Cell therapy of burns

Abstract

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. Severe burns and their treatmentBurns are traumatic destruction of the skin and sometimes underlying tissues, usually caused by a heat source, less often by electricity or chemicals and rarely by ionizing radiation.1 Necrosis-triggered release of inflammatory mediators and in situ formation of toxic lipid-protein complexes generate local inflammation. In the most severe cases, potentially lethal acute toxaemia with systemic inflammatory response (SIR) and organ dysfunction, with a threshold around 20-30% total body surface area burnt, and dose (burn depth and extension)-dependent severity (1). Severe burns evolve in three phases:• In the early shock phase, hyperinflammation causes intense plasma leakage into the interstitium, organ dysfunction and injury aggravation. • In the following hypermetabolic phase, a long-lasting inflammatory status sustains organ dysfunctions and slows the wound-healing process, while cell-mediated immunity is impaired. • In the late local remodelling phase, cell ⁄ matrix interactions promote fibrotic, hypertrophic and ⁄ or retractile scarring.Besides aggressive supportive therapy, treating burns demands that the toxic eschar be quickly removed and that structure and function of the destroyed skin be restored. This is usually achieved through surgical eschar excision and split thickness autografts from healthy skin areas of the same patient. Despite providing epidermis and also a thin layer of dermal tissue, that technique cannot restore fully functional dermis nor epidermal appendages, and its applicability is limited by available amounts of healthy skin still present. Thus, burn treatment strategies often involve a combination of mesh expanded epidermal autografts, temporary or preparative skin substitutes including skin allografts and bio-engineered products (2), topical treatments and techniques to improve wound healing, and cell therapy in selected cases. Cell therapy for burns: background

Retracted: Use of Decellularized Scaffolds Combined with Hyaluronic Acid and Basic Fibroblast Growth Factor for Skin Tissue Engineering

“…In recent years, a variety of skin substitutes was used in clinic and increased the cure rate of burn of a large and deep skin area. 12,18,35,36 Currently, xenogeneic skin and xenogeneic decellularized dermal matrix were used in the clinic. Although xenogeneic skin has a high degree of similarity with human skin, it is immunogenic to cause immune rejection after implantation and may spread infectious agents, such as viruses and bacteria.…”

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

“…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 stem cells for personalised medicine

“…Initial analysis of treated-patients shows a very encouraging improvement in their systolic function, but only large and properly controlled clinical trials will tell whether this is indeed a major breakthrough in personalised regenerative medicine. Much progress has also been made in the use of stem cell-based approaches for repairing extensive skin burns and critical size skeletal defects over the past few years, although many hurdles have still to be overcome [46,47].…”