Objective-We hypothesized that adipose tissue may contain progenitors cells with cutaneous and angiogenic potential. Methods and Results-Adipose tissue-derived stroma cells (ADSCs) were administrated to skin punched wounds of both nonirradiated and irradiated mice (20 Gy, locally). At day14, ADSCs promoted dermal wound healing and enhanced wound closure, viscolesticity, and collagen tissue secretion in both irradiated and nonirradiated mice. Interestingly, GFP-positive ADSCs incorporated in dermal and epidermal tissue in vivo and expressed epidermal markers K5 and K14. Cultured ADSCs in keratinocyte medium have been shown to differentiate into K5-and K14-positive cells and produced high levels of KGF. At Day 7, ADSCs also improved skin blood perfusion assessed by laser Doppler imaging, capillary density, and VEGF plasma levels in both irradiated and nonirradiated animals. GFP-positive ADSCs incorporated into capillary structures in vivo and expressed the endothelial cell marker CD31. Finally, in situ interphase fluorescence hybridization showed that a small number of ADSCs have the potential to fuse with endogenous keratinocytes. Conclusion-ADSCs
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.
Fibrosis is the endpoint of many chronic inflammatory diseases and is defined by an abnormal accumulation of extracellular matrix components. Despite its slow progression, it leads to organ malfunction. Fibrosis can affect almost any tissue. Due to its high frequency, in particular in the heart, lungs, liver, and kidneys, many studies have been conducted to find satisfactory treatments. Despite these efforts, current fibrosis management therapies either are insufficiently effective or induce severe adverse effects. In the light of these facts, innovative experimental therapies are being investigated. Among these, cell therapy is regarded as one of the best candidates. In particular, mesenchymal stromal cells (MSCs) have great potential in the treatment of inflammatory diseases. The value of their immunomodulatory effects and their ability to act on profibrotic factors such as oxidative stress, hypoxia, and the transforming growth factor-β1 pathway has already been highlighted in preclinical and clinical studies. Furthermore, their propensity to act depending on the microenvironment surrounding them enhances their curative properties. In this paper, we review a large range of studies addressing the use of MSCs in the treatment of fibrotic diseases. The results reported here suggest that MSCs have antifibrotic potential for several organs.
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