Insights into optimizing exosome therapies for acute skin wound healing and other tissue repair

doi:10.1007/s11684-023-1031-9

Front. Med.

2024, Vol. 18

Issue (2) : 258-284 https://doi.org/10.1007/s11684-023-1031-9

Insights into optimizing exosome therapies for acute skin wound healing and other tissue repair

Tianjing Sun¹, Mo Li¹, Qi Liu²(

), Anyong Yu¹(

), Kun Cheng³, Jianxing Ma⁴, Sean Murphy⁵, Patrick Michael McNutt⁵, Yuanyuan Zhang⁵(

)

¹. Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China
². Department of Nephrology, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, China
³. Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA
⁴. Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
⁵. Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27109, USA

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Abstract

Exosome therapy holds great promise as a novel approach to improve acute skin wound healing. This review provides a comprehensive overview of the current understanding of exosome biology and its potential applications in acute skin wound healing and beyond. Exosomes, small extracellular vesicles secreted by various stem cells, have emerged as potent mediators of intercellular communication and tissue repair. One advantage of exosome therapy is its ability to avoid potential risks associated with stem cell therapy, such as immune rejection or stem cells differentiating into unwanted cell types. However, further research is necessary to optimize exosome therapy, not only in the areas of exosome isolation, characterization, and engineering, but also in determining the optimal dose, timing, administration, and frequency of exosome therapy. Thus, optimization of exosome therapy is critical for the development of more effective and safer exosome-based therapies for acute skin wound healing and other diseases induced by cancer, ischemia, or inflammation. This review provides valuable insights into the potential of exosome therapy and highlights the need for further research to optimize exosome therapy for clinical use.

Keywords exosomes stem cells therapeutic impact skin wound healing

Corresponding Author(s): Qi Liu,Anyong Yu,Yuanyuan Zhang

Just Accepted Date: 23 October 2023 Online First Date: 12 January 2024 Issue Date: 27 May 2024

Cite this article:

Tianjing Sun,Mo Li,Qi Liu, et al. Insights into optimizing exosome therapies for acute skin wound healing and other tissue repair[J]. Front. Med., 2024, 18(2): 258-284.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-023-1031-9
https://academic.hep.com.cn/fmd/EN/Y2024/V18/I2/258

Fig.1 Pathophysiological changes at different stages of skin wound healing. (A) At the hemostasis stage, platelets are activated and release various cytokines and growth factors, recruit immune cells and induce vasoconstriction. (B) In the stage of inflammatory response, macrophages and neutrophils gather at the site of injury, macrophages release inflammatory factors, and the M1 phenotype transitions to M2 phenotype to promote wound healing. (C) Endothelial cell vascularization and fibronectin migration promote collagen formation during the proliferation stage. (D) The main process during the remodeling stage involves the formation of type I and II collagen, as well as the reorganization of collagen and ECM. ECM, extracellular matrix.

Fig.2 The mechanism of exosomes therapy for acute skin wound. (A) Exosomes of different cellular origins, such as fibroblast, macrophage, stem cell and platelet etc. (B) The role of exosomes in wound healing of the skin includes alleviating inflammatory reactions, promoting proliferation and migration of fibroblasts, promoting angiogenesis of endothelial cells, and accelerating remodeling of extracellular matrix and collagen. (C) Exosomes accelerate skin wound healing and reduce scar formation.

Tab.1 Comparison of stem cell therapy and exosome therapy

Tab.2 Optimization of the yield and quality of exosomes as well as exosome therapy

Fig.3 Optimization of exosomes yield and therapy for skin acute wound healing, including optimization of exosome sources, culture conditions, storage conditions, isolation, genetic engineering and optimal does, timing, frequency, administration routine of exosomes.

Tab.3 Exosome isolation techniques and their comparison

Fig.4 Engineered exosomes for skin wound healing, including surface and genetic engineering, precondition and loaded.

Tab.4 Engineered exosomes better improve skin wound healing

Tab.5 Comparison of exosome administration

Indication	Diseases	Exosome source	Effective molecules	Outcomes	References
Cancer	Glioma	Neutrophils	–	Loaded with doxorubicin, inhibit glioma progression via BBB transfer to the TME	[162]
	Colorectal cancer	293T cells	miR-21↓, PTEN and hMSH2↑	Decrease tumor proliferation and increase apoptosis to inhibit tumor growth	[164]
	Gastric cancer	HEK293T cells culture media and plasma	miR-214↓	Induce cell apoptosis, reduce proliferation and migration, and increase drug sensitivity	[165]
	BC	Breast tumor cells	miRNA-16-5p↓, CD73↑	BC-derived exosome SNHG16/miR-16-5p/SMAD5-regulatory axis potentiates TGF-β1/SMAD5 pathway activation, to induce CD73 expression in Vδ1 T cells	[168]
	BC	CAF	miR-92, PD-L1↑	Promotes apoptosis and impaired proliferation of T cells	[169]
Ischemia-induced injury or diseases	MI	hUSC	Cx43, Ki67, CD31, α-SMA, Vwf, TGF-β1, MMP-9, etc.↑	Promote cell proliferation and angiogenesis, enhancing ejection fraction	[171]
	IS	IPAS	circSHOC2, miR-7670-3p, SIRT1↑	Regulate autophagy and reduce neuronal apoptosis	[172]
	IS	Lactobacillus plantarum	miR-101a-3p↑	Inhibit neuron apoptosis to protect against ischemic brain injury through the microRNA-101a-3p/c-Fos/TGF-β axis	[173]
	Kidney I/R	HUVEC	NF-κb activity↓	Decreased NF-κB activity, expression of pro-inflammatory cytokines and adhesion molecules	[174]
Inflammatory-related diseases	Atherosclerosis	HEK293T cells	miR-155 ↑	Exosome-based delivery of the engineered IL-10 could alleviate the atherosclerosis in ApoE mice	[180]
	AA	M2 macrophage	Inflammatory cytokines↓	Ameliorated AA with a marked reduction of lung inflammation	[181]
	TBI	Astrocyte	miR-873a-5p↑	Inhibited LPS-induced microglial M1 phenotype transformation and inflammation through decreased phosphorylation of ERK and NF-κB p65	[182]
	Murine colitis	M2 macrophage	miR-590-3p, LATS1↑	Reduces inflammatory signals and promotes epithelial regeneration	[183]
	NASH	HLSCs	α-SMA, Col1a, Tgf-β1, TNF, IL-1β↓	Display anti-fibrotic and anti-inflammatory effects to improve liver function	[186]
	EAE	HUCB	IL-2, MMP-9, HSP-72↑	Inhibited T cell proliferation and EAE development by regulating IL-2 signaling	[189]

Tab.6 Exosome therapy used in other diseases

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