfere with the ability of the matrix to support endothelium formationin vitro. Finally, our HAM-based, woven tissue-engineered vascular grafts (TEVGs) exhibited clinically relevant mechanical properties. Thus, this study demonstrates that human, completely biological, allogeneic, small-diameter TEVGs can be produced from HAM, thereby avoiding costly cell culture and bioreactors.

Influence of material properties and boundary conditions on patient-specific models.

Patient-specific finite element models (PSFEM) are becoming more and more used. Different methods for assigning their material properties were studied on PSFEMs of 9 tibias along with the minimal required length of the CT acquisition window. Material properties are generally attributed to the PSFEM using relationships linking the grayscale of CT scans to the elasticity moduli. Using cortical-specific and trabecular-specific relationships or a generic one, did not result in significant differences. However, the use of homogeneous elastic moduli in the cortical and trabecular regions led to considerable differences. The result highlight that the PSFEM must comprise at least 40% of the tibia to ensure consistent results in the proximal 20%.