Skin Radiation-Induced Ulcers
Radiotherapy is increasingly being used to treat numerous human malignancies. Radiation-induced ulcers have secondary, progressive, & irreversible characteristics. Once chronic radiation ulcers are formed, they are difficult to heal because of the reduced blood supply, fibrosis, & impaired cellular repair potential associated with radiation therapy. The clinical manifestations of radiation ulcers are diverse, and ulcer size, location, depth, and basal conditions can vary widely. On histological level, the radiation effect includes, altered molecular signalling & formation of reactive oxygen species cause single stranded DNA breaks that do not repair completely and activate premature senescence or accelerated terminal differentiation. Despite improved resilience of ADSCs through their superior DNA damage repair mechanisms & reduced metabolic demands that protect them from hypoxia & subsequent apoptosis, studies have demonstrated that radiotherapy adversely affects ADSCs, necessitating the introduction of non-irradiated progenitor cells from distant donor sites. Fat transfer in radiotherapy patients is further complicated by the fact that irradiated recipient sites have unfavourable microenvironments for graft survival because of hypoxia & chronic inflammatory states. Furthermore, stem cells within the injured area recruit myofibroblast like cells, which in turn contribute to fibrosis.
ADSCS has proven by all experiments its superior survival capacity compared to other cellular components of fat grafts, through utilization of anaerobic metabolism, but the sub-lethal RTX-induced injuries impair ADSC proliferation capacity, responsiveness to environmental differentiation cues and alter the ADSC paracrine secretory profile. Such functional alterations in injured ADSCs may account for the inability of local ADSCs to replenish surrounding tissue following radiotherapy injury, thus necessitating the introduction of unirradiated fat (enriched with ADSCs) in the form of a fat graft. These functional ADSCs may reverse radiation injury by restoring the normal proliferative and differentiation capacity of the local ADSC population – Shukla, 2015
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