Fractional carbon dioxide laser preconditioning potentiates adipose-derived mesenchymal stem cell exosomes for diabetic wound repair

Table 1 Cell-free mesenchymal stem cell therapies for skin wound healing

Cell-free therapies	MSC types	Models	Function	Ref.
MSC-Exos	Adipose-derived MSCs	SD rats: Full-thickness excision wound	Promote regular collagen deposition, angiogenesis, and hair follicle mosaicism regeneration	[14]
MSC-Exos	HUC-MSCs	C57BL/6 mice: Full-thickness excision wound	Promote wound healing by enhancing angiogenesis and inhibiting endothelial cell ferroptosis	[22]
MSC-Exos	UCB-MSCs	SD rats: Full-thickness excision wound	UCB-MSC-Exos accelerate wound closure, reduced scar formation, improved the regeneration of skin appendages, nerves, and vessels	[23]
MSC-Exos	HUCMSCs	Female SD rats: A skin burn model	HUC-MSC-Exo-treated wounds accelerated re-epithelialization	[24]
MSC-Exos	hBM-MSC-Exos	Female SD rats: Full-thickness excision wound	hBM-MSC-Exos promote the wound healing by inhibiting the transforming growth factor-β/SMAD signaling pathway	[16]
MSC-Exos	FDMSCs	BALB/c mice: Full-thickness excision wound	FDMSC Exos promote wound healing by enhancing the adult dermal fibroblast cell motility and secretion ability through Notch signaling pathway	[17]
MSC-Exos	DMSCs	129/SvJ mice: Full-thickness excision wound	DMSC-Exos can promote skin wound healing	[18]
MSC-EVs	WJ-MSCs	SD rats: Full-thickness excision wound	Accelerate wound closure, improve epidermal maturation, dermal regeneration, and reduce scarring	[25]
MSC-apoSEVs	Adipose-derived mesenchymal/stromal cells	Db/db diabetic mice: Full-thickness excision wound	ApoSEVs facilitate macrophages polarization from M1 to M2, enhance endothelial cell proliferation, migration, and tube formation, and stimulate fibroblast proliferation and migration	[26]
MSC-ABs	BMSCs	C57BL/6 mice: Full-thickness excision wound	Drive M0 macrophages to differentiate into M2 macrophages, regulating inflammation and angiogenesis to promote wound healing	[19]
MSC-ABs	BM-MSCs	Female C57BL/6 mice: Full-thickness excision wound	Promotes skin wound healing by polarizing macrophages to the M2 phenotype and enhancing fibroblast migration and proliferation	[27]
CM	HDP-MSCs	Human keratinocyte	HDP-MSC-derived secretome accelerates skin regeneration and modulates inflammatory responses	[20]
MSC-CM	HWJSC-CM	Female severe combined immunodeficiency and db/db diabetic model mice: Full-thickness excision wound	HWJSC-CM enhances healing of excisional and diabetic wounds by inducing keratinocyte differentiation and releasing key molecules	[28]

Exos: Exosomes; MSC: Mesenchymal stem cell; SD: Sprague-Dawley; HUC-MSCs: Human umbilical cord-derived mesenchymal stem cell; hBM-MSC-Exos: Human bone marrow-mesenchymal stem cell-derived exosomes; UCB-MSCs: Umbilical cord blood-derived mesenchymal stem cell; FDMSCs: Fetal dermal mesenchymal stem cell; DMSCs: Dermal mesenchymal stem cell; WJ-MSCs: Wharton’s Jelly-derived mesenchymal stem cell; BMSCs: Bone marrow-derived stem cells; CM: Conditioned medium; HDP-MSCs: Human dental pulp mesenchymal stem cell; EVs: Extracellular vesicles; apoSEVs: Apoptotic small extracellular vesicles; MSC-Abs: Mesenchymal stem cell-derived apoptotic bodies; HWJSC-CM Human umbilical cord Wharton’s jelly stem cells-conditioned medium.

Table 2 Mesenchymal stem cell preconditioning strategies for skin wound healing

Preconditioning strategies	MSC types	Derivatives	Models	Functions	Ref.
Qr preconditioning	HUC-MSCs	Exos: MSCs-Qr-Exos	SD diabetic rats: Full-thickness excision wound	MSC-Qr-Exos enhance fibroblast proliferation and migration, enhancing the therapeutic efficacy of MSC-Exos	[38]
RAPA preconditioning	HUC-MSCs	sEVs: RAPA-sEVs	C57/BL6 diabetic mice: Full-thickness excision wound	RAPA-sEVs effectively accelerate wound repair by promoting angiogenesis, reducing M1-type macrophages, and suppressing excessive inflammation with high biosafety	[15]
Curcumin preconditioning	BMSCs	Cur-Exos	SD diabetic rats: Full-thickness excision wound	Cur-Exos reduce wound size and promote epithelial migration and collagen deposition	[39]
PGZ preconditioning	Rat BMSCs	PGZ-Exos	SD diabetic rats: Full-thickness excision wound	PGZ-Exos enhance collagen deposition, ECM remodeling, and VEGF and CD31 expression, supporting angiogenesis in diabetic wound healing	[35]
Empagliflozin	Ad-MSCs	EMPA-Exos	db/db mice: Full-thickness excision wound	EMPA-Exos promote angiogenesis and accelerate diabetic wound healing by activating the PTEN/AKT/VEGF pathway	[36]
Hypo preconditioning	HUC-MSCs	Hypo-sEVs	db/db diabetic mice: Full-thickness excision wound	Hypo-sEVs promote diabetic wound healing and reduce excessive neutrophil extracellular trap formation by delivering miR-17-5p	[40]
Flavonoid preconditioning	Human umbilical cord WJ-MSCs	Fla-EVs	C57/BL6 mice: Full-thickness excision wound	Fla-EVs show strong anti-inflammatory and wound-healing effects in vitro and in vivo	[41]
Atorvastatin-preconditioning	hBM-MSCs	ATV-Exos	SD rats: Full-thickness excision wound	ATV-Exos facilitate wound regeneration by promoting blood vessel formation	[37]
Blue (455 nm) light illumination	HUC-MSCs	Blue light-treated MSC-Exos	Male C57BL/6 mice: A skin burn model	MSC-Exos promote in vivo angiogenesis, with enhanced proangiogenic effects under blue light irradiation	[42]
Serum- and glucose-deprived preconditioning	HUC-MSCs	SGD-EVs	Male SD rats: Full-thickness excision wound	SGD-EVs promote faster skin healing and angiogenesis in wound treatment	[43]

Qr: Quercetin; SD: Sprague-Dawley; HUC-MSCs: Human umbilical cord-derived mesenchymal stem cell; Exos: Exosomes; MSC: Mesenchymal stem cell; RAPA: Rapamycin; sEVs: Small extracellular vesicles; BMSCs: Bone marrow stromal cells; Cur-Exos: Curcumin-preconditioned stem cell-derived exosomes; PGZ: Pioglitazone; PGZ-Exos: Exosomes derived from mesenchymal stem cell pretreated with pioglitazone; Ad-MSCs: Adipose-derived-mesenchymal stem cell; EMPA-Exos: EMPA-pretreated mesenchymal stem cell-derived exosomes; Hypo: Hypoxic; Hypo-sEVs: Hypoxic pretreated mesenchymal stem cell-derived small extracellular vesicles; WJ-MSCs: Wharton’s Jelly-derived mesenchymal stem cell; Fla-EVs: Extracellular vesicles produced by mesenchymal stem cell treated with flavonoids; hBM-MSC: Human bone marrow-mesenchymal stem cell; ATV-Exos: Exosomes derived from atorvastatin-treated bone marrow stromal cells; SGD-EVs: Extracellular vesicles from serum- and glucose-deprived human umbilical cord-derived mesenchymal stem cell.