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Leclerc T.,Burn Treatment Center | Leclerc T.,Military Blood Transfusion Center | Thepenier C.,Military Blood Transfusion Center | Jault P.,Burn Treatment Center | And 9 more authors.
Cell Proliferation

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. © 2011 Blackwell Publishing Ltd. Source

Tamarat R.,Institute for Radiological Protection and Nuclear Safety | Lataillade J.J.,Military Blood Transfusion Center | Bey E.,British Petroleum | Gourmelon P.,Institute for Radiological Protection and Nuclear Safety | Benderitter M.,Institute for Radiological Protection and Nuclear Safety
Radiation Protection Dosimetry

Several countries have increased efforts to develop medical countermeasures to protect against radiation toxicity due to acts of bioterrorism as well as cancer treatment. Both acute radiation injuries and delayed effects such as cutaneous effects and impaired wound repair depend, to some extent, on angiogenesis deficiency. Vascular damage influences levels of nutrients, oxygen available to skin tissue and epithelial cell viability. Consequently, the evolution of radiation lesions often becomes uncontrolled and surgery is the final option-amputation leading to a disability. Therefore, the development of strategies designed to promote healing of radiation injuries is a major therapeutic challenge. Adult mesenchymal stem cell therapy has been combined with surgery in some cases and not in others and successfully applied in patients with accidental radiation injuries. Although research in the field of radiation skin injury management has made substantial progress in the past 10 y, several strategies are still needed in order to enhance the beneficial effect of stem cell therapy and to counteract the deleterious effect of an irradiated tissue environment. This review summarises the current and evolving advances concerning basic and translational research based on stem cell therapy for the management of radiological burns. © World Health Organization 2012. All rights reserved. Source

Reyes E.H.,International Atomic Energy Agency | Baciu F.,International Atomic Energy Agency | Benderitter M.,Institute for Radiological Protection and Nuclear Safety | Lataillade J.J.,Military Blood Transfusion Center | And 3 more authors.
Radiation Research

This article provides an overview of four radiological accidents in Latin America, and includes a history of the events, the clinical manifestations and health consequences for the exposed individuals, the medical response based on preclinical studies and the role of the International Atomic Energy Agency (IAEA) in coordinating medical response assistance. © 2016 by Radiation Research Society. Source

Linard C.,Institute for Radiological Protection and Nuclear Safety | Busson E.,Military Blood Transfusion Center | Holler V.,Institute for Radiological Protection and Nuclear Safety | Strup-Perrot C.,Institute for Radiological Protection and Nuclear Safety | And 9 more authors.
Stem Cells Translational Medicine

The management of proctitis in patients who have undergone very-high-dose conformal radiotherapy is extremely challenging. The fibrosis-necrosis, fistulae, and hemorrhage induced by pelvic overirradiation have an impact on morbidity. Augmenting tissue repair by the use of mesenchymal stem cells (MSCs) may be an important advance in treating radiation-induced toxicity. Using a preclinical pig model, we investigated the effect of autologous bone marrow-derived MSCs on high-dose radiation-induced proctitis. Irradiated pigs received repeated intravenous administrations of autologous bone marrow-derived MSCs. Immunostaining and real-time polymerase chain reaction analysis were used to assess the MSCs' effect on inflammation, extracellular matrix remodeling, and angiogenesis, in radiation-induced anorectal and colon damages. In humans, as in pigs, rectal overexposure induces mucosal damage (crypt depletion, macrophage infiltration, and fibrosis). In a pig model, repeated administrations of MSCs controlled systemic inflammation, reduced in situ both expression of inflammatory cytokines and macrophage recruitment, and augmented interleukin-10 expression in rectal mucosa. MSC injections limited radiation-induced fibrosis by reducing collagen deposition and expression of col1a2/col3a1 and transforming growth factor-β/connective tissue growth factor, and by modifying the matrix metalloproteinase/ TIMP balance. In a pig model of proctitis, repeated injections of MSCs effectively reduced inflammation and fibrosis. This treatment represents a promising therapy for radiation-induced severe rectal damage. © AlphaMed Press 2013. Source

Linard C.,Institute for Radiological Protection and Nuclear Safety | Tissedre F.,Military Blood Transfusion Center | Busson E.,Military Blood Transfusion Center | Holler V.,Institute for Radiological Protection and Nuclear Safety | And 8 more authors.
Stem Cells and Development

Mesenchymal stem cell (MSC) therapy has recently been investigated as a potential treatment for cutaneous radiation burns. We tested the hypothesis that injection of local gingival fibroblasts (GFs) would promote healing of radiation burn lesions and compared results with those for MSC transplantation. Human clinical-grade GFs or bone marrow-derived MSCs were intradermally injected into mice 21 days after local leg irradiation. Immunostaining and real-time PCR analysis were used to assess the effects of each treatment on extracellular matrix remodeling and inflammation in skin on days 28 and 50 postirradiation. GFs induced the early development of thick, fully regenerated epidermis, skin appendages, and hair follicles, earlier than MSCs did. The acceleration of wound healing by GFs involved rearrangement of the deposited collagen, modification of the Col/MMP/TIMP balance, and modulation of the expression and localization of tenascin-C and of the expression of growth factors (VEGF, EGF, and FGF7). As MSC treatment did, GF injection decreased the irradiation-induced inflammatory response and switched the differentiation of macrophages toward an M2-like phenotype, characterized by CD163+ macrophage infiltration and strong expression of arginase-1. These findings indicate that GFs are an attractive target for regenerative medicine, for easier to collect, can grow in culture, and promote cutaneous wound healing in irradiation burn lesions. © 2015, Mary Ann Liebert, Inc. Source

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