The Protein Kinase A Inhibitor KT5720 Prevents Endothelial Dysfunctions Induced by High-Dose Irradiation.

High-dose irradiation can trigger numerous endothelial dysfunctions, including apoptosis, the overexpression of adhesion molecules, and alteration of adherens junctions. Altogether, these endothelial dysfunctions contribute to the development of tissue inflammation and organ damage. The development of endothelial dysfunctions may depend on protein phosphorylation by various protein kinases, but the possible role of protein kinase A (PKA) has not been investigated so far, and efficient compounds able to protect the endothelium from irradiation effects are needed.

Comparison of Three Antagonists of Hedgehog Pathway to Promote Skeletal Muscle Regeneration after High Dose Irradiation.

The current geopolitical context has brought the radiological nuclear risk to the forefront of concerns. High-dose localized radiation exposure leads to the development of a musculocutaneous radiation syndrome affecting the skin and subcutaneous muscles. Despite the implementation of a gold standard treatment based on an invasive surgical procedure coupled with autologous cell therapy, a muscular defect frequently persists.

Validation of genes for H-ARS severity prediction in leukemia patients - interspecies comparison, challenges, and promises.

Purpose: In a previous baboon-study, a total of 29 genes were identified for clinical outcome prediction of the hematologic, acute, radiation, syndrome (H-ARS) severity. Among them, four genes ( appeared promising and were validated in five leukemia patients. Within this study, we sought further in-vivo validation in a larger number of whole-body irradiated patients.

Nano-Architecture of Persistent Focal DNA Damage Regions in the Minipig Epidermis Weeks after Acute γ-Irradiation.

Exposure to high acute doses of ionizing radiation (IR) can induce cutaneous radiation syndrome. Weeks after such radiation insults, keratinocyte nuclei of the epidermis exhibit persisting genomic lesions that present as focal accumulations of DNA double-strand break (DSB) damage marker proteins. Knowledge about the nanostructure of these genomic lesions is scarce.

In Situ Identification of Both IL-4 and IL-10 Cytokine-Receptor Interactions during Tissue Regeneration.

Cytokines secreted by individual immune cells regulate tissue regeneration and allow communication between various cell types. Cytokines bind to cognate receptors and trigger the healing process. Determining the orchestration of cytokine interactions with their receptors on their cellular targets is essential to fully understanding the process of inflammation and tissue regeneration.

The immunosuppressant drug Cyclosporin A aggravates irradiation effects in endothelial cells.

The immunosuppressant drug Cyclosporin A (CsA) has been widely used to prevent the development of Graft-versus-Host Disease (GvHD) that can occur after transplantation, including allogeneic graft after accidental high-dose irradiation in humans. Here, we show that CsA alone stimulates ICAM-1 overexpression in human pulmonary microvascular endothelial cells (HPMECs) through Toll-Like Receptor 4 (TLR4) and NF-κB activation. In HPMECs, CsA treatment significantly worsened the overexpression of ICAM-1 induced by high-dose irradiation (15 Gy).

Non-Specific Binding, a Limitation of the Immunofluorescence Method to Study Macrophages In Situ.

Advances in understanding tissue regenerative mechanisms require the characterization of in vivo macrophages as those play a fundamental role in this process. This characterization can be approached using the immuno-fluorescence method with widely studied and used pan-markers such as CD206 protein. This work investigated CD206 expression in an irradiated-muscle pig model using three different antibodies.

TRPV4 channel activation induces the transition of venous and arterial endothelial cells toward a pro-inflammatory phenotype.

The Transient Receptor Potential Vanilloid 4 (TRPV4) of endothelial cells contributes to many important functions including the regulation of Ca homeostasis, cell volume, endothelial barrier permeability, and smooth muscle tone. However, its role in the transition of endothelial cells toward a pro-inflammatory phenotype has not been studied so far. Using both arterial and venous endothelial cells, we first show that the pharmacological activation of TRPV4 channels with GSK1016790A, a potent TRPV4 agonist, triggers robust and sustained Ca increases, which are blocked by both TRPV4 antagonists HC067047 and RN9893.

Hybridization-chain-reaction is a relevant method for in situ detection of M2d-like macrophages in a mini-pig model.

Macrophages are a heterogeneous population of cells with an important role in innate immunity and tissue regeneration. Based on in vitro experiments, macrophages have been subdivided into five distinct subtypes named M1, M2a, M2b, M2c, and M2d, depending on the means of their activation and the cell surface markers they display. Whether all subtypes can be detected in vivo is still unclear.

Characterization of macrophages, giant cells and granulomas during muscle regeneration after irradiation.

Macrophages play a fundamental role in the different stages of muscle regeneration although the precise mechanisms involved are not entirely understood. Here we investigated the types of macrophages and cytokines that appeared in muscles after local gamma irradiation of mini-pigs that underwent no subsequent treatment or received three successive adipose tissue-derived stem cell (ASC) injections. Although some variability was observed among the three animals included in each study group, a general picture emerged.

MSC-Derived Extracellular Vesicles: New Emergency Treatment to Limit the Development of Radiation-Induced Hematopoietic Syndrome?

Nuclear accidents or acts of terrorism involving radioactive sources might lead to mass casualties irradiation. The hematopoietic system is one of the most critical and radiation-sensitive tissues because the limited life span of blood cells requires the continuous division of hematopoietic stem cells (HSCs) into the bone marrow. The radiation-induced hematopoietic syndrome, RI-HS, is an impairment of the hematopoiesis that will result in pancytopenia of various degrees.

Bringing Radiation Exposures and Associated Health Risks into Perspective-Development of an App.

The NATO HFM 291 research task group (RTG) on "Ionizing Radiation Bioeffects and Countermeasures" represents a group of scientists from military and civilian academic and scientific institutions primarily working in the field of radiobiology. Among other tasks, the RTG intends to extend their work on risk estimation and communication to bridge the gap in appropriate judgment of health risks given a certain radiation exposure. The group has no explicit psychological background but an expertise in radiobiology and risk assessment.

French Policies for Victim Management During Mass Radiological Accidents/Attacks.

In the current international context, emergency medical services have to be prepared for chemical, biological, radiological, and nuclear events. Emergency response to radiological or nuclear events requires coordination between many components: the fire brigade, emergency medical services (including nurses and physicians), police, hospitals, etc. To optimize efficiency, victim management in France is governed by specific policies and planned responses.

First Insights Into the M2 Inflammatory Response After Adipose-Tissue-Derived Stem Cell Injections in Radiation-Injured Muscles.

The cutaneous radiation syndrome is the clinical consequence of local high-dose irradiation. It is characterized by extensive inflammation, necrosis, and poor revascularization of the skin, resulting in muscle inflammation and fibrosis. Based on these physiopathological processes, subcutaneous injections of adipose-tissue-derived stem/stromal cells have shown favorable effects on skin-wound healing in a minipig model of cutaneous radiation syndrome, in which muscle fibrosis persisted.

Contribution of INTRAMUSCULAR Autologous Adipose Tissue-Derived Stem Cell Injections to Treat Cutaneous Radiation Syndrome: Preliminary Results.

Cutaneous radiation syndrome caused by high dose located irradiation is characterized by delayed symptoms, incomplete wound healing, and poor revascularization. Subcutaneous adipose tissue derived stromal/stem cells have been shown to improve skin repair in a minipig model of cutaneous radiation syndrome despite a subcutaneous defect being a consequence of radio-induced muscular fibrosis. Based on the pro-myogenic potential of stromal/stem cells, a new protocol combining subcutaneous and intramuscular injections was evaluated in a preliminary study.

Transient gene therapy to treat cutaneous radiation syndrome: development in a minipig model.

Cutaneous radiation syndrome is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Adipocyte derived stem cells injection may improve tissue regeneration through secreted factors. Thus mesenchymal stem cells secretome optimization, using transient transfection, may represent a new strategy to treat this syndrome.

Application of adipocyte-derived stem cells in treatment of cutaneous radiation syndrome.

Cutaneous radiation syndrome caused by local high dose irradiation is characterized by delayed outcome and incomplete healing. Recent therapeutic management of accidentally irradiated burn patients has suggested the benefit of local cellular therapy using mesenchymal stem cell grafting. According to the proposed strategy of early treatment, large amounts of stem cells would be necessary in the days following exposure and hospitalization, which would require allogeneic stem cells banking.

Autologous adipocyte derived stem cells favour healing in a minipig model of cutaneous radiation syndrome.

Cutaneous radiation syndrome (CRS) is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Here we examined for the first time in a large animal model the therapeutic potential of autologous adipose tissue-derived stroma cells (ASCs). For experiments, Göttingen minipigs were locally gamma irradiated using a (60)Co source at the dose of 50 Gy and grafted (n = 5) or not (n = 8).