Granulocyte‐macrophage colony‐stimulating factor: Conductor of the wound healing orchestra?

Abstract

Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is a glycoprotein and is derived from both hemopoietic and nonhemopoietic sources which exert immunomodulatory properties. Various theories have been proposed to explain why some wounds become chronic and non‐healing. Generalized suppression of inflammation locally or systemically may impede the body's physiological healing response by crippling the activity of reparative cells within the wound ecosystem. Thus, highlighting the importance of promoting host‐directed therapeutics with immunomodulatory properties. The temporal and spatial expression of GM‐CSF and GM‐CSF receptors in the integumentary system suggests that epithelial‐derived GM‐CSF functions in an autocrine/paracrine manner. This may positively affect wound healing physiology via local inflammatory regulation promoting macrophage survival. Although diabetes negatively affects multiple aspects of wound healing GM‐CSF activation is particularly impacted. Compared to acute/healthy wounds diabetic foot ulcers (DFU) only partially activate GM‐CSF activity. There is a deleterious chain of events associated with this unfortunate sequala. DFUs also have a high proportion of monocytes and an absence of activated macrophages which results in an impaired inflammatory response. This may potentially serve as a vital point for GM‐CSF to act as a companion diagnostic/theragnostic modality to help modulate the inflammatory response in wound healing. Correcting macrophage immune dysfunction with exogenous GM‐CSF may help restore the immune balance in the wound ecosystem and jumpstart the wound healing cascade. Thus, the recognized beneficial role of GM‐CSF in immune regulation across many studies provides a rationale for the initiation of the ongoing randomized controlled trials using GM‐CSF.

Engineered exosomes as a prospective therapy for diabetic foot ulcers

“…However, a high-glucose environment has been shown to hinder re-epithelialization by impairing the migration of both keratinocytes and fibroblasts [ 34 , 35 ]. While various growth factors like epidermal growth factor [ 227 ], fibroblast growth factor (FGF) [ 228 ] and granulocyte-macrophage colony-stimulating factor [ 229 ], have been developed for diabetic wound treatment, their therapeutic efficiency is often limited, possibly due to their short half-life and alteration of downstream signal pathways influenced by the cellular and molecular heterogeneity of wounded tissue [ 230 , 231 ]. In this context, exosomes offer an advantageous platform for encapsulating therapeutic growth factors, given their ability to carry diverse cargo and protect it from enzymatic degradation.…”

How to enhance the effects of Platelet Rich Plasma on tissue regeneration: AMPLEX PLUS technology, a new strategy.

“…It increases re-epithelialization, recruiting neutrophils, monocytes and lymphocytes and it stimulates phagocytosis in matured leucocytes. GM-CSF increases angiogenesis and lymphangiogenesis [36,37]. GM-CSF is undetectable in blood (Fig.…”

ROS-scavenging materials for skin wound healing: advancements and applications

“…After necrotic tissue and pathogens are removed, neutrophil proliferation is reduced and forced out of the wound. At the same time, the phenotype of macrophages also gradually changed from M1 type, which promoted the release of inflammatory factors, to M2 type, which promoted angiogenesis and tissue regeneration, and wound repair also entered the proliferative stage ( Chen C. et al, 2023 ; Ead and Armstrong, 2023 ). During the proliferation stage, epithelial cells and fibroblasts undergo active proliferation and migration, gradually filling the exposed wound by forming granulation tissue.…”