Cellular Mechanisms in Acute and Chronic Wounds after PDT Therapy: An Update

Abstract

PDT is a two-stage treatment that combines light energy with a photosensitizer designed to destroy cancerous and precancerous cells after light activation. Photosensitizers are activated by a specific wavelength of light energy, usually from a laser. The photosensitizer is nontoxic until it is activated by light. However, after light activation, the photosensitizer becomes toxic to the targeted tissue. Among sensitizers, the topical use of ALA, a natural precursor of protoporphyrin IX, a precursor of the heme group, and a powerful photosensitizing agent, represents a turning point for PDT in the dermatological field, as it easily absorbable by the skin. Wound healing requires a complex interaction and coordination of different cells and molecules. Any alteration in these highly coordinated events can lead to either delayed or excessive healing. The goal of this review is to elucidate the cellular mechanisms involved, upon treatment with ALA-PDT, in chronic wounds, which are often associated with social isolation and high costs in terms of care.

Keywords: 5-aminolevulinic acid (ALA); acute wounds; angiogenesis; cellular infiltrate; chronic wounds; mast cells; nerves; neurons; photodynamic therapy; wound healing.

Figure 1

(A) Fvasconcellos (own work): Structural diagram of aminolevulinic acid. Created using ACD/ChemSketch 10.0 and Inkscape. This image of a simple structural formula is ineligible for copyright and, therefore, is in the public domain, because it contains no original authorship. (B) Fvasconcellos (own work): Skeletal formula of protoporphyrin IX. Created using ACD/ChemSketch 10.0 and Inkscape. The copyright holder of this work has released it into the public domain. This standard applies worldwide. In some countries this may not be legally possible. I grant anyone the right to use this work for any purpose, without any conditions, unless such conditions are required by law. (C) Chronic wound: Increased thickness of the epidermis and richness of cellular infiltrate. Hematoxylin Eosin, Light microscopy, scale bar = 10 microns. (D) Colocalization between MCs (stained with avidin, in red) and fibroblasts (stained with HSP47, in green) in PDT-treated chronic wounds. Fluorescence microscopy, scale bar =10 microns (see Table 1 for others information). (E) Colocalization between MCs (stained with avidin, in red) and DCs (stained with MHC class II, in green) in PDT-treated chronic wounds. Fluorescence microscopy, scale bar =10 microns (see Table 1 for others information).