Cellular and molecular pathology of HTS: basis for treatment.
Hypertrophic scar and keloids are fibroproliferative disorders of the skin which occur often unpredictably, following trauma and inflammation that compromise cosmesis and function and commonly recur following surgical attempts for improvement. Despite decades of research in these fibrotic conditions, current non-surgical methods of treatment are slow, inconvenient and often only partially effective. Fibroblasts from these conditions are activated to produce extracellular matrix proteins such as collagen I and III, proteoglycans such as versican and biglycan and growth factors, including transforming growth factor-beta and insulin like growth factor I. However, more consistently these cells produce less remodeling enzymes including collagenase and other matrix metalloproteinases, as well as the small proteoglycan decorin which is important for normal collagen fibrillogenesis. Recently, the systemic response to injury appears to influence the local healing process whereby increases in Th2 and possibly Th3 cytokines such as IL-2, IL-4 and IL-10 and TGF-beta are present in the circulating lymphocytes in these fibrotic conditions. Finally, unique bone marrow derived cells including mesenchymal and endothelial stem cells as well as fibrocytes appear to traffic into healing wounds and influence the healing tissue. On this background, clinicians are faced with patients who require treatment and the pathophysiologic basis as currently understood is reviewed for a number of emerging modalities.
Armour
Alexis
A
Department of Surgery, University of Alberta Hospital, Edmonton, Alberta, Canada.
Scott
Paul G
PG
Tredget
Edward E
EE
D002454:Cell Differentiation; D017439:Cicatrix, Hypertrophic / Q000378:metabolism* / Q000503:physiopathology* / Q000628:therapy; D016207:Cytokines / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D007249:Inflammation; D014945:Wound Healing
D016207:Cytokines