ABSTRACT
Radiotherapy is an invaluable weapon when treating cancer. However, the deleterious effects of radiation, both immediate and long-term, may have a significant effect on local tissues. Problematic wound healing in radiation-damaged tissue constitutes a major problem that is frequently overlooked during the management of patients who require radiotherapy, or have had radiotherapy in the past. Poor wound healing may lead to chronic ulceration, pain, secondary infection and psychological distress and compromise the outcome of general or reconstructive surgery. We discuss the pathophysiology of poor wound healing following radiotherapy, specific problems for radiation-damaged tissue and potential treatments to improve wound healing of irradiated tissues.
Subject(s)
Radiation Injuries/physiopathology , Radiotherapy/adverse effects , Wound Healing/physiology , Wound Healing/radiation effects , Humans , Radiation Injuries/etiology , Radiation Injuries/therapy , Skin Ulcer/etiology , Skin Ulcer/physiopathology , Skin Ulcer/therapyABSTRACT
Neural crest stem cells (NCSCs) persist in peripheral nerves throughout late gestation but their function is unknown. Current models of nerve development only consider the generation of Schwann cells from neural crest, but the presence of NCSCs raises the possibility of multilineage differentiation. We performed Cre-recombinase fate mapping to determine which nerve cells are neural crest derived. Endoneurial fibroblasts, in addition to myelinating and non-myelinating Schwann cells, were neural crest derived, whereas perineurial cells, pericytes and endothelial cells were not. This identified endoneurial fibroblasts as a novel neural crest derivative, and demonstrated that trunk neural crest does give rise to fibroblasts in vivo, consistent with previous studies of trunk NCSCs in culture. The multilineage differentiation of NCSCs into glial and non-glial derivatives in the developing nerve appears to be regulated by neuregulin, notch ligands, and bone morphogenic proteins, as these factors are expressed in the developing nerve, and cause nerve NCSCs to generate Schwann cells and fibroblasts, but not neurons, in culture. Nerve development is thus more complex than was previously thought, involving NCSC self-renewal, lineage commitment and multilineage differentiation.
