Mesenchymal stem cell-derived exosomes: A novel and potential remedy for cutaneous wound healing and regeneration

Table 1 Preclinical studies of mesenchymal stem cell-exosomes in cutaneous wound healing phases

Wound healing phase	Exosome cellular origin	Model	Functional effects	Pathways	Ref.
Inflammation	hBMMSCs; hJMMSCs	Mice dorsal skin defects	Macrophage M2 polarization	miR-223 via pknox1	[38]
	hUCMSCs	Rat severe burn	M2 polarization. Inflammation alleviation	miR-181c via TLR4	[39]
	LPS-pretreated hUCMSCs	Rat diabetic cutaneous wound	M2 polarization	Let-7b via TLR4/NF-κB/STAT3/AKT	[40]
	mBMMSCs	Mice skin excision wound	Promote beneficial regulatory T cell responses and M2 polarization	M2/Th2/Treg responses	[44]
Proliferation	hADMSCs	Mice full-thickness incision wound	Promote fibroblast proliferation and migration; optimize collagen deposition	PI3K/Akt	[47]
	hUCMSCs	Rat skin burn	Enhance re-epithelialization and cell proliferation; reduce heat stress-induced apoptosis	Wnt/β-catenin; AKT	[51]
	hiPSC-MSCs	Rat dorsal skin wound	Accelerate skin cell proliferation and migration; promote collagen synthesis and angiogenesis	ERK1/2	[52,53]
Remodeling	hADMSCs	Mice skin incisional wound	Mitigating scar formation; promote ECM reconstruction	ERK/MAPK	[55]
	hUCMSCs	Mice full-thickness skin defects	Suppress myofibroblast differentiation and scar formation	TGF-β/SMAD2	[56,57]
	hAFSCs	Rat full-thickness skin wound	Anti-fibrotic scarring; suppress the excessive aggregation of myofibroblasts and ECM	TGF-β	[58]

BMMSCs: Bone marrow MSCs; ECM: Extracellular matrix; hADMSCs: Human adipose-derived MSCs; hAFSCs: Human amniotic fluid stem cells; hBMMSCs: Human BMMSCs; hiPSC-MSCs: Human induced pluripotent stem cell-derived MSCs; hJMMSCs: Human jaw bone marrow MSCs; hUCMSCs: Human umbilical cord MSCs; LPS: Lipopolysaccharide; mBMMSCs: Mice BMMSCs; MSCs: Mesenchymal stem cells; TGF-β1: Transforming growth factor-β1; TLR4: Toll-like receptor 4.