Tissue-engineered dermo-epidermal skin grafts prevascularized with adipose-derived cells

The major problem in skin grafting is that tissue-engineered skin grafts after their transplantation are initially entirely dependent on diffusion. Since this process is slow and inefficient, nutrients, growth factors, and oxygen will insufficiently be supplied and the regenerating graft will undergo a physiological crisis, resulting in scar-like dermal structures and shrinkage. The tissue-engineering of a vascular network in human dermo-epidermal skin substitutes (DESS) is a promising approach to overcome this limitation. Here we report, for the first time, on the use of the adipose stromal vascular fraction (SVF)-derived endothelial cell population to tissue-engineer DESS containing a highly efficient capillary plexus. To develop vascular networks in vitro, we employed optimized 3D fibrin or collagen type I hydrogel systems. Upon transplantation onto immune-deficient rats, these pre-formed vascular networks anastomosed to the recipient's vasculature within only four days. As a consequence, the neo-epidermis efficiently established tissue homeostasis, the dermis underwent almost no contraction, and showed sustained epidermal coverage in vivo. Overall, the here described rapid and efficient perfusion of SVF-based skin grafts opens new perspectives for the treatment of hitherto unmet clinical needs in burn/plastic surgery and dermatology.     

Rhabdomyosarcoma and rhabdomyoma associated with nevoid basal cell carcinoma syndrome: Local treatment strategy

This article presents the case of a child presenting with a rhabdomyosarcoma associated with a fetal rhabdomyoma in the setting of nevoid basal cell carcinoma syndrome. Oncologic strategy is discussed.     

Prevalence of Thoracic Aortic Aneurysms in Patients with Degenerative Abdominal Aortic Aneurysms: Results from the Prospective ACTA Study

1. Download : Download high-res image (137KB)
2. Download : Download full-size image

     

Glioblastoma invasion and cooption depend on IRE1α endoribonuclease activity

IRE1α is an endoplasmic reticulum (ER)-resident transmembrane signaling protein and a cellular stress sensor. The protein harbors a cytosolic dual kinase/endoribonuclease activity required for adaptive responses to micro-environmental changes. In an orthotopic xenograft model of human glioma, invalidation of IRE1α RNase or/and kinase activities generated tumors with remarkably distinct phenotypes. Contrasting with the extensive angiogenesis observed in tumors derived from control cells, the double kinase/RNase invalidation reprogrammed mesenchymal differentiation of cancer cells and produced avascular and infiltrative glioblastomas with blood vessel co-option. In comparison, selective invalidation of IRE1α RNase did not compromise tumor angiogenesis but still elicited invasive features and vessel co-option. In vitro, IRE1α RNase deficient cells were also endowed with a higher ability to migrate. Constitutive activation of both enzymes led to wild-type-like lesions. The presence of IRE1α, but not its RNase activity, is therefore required for glioblastoma neovascularization, whereas invasion results only from RNase inhibition. In this model, two key mechanisms of tumor progression and cancer cell survival are functionally linked to IRE1α.     

Cardiovascular risk among hypertensive adolescents and the potential benefit of a screen-and-treat strategy

To evaluate whether screening for hypertension should start early in life, information on the risk of diseases associated with the level of blood pressure in childhood or adolescence is needed. The study by Leiba et al. that is reported in the current issue of Pediatric Nephrology demonstrates convincingly that hypertensive adolescents are at higher risk of cardiovascular death than normotensive adolescents. Nevertheless, it can be shown that this excess risk is not sufficient to justify a screen-and-treat strategy. Since the large majority of cardiovascular deaths occur among normotensive adolescents, measures for primordial prevention of cardiovascular diseases could have a much larger impact at the population level.     

Iodized Salt in Cambodia: Trends from 2008 to 2014

Though the consequences of nutritional iodine deficiency have been known for a long time, in Cambodia its elimination has only become a priority in the last 18 years. The Royal Government of Cambodia initiated the National Sub-Committee for Control of Iodine Deficiency Disorders in 1996 to fight this problem. Using three different surveys providing information across all provinces, we examined the compliance of salt iodization in Cambodia over the last 6 years. Salt samples from the 24 provinces were collect at the household level in 2008 (n = 566) and 2011 (n = 1275) and at the market level in 2014 (n = 1862) and analysed through a wavelength spectrophotometer for iodine content. According to the samples collected, the median iodine content significantly dropped from 22 mg/kg (25th/75th percentile: 2/37 mg/kg) in 2011 to 0 mg/kg in 2014 (25th/75th percentile: 0/8.9 mg/kg) (p < 0.001). The proportion of non-iodized salt within our collected salt drastically increased from 22% in 2011 to 62% in 2014 (p < 0.001). Since the international organizations ceased to support the procurement of iodine, the prevalence of salt compliant with the Cambodian declined within our samples. To date, the current levels of iodine added to tested salt are unsatisfactory as 92% of those salts do not meet the government requirements (99.6% of the coarse salt and 82.4% of the fine salt). This inappropriate iodization could illustrate the lack of periodic monitoring and enforcement from government entities. Therefore, government quality inspection should be reinforced to reduce the quantity of salt not meeting the national requirement.