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剂量测定引导手术联合自体间充质干细胞疗法治疗放射性烧伤的新方法。

New approach to radiation burn treatment by dosimetry-guided surgery combined with autologous mesenchymal stem cell therapy.

作者信息

Lataillade J J, Doucet C, Bey E, Carsin H, Huet C, Clairand I, Bottollier-Depois J F, Chapel A, Ernou I, Gourven M, Boutin L, Hayden A, Carcamo C, Buglova E, Joussemet M, de Revel T, Gourmelon P

机构信息

Centre de Transfusion Sanguine des Armées, Jean Julliard, Unité de Thérapie Cellulaire, BP 410, 92141 Clamart Cedex, France.

出版信息

Regen Med. 2007 Sep;2(5):785-94. doi: 10.2217/17460751.2.5.785.

Abstract

The therapeutic management of severe radiation burns remains a challenging issue. Conventional surgical treatment (excision and skin autograft or rotation flap) often fails to prevent unpredictable and uncontrolled extension of the radiation necrotic process. We report here an innovative therapeutic strategy applied to the victim of a radiation accident (December 15, 2005) with an iridium gammagraphy radioactive source (192Ir, 3.3 TBq). The approach combined numerical dosimetry-guided surgery with cellular therapy using mesenchymal stem cells. A very severe buttock radiation burn (2000 Gy at the center of the skin surface lesion) of a 27-year-old Chilean victim was widely excised (10 cm in diameter) using a physical and anatomical dose reconstruction in order to better define the limit of the surgical excision in apparently healthy tissues. A secondary extension of the radiation necrosis led to a new excision of fibronecrotic tissues associated with a local cellular therapy using autologous expanded mesenchymal stem cells as a source of trophic factors to promote tissue regeneration. Bone marrow-derived mesenchymal stem cells were expanded according to a clinical-grade technique using closed culture devices and serum-free medium enriched in human platelet lysate. The clinical evolution (radiation pain and healing progression) was favorable and no recurrence of radiation inflammatory waves was observed during the 11 month patient's follow-up. This novel multidisciplinary therapeutic approach combining physical techniques, surgical procedures and cellular therapy with adult stem cells may be of clinical relevance for improving the medical management of severe localized irradiations. It may open new prospects in the field of radiotherapy complications.

摘要

严重放射性烧伤的治疗管理仍然是一个具有挑战性的问题。传统的手术治疗(切除和自体皮肤移植或旋转皮瓣)往往无法防止放射性坏死过程不可预测和不受控制的扩展。我们在此报告一种应用于一名放射性事故受害者(2005年12月15日)的创新治疗策略,该受害者接触了铱γ射线照相放射源(192Ir,3.3太贝克勒尔)。该方法将数值剂量测定引导的手术与使用间充质干细胞的细胞治疗相结合。一名27岁智利受害者的臀部严重放射性烧伤(皮肤表面病变中心剂量为2000戈瑞),通过物理和解剖剂量重建进行了广泛切除(直径10厘米),以便更好地确定在看似健康组织中的手术切除界限。放射性坏死的二次扩展导致对纤维坏死组织进行新的切除,并结合局部细胞治疗,使用自体扩增的间充质干细胞作为营养因子来源以促进组织再生。骨髓来源的间充质干细胞根据临床级技术进行扩增,使用封闭培养装置和富含人血小板裂解物的无血清培养基。临床进展(放射性疼痛和愈合进程)良好,在患者11个月的随访期间未观察到放射性炎症波复发。这种将物理技术、手术程序和成人干细胞细胞治疗相结合的新型多学科治疗方法可能对改善严重局部照射的医疗管理具有临床意义。它可能为放射治疗并发症领域开辟新的前景。

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