New emerging concepts in the medical management of local radiation injury

Institut de Radioprotection et de Sûreté Nucléaire, Laboratoire de Radiopathologie et de Thérapie Expérimentale, BP 17, 92262 Fontenay- aux-Roses, France.
Health physics (Impact Factor: 1.27). 06/2010; 98(6):851-7. DOI: 10.1097/HP.0b013e3181c9f79a
Source: PubMed


Treatment of severe radiation burns remains a difficult medical challenge. The response of the skin to ionizing radiation results in a range of clinical manifestations. The most severe manifestations are highly invalidating. Although several therapeutic strategies (excision, skin grafting, skin or muscle flaps) have been used with some success, none have proven entirely satisfying. The concept that stem cell injections could be used for reducing normal tissue injury has been discussed for a number of years. Mesenchymal stem cells therapy may be a promising therapeutic approach for improving radiation-induced skin and muscle damages. Pre-clinical and clinical benefit of mesenchymal stem cell injection for ulcerated skin and muscle restoration after high dose radiation exposure has been successfully demonstrated. Three first patients suffering from severe radiological syndrome were successfully treated in France based on autologous human grade mesenchymal stem cell injection combined to plastic surgery or skin graft. Stem cell therapy has to be improved to the point that hospitals can put safe, efficient, and reliable clinical protocols into practice.

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    • "Finally, in spite of successful clinical trials using MSCs, there is few data concerning the long-term engraftment and side effects after MSC systemic injections; transplanted stem cells must not form teratomas or undergo transformation and they must not promote tumour recurrence. Clinical trials using MSCs in accidental irradiation [16], late severe damage of irradiation [17] [18], or radiotherapy Stem Cells International [19] [20] of breast cancer allowed for tissue regeneration when other therapies failed [21]. There is more to consider than radiation induced DNA damage and long-term inhibition of growth of exposed cells mediated by P53 and other pathways. "
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    ABSTRACT: There is little information on the fate of infused mesenchymal stem cells (MSCs) and long-term side effects after irradiation exposure. We addressed these questions using human MSCs (hMSCs) intravenously infused to nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice submitted to total body irradiation (TBI) or local irradiation (abdominal or leg irradiation). The animals were sacrificed 3 to 120 days after irradiation and the quantitative and spatial distribution of hMSCs were studied by polymerase chain reaction (PCR). Following their infusion into nonirradiated animals, hMSCs homed to various tissues. Engraftment depended on the dose of irradiation and the area exposed. Total body irradiation induced an increased hMSC engraftment level compared to nonirradiated mice, while local irradiations increased hMSC engraftment locally in the area of irradiation. Long-term engraftment of systemically administered hMSCs in NOD/SCID mice increased significantly in response to tissue injuries produced by local or total body irradiation until 2 weeks then slowly decreased depending on organs and the configuration of irradiation. In all cases, no tissue abnormality or abnormal hMSCs proliferation was observed at 120 days after irradiation. This work supports the safe and efficient use of MSCs by injection as an alternative approach in the short- and long-term treatment of severe complications after radiotherapy for patients refractory to conventional treatments.
    Stem cell International 02/2014; 2014:939275. DOI:10.1155/2014/939275 · 2.81 Impact Factor
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    • "As a matter of fact, in the case of a partial body irradiation (e.g., source handlings, radiotherapy and radiology accidents or sources in a person’s clothes’ pocket), the local dose can be several orders of magnitude higher than the whole body dose. Therefore, in such cases, subsequent assessment of the maximum dose is highly desirable for a competent choice of the therapeutic strategy (Tamarat et al. 2012; Benderitter et al. 2010; Bey et al. 2010). For some scenarios with a good knowledge of accident parameters, it is possible to assess the local dose using numerical simulations; however, in the case of sources-handling, which is a very common type of radiation accident, the applicability of numerical approaches is limited due to the difficulty in reconstructing the irradiation configuration (lack of details). "
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    ABSTRACT: Until very recently, analysis of bone biopsies by means of the method of electron paramagnetic resonance (EPR) collected after surgery or amputation has been considered as the sole reliable method for radiation dose assessment in hands and feet. EPR measurements in finger- and toenail have been considered for accident dosimetry for a long time. Human nails are very attractive biophysical materials because they are easy to collect and pertinent to whole body irradiation. Information on the existence of a radiation-induced signal in human nails has been reported almost 25 years ago. However, no practical application of EPR dosimetry on nails is known to date because, from an EPR perspective, nails represent a very complex material. In addition to the radiation-induced signal (RIS), parasitic and intense signals are induced by the mechanical stress caused when collecting nail samples (mechanically induced signals-MIS). Moreover, it has been demonstrated that the RIS stability is strongly influenced not only by temperature but also by humidity. Most studies of human nails were carried out using conventional X-band microwave band (9 GHz). Higher frequency Q-band (37 GHz) provides higher spectral resolution which allows obtaining more detailed information on the nature of different radicals in human nails. Here, we present for the first time a complete description of the different EPR signals identified in nails including parasitic, intrinsic and RIS. EPR in both X- and Q-bands was used. Four different MIS signals and five different signals specific to irradiation with ionizing radiation have been identified. The most important outcome of this work is the identification of a stable RIS component. In contrast with other identified (unstable) RIS components, this component is thermally and time stable and not affected by the physical contact of fingernails with water. A detailed description of this signal is provided here. The discovery of stable radiation-induced radical(s) associated with the RIS component mentioned opens a way for broad application of EPR dosimetry in human nails. Consequently, several recent dosimetry assessments of real accident cases have been performed based on the described measurements and analyses of this component.
    Biophysik 01/2014; 53(2). DOI:10.1007/s00411-014-0512-2 · 1.53 Impact Factor
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    • "skin is also an attractive potential biodosimeter for the following reasons: It is always in place at the time of radiation exposure, its radiation-induced effects have been studied extensively, it provides information related to nonuniform partial body exposures, it covers the entire body (so that in all but the most extreme accidents, one will have portions of skin undamaged by physical trauma that can be used for screening), and early erythema and cytokine secretion are observed within a few hours after 2Y3 Gy of exposure (Hall and Giaccia 2011; Muller and Meineke 2007). Radiation-induced skin injuries may be related to a number of factors, including superficial arteriolar constriction , capillary vessel dilation, microvasculature reduction , intracellular edema, bullae formation, permeability change, inflammation, remodeling of dermal or epidermal structures, and certain genetic properties (Archambeau et al. 1995; Hadad et al. 2010; Benderitter et al. 2010; Schmuth et al. 2001; Balli et al. 2009). However, other than the early erythema mentioned above, overt clinical symptoms of these radiation-induced skin injuries may take days or weeks to manifest, limiting their usefulness in initiating appropriate preventive and supportive treatments early on. "
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    ABSTRACT: An effective screening technology is needed to triage individuals at the time of radiation incidents involving a large population. Three-dimensional thermal tomography is a relatively new development in active thermal imaging technology that produces cross-sectional images based on the subject's ability to transfer heat-thermal effusivity-at the voxel level. This noninvasive imaging modality has been used successfully in nondestructive examination of complex materials; also it has been shown to predict the severity of radiation-induced skin injuries several days before the manifestation of severe moist desquamations or blister formation symptoms in mice at 40 Gy. If these results are confirmed at lower dose levels in human subjects, a thermal tomography imaging device may be an ideal screening tool in radiation emergencies. This imaging method is non-invasive, relatively simple, easily adaptable for field use, and when properly deployed, it will enhance public emergency preparedness for incidents involving unexpected radiation exposure.
    Health physics 08/2012; 103(2):204-9. DOI:10.1097/HP.0b013e31824758c2 · 1.27 Impact Factor
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