Severe burns remain a life-threatening local and general inflammatory condition often with serious sequelae, despite remarkable progress in their treatment over the past three decades. Cultured epidermal autografts, the first and still most up-to-date cell therapy for burns, plays a key role in that progress, but drawbacks to this need to be reduced by using cultured dermal-epidermal substitutes. This review focuses on what could be, in our view, the next major breakthrough in cell therapy of burns -use of mesenchymal stromal cells (MSCs). After summarizing current knowledge, including our own clinical experience with MSCs in the pioneering field of cell therapy of radiation-induced burns, we discuss the strong rationale supporting potential interest in MSCs in treatment of thermal burns, including limited but promising pre-clinical and clinical data in wound healing and acute inflammatory conditions other than burns. Practical options for future therapeutic applications of MSCs for burns treatment, are finally considered. Severe burns and their treatmentBurns are traumatic destruction of the skin and sometimes underlying tissues, usually caused by a heat source, less often by electricity or chemicals and rarely by ionizing radiation.1 Necrosis-triggered release of inflammatory mediators and in situ formation of toxic lipid-protein complexes generate local inflammation. In the most severe cases, potentially lethal acute toxaemia with systemic inflammatory response (SIR) and organ dysfunction, with a threshold around 20-30% total body surface area burnt, and dose (burn depth and extension)-dependent severity (1). Severe burns evolve in three phases:• In the early shock phase, hyperinflammation causes intense plasma leakage into the interstitium, organ dysfunction and injury aggravation. • In the following hypermetabolic phase, a long-lasting inflammatory status sustains organ dysfunctions and slows the wound-healing process, while cell-mediated immunity is impaired. • In the late local remodelling phase, cell ⁄ matrix interactions promote fibrotic, hypertrophic and ⁄ or retractile scarring.Besides aggressive supportive therapy, treating burns demands that the toxic eschar be quickly removed and that structure and function of the destroyed skin be restored. This is usually achieved through surgical eschar excision and split thickness autografts from healthy skin areas of the same patient. Despite providing epidermis and also a thin layer of dermal tissue, that technique cannot restore fully functional dermis nor epidermal appendages, and its applicability is limited by available amounts of healthy skin still present. Thus, burn treatment strategies often involve a combination of mesh expanded epidermal autografts, temporary or preparative skin substitutes including skin allografts and bio-engineered products (2), topical treatments and techniques to improve wound healing, and cell therapy in selected cases. Cell therapy for burns: background
Use of the interface dressing in combination with TNP substantially reduced the pain caused by dressing changes. It therefore makes more acceptable the use of this technique, which aims to optimise the management of wounds that are sometimes considered to be in a therapeutic impasse.
Local acute radiation syndrome (radioepidermitis) mainly affects the skin and superficial tissues. MRI findings correspond with clinical stage (with a strong negative predictive value). MRI outperformed X-ray examination for the diagnosis of bone radionecrosis. Diffusion-weighted imaging shows low ADC in bone and soft tissue necrosis. Perfusion sequence allows assessment of tissue microcirculation impairment.
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