New Approach to Radiation Burn treatment by Dosimetry-Guided Surgery Combined with Autologous Mesenchymal Stem Cell Therapy

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.

Therapeutic Potential of Gingival Fibroblasts for Cutaneous Radiation Syndrome: Comparison to Bone Marrow-Mesenchymal Stem Cell Grafts

“…The clinical benefits of local MSC grafts in promoting healing of radiation burn lesions have been demonstrated in several different preclinical models [7,8] and in humans [5,9]. The healing of skin wounds involves complex interactions between different cell types, including fibroblasts and epithelial, endothelial, and inflammatory cells, ECM molecules, growth factors, and cytokines [4].…”

“…More recent studies of wound healing have focused on mesenchymal stem cells (MSCs)-nonhematopoietic, adherent fibroblast-like cells with intrinsic capacity for self-renewal and differentiation-as a possible cell population within the bone marrow that might contribute to cutaneous repair, particularly in radiation burns [4][5][6][7][8][9][10][11].…”

“…GFs can be harvested easily and less invasively from gingival mucosa than MSCs obtained from bone marrow. In this study, we investigated the ability of GFs to promote the healing of cutaneous radiation burns and compared it to the reference MSC treatment [5,9].…”

Autologous adipose-derived regenerative cells are effective for chronic intractable radiation injuries

“…Local radiation injuries are caused during medical therapy for malignant tumors (1), heart disease (2), may be accompanied with systemic symptoms of hematologic, neurologic, gastrointestinal symptoms such as neutropenia, thrombocytopenia, fatigability, nausea and diarrhea by contact to the scrap yard radioactive wastes without notice (3) or exposure to the radiation accidents (4) by touching gammagraphy radioactive source by mistake (5). In a cutaneous adverse reaction observed after estimated 15 Gy to 20 Gy dose of radiation caused by fluoroscopic procedure for ablative treatment to supraventricular arrhythmia, painful ulceration developed in four months and extensive plastic surgery was required (2).…”

“…8 people received intravenous GM-CSF treatment, however, 8 of 14 died due to hemorrhage and infection (4). In 2005, Chile, a 27-year-old man picked up a gammagraphy radioactive source ( 192 Ir, 3.3TBq) with his left hand and inserted in his left pocket of the trouser in the buttock resulted severe pain, erythema, swelling and lastly necrosis continued to several weeks (5). Since radiated tissues demonstrate locally decreased or insufficient vascularity and tissue damage, demonstrating erythema, teleangietasia, pigmentation or dermal atrophy, once wound is developed, it is often intractable and further leading to tissue necrosis, infection and later fibrosis in demonstrating chronic radiation injury syndrome (6).…”