Umbilical cord-derived mesenchymal stem cell secretome promotes skin regeneration and rejuvenation: From mechanism to therapeutics

Abstract

How to effectively repair cutaneous wounds and promote skin rejuvenation has always been a challenging issue for clinical medicine and medical aesthetics. Current conventional medicines exhibit several drawbacks, including limited therapeutic effects, prolonged treatment periods, and high costs. As a novel cell-free therapy, the umbilical cord-derived mesenchymal stem cell (UCMSC) secretome may offer a promising approach for skin regeneration and rejuvenation. The UCMSC secretome is a collection of all proteins secreted by mesenchymal stem cells, including conditioned media, exosomes, and other substances. The UCMSC secretome has numerous abilities to accelerate acute wound healing, including high fibroblast and keratinocyte proliferative activity, pro-angiogenesis, anti-inflammation, anti-fibrosis, and anti-oxidative stress. Its impact on the four stages of wound healing is manifested by inducing the haemostasis phase, inhibiting the inflammation phase, promoting the proliferation phase, and regulating the remodelling phase. Furthermore, it is highly effective in the treatment of chronic wounds, alopecia, aging, and skin homeostasis disturbance. This review focuses on the clinical therapies and application prospects of the UCMSC secretome, encompassing its source, culture, separation, identification, storage, and pretreatment. Additionally, a discussion on the dosage, administration route, efficacy, and biosafety in the clinical situation is presented. This review aims to provide scientific support for the mechanistic investigation and clinical utilisation of the UCMSC secretome in wound healing and skin rejuvenation.

FIGURE 1

Components of the UCMSC secretome. In all figures, a square with rounded corners stands for the component. The location of squares stands for the affiliation of different components. The UCMSC secretome is the collection of all proteins secreted by UCMSCs, which is generally regarded as UCMSC‐CM. UCMSC‐EV is a kind of tiny lipid membrane vesicle in UCMSC‐CM. UCMSC‐EVs can be divided into three subtypes: exosomes, MVs, and apoptotic bodies, with different diameters, respectively, 30–150 nm, 100–1000 nm, and 50–5000 nm.

FIGURE 2

The effects and mechanism of UCMSC secretome during the haemostasis stage. In all figures, the brown colour stands for the CM effect. UCMSC‐CM during the haemostasis stage mainly regulates the balance of the coagulation and anticoagulation systems. It can lead to wound healing mobilisation to enhance the amount of PDGF and platelets.

FIGURE 3

The effects and mechanism of UCMSC secretome during the inflammation stage. (Abbr. SP, signalling pathway) In all figures, the red, blue, and purple colours, respectively, stand for exosomes, EVs, and MVs effects. In all figures, black spots and dashed underlines stand for the fact that the substance only affects or is affected by the guided texts, not the whole cell. During the inflammation stage, the UCMSC secretome can affect inflammatory cell secretion, which causes a reduction of inflammatory factors, an enhancement of anti‐inflammatory factors, and a weakening of antigen presentation. It can also decrease T cell and leukocyte numbers and proliferation and regulate macrophage, monocyte, and dendritic cell activation and differentiation. Besides, the migration of keratinocytes is promoted.

FIGURE 4

The effects and mechanism of UCMSC secretome during the proliferation stage. ①Vascular endothelial cell: Angiogenesis is the greatest effect of the UCMSC secretome at this stage. Not only can it promote vascular endothelial cell migration and proliferation, but other skin cells are also activated to secrete VEGF and promote angiogenesis. ②Fibroblast and keratinocyte: Their migration and proliferation are enhanced to promote collagen synthesis, ECM deposition, and re‐epithelialization. ③Macrophage: The phenotype of macrophages changes from M1 to M2. The UCMSC secretome can reduce inflammation‐related gene and protein expression.

FIGURE 5

The effects and mechanism of UCMSC secretome during the remodelling stage. UCMSC‐exo can lessen the differentiation from fibroblast to myofibroblast and the cytoactive of fibroblasts and myofibroblasts, during the remodelling stage, mainly via the TGF‐β/Smad signalling pathway.