The role of cluster of differentiation 163-positive macrophages in wound healing: a preliminary study and a systematic review

This is a literature assessment of essential information and current knowledge that pertains to the potential role for cluster of differentiation (CD) 163+ macrophages in different wound healing models, including extremely rapid tissue regeneration for regenerative medicine purposes. We intend to focus on the beneficial strategies that activate macrophage performance in order to advance the CD163⁺ macrophage-based therapy approaches to accelerate wound healing. We conducted an extensive literature search of peer reviewed articles obtained from the PubMed, Google Scholar, Scopus, Web of Science, and Cochrane databases by using the keywords “wound healing, CD163⁺ macrophages, diabetes mellitus, and burn.” There were no limitations in terms of publication date. Our search resulted in 300 papers from which 17 articles were screened according to the inclusion criteria. We divided the selected articles into four distinct groups: healthy humans (n = 5); healthy animals (n = 7); humans with diabetes (n = 2); and animals with diabetes (n = 3). CD163 is a biomarker of the M2c macrophage subtype in mammals. Functions of M2c macrophages include angiogenesis, matrix maturation, and phagocytosis, and they activate prior to wounding. M2c produces many cytokines and growth factors, and also contains receptors for numerous cytokines and growth factors. Induction of M2c macrophages from tissue-resident macrophages in the wound bed by a suitable agent, such as delivery of intracellular ATP, appears to induce rapid granulation tissue formation without hypertrophic scarring and significantly reduces the lag time of the wound healing process.