Emerging therapy for improving wound repair of severe radiation burns using local bone marrow-derived stem cell administrations

Abstract

The therapeutic management of severe radiation burns remains a challenging issue today. Conventional surgical treatment including excision, skin autograft, or flap often fails to prevent unpredictable and uncontrolled extension of the radiation‐induced necrotic process. In a recent very severe accidental radiation burn, we demonstrated the efficiency of a new therapeutic approach combining surgery and local cellular therapy using autologous mesenchymal stem cells (MSC), and we confirmed the crucial place of the dose assessment in this medical management. The patient presented a very significant radiation lesion located on the arm, which was first treated by several surgical procedures: iterative excisions, skin graft, latissimus muscle dorsi flap, and forearm radial flap. This conventional surgical therapy was unfortunately inefficient, leading to the use of an innovative cell therapy strategy. Autologous MSC were obtained from three bone marrow collections and were expanded according to a clinical‐grade protocol using platelet‐derived growth factors. A total of five local MSC administrations were performed in combination with skin autograft. After iterative local MSC administrations, the clinical evolution was favorable and no recurrence of radiation inflammatory waves occurred during the patient's 8‐month follow‐up. The benefit of this local cell therapy could be linked to the “drug cell” activity of MSC by modulating the radiation inflammatory processes, as suggested by the decrease in the C‐reactive protein level observed after each MSC administration. The success of this combined treatment leads to new prospects in the medical management of severe radiation burns and more widely in the improvement of wound repair.

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

“…The Ethics Committee of the Service de Santé des Armées (Army Health Department, Ministry of Defense) approved this research on human material. As previously reported [9], bone marrow mononuclear cells (BMMNCs) were isolated from the supernatant of spongy bone fragments, plated at a density of 100 · 10 3 cells/cm 2 , and cultured at 37°C in 95% air and 5% CO 2 in alpha-minimum essential medium (a-MEM) (Macopharma) with 10 mg/mL ciprofloxacin (Ciflox 400 mg/ 200 mL; Bayer Pharma) and 8% human platelet lysate as a source of growth factors. After 3-4 days, nonadherent cells were removed and cultures were again fed with fresh medium.…”

“…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].…”

“…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].…”

“…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].…”

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

“…Application of Stem cell therapies for repair and regeneration has recently been investigated at a clinical level in variously defected or injured tissues (7)(8)(9). Among which stem cells, adipose-derived regenerative cells (ADRCs) can be harvested with a minimally invasive procedure by liposuction procedure through a small incision.…”