TABLE 2.

Effects of MSC-EVs in various tissue repair and regeneration relevant to oral and craniomaxillofacial regions.

	Stem cell type of MSC-EVs	Type of EVs	Target tissue	Biomolecules/Signaling pathways	Mechanism of treatment effect	References
1	MSC	EVs	Muscle	Ca2+, ERK 1/2	ERK1/2 in muscle tissue is necessary for calcium signaling, but not in the spinal cord	Levin and Borodinsky, (2022)
2	ADSC	EVs	Skin	ADSC-EVs, MMP-9	ADSC-EVs inhibit downregulating MMP-9 and improve collagen deposition	Wang et al. (2022)
3	ADSC	Exos	Nerve	ADSC-Exos	Enhance the expression and differentiation of PC12 cells into neurons	Shariati Najafabadi et al. (2021)
4	BMMSC	Exos	Vessel	Wnt3a	BMMSC-Exos transport Wnt3a exteriorly and enhance dermal fibroblast proliferation, migration, and angiogenesis in vitro	McBride et al. (2017)
5	BMMSC	Exos	Bone	Wnt/β-catenin signaling pathway, Exos	BMMSC-Exo loaded with Wnt can activate Wnt/β-Catenin signal transduction and alleviate bone loss caused by radiation	Zuo et al. (2019)
6	BMMSC	EVs	Bone	Cordycepin	Cordycepin promotes osteogenesis of BMMSCs and accelerates fracture healing via hypoxia	Li et al. (2020)
7	DPSC ADSC	EVs	Bone	ERK1/2, JNK, MAPK signaling pathway	When DPSC is co cultured with ADSC, the osteogenic ability is significantly enhanced. DPSC-EV can promote the osteogenic differentiation of ADSC through MAPK pathway by enhancing the phosphorylation of ERK1/2 and JNK	Jin et al. (2020)
8	MSC	Exos	Bone	miRNA	MSC-EVs pretreated with TNF-α can change miRNA composition, thereby controlling macrophage phenotype to control inflammatory balance and promote osteogenesis	Kang et al. (2022)
9	MSC	Exos	Bone	MAPK signaling pathway	MSC-Exo could promote the proliferation of hFOB 1.19 through MAPK signaling pathway, thus alleviating the progression of osteoporosis	Zhao et al. (2018)
10	BMMSC	EVs	Cartilage	TNF-α, COX-2, collagenase	BMMSC-EV can down regulate TNF-α mediated COX-2 and pro-inflammatory interleukin levels inhibit collagenase activity and promote cartilage regeneration	Vonk et al. (2018)
11	MSC	Exos	Cartilage	Akt/Bad/Bcl-2 signaling pathway	PRP-Exos have the capability to prevent GC-induced apoptosis in a rat model of ONFH by promoting Bcl-2 expression via the Akt/Bad/Bcl-2 signal pathway under ER stress	Tao et al. (2017a)
12	hUCMSC	Exos	Skin	Wnt4	hUCMSC-Exo contributes to skin wound healing by transmitting Wnt4	Zhang et al. (2015)
13	hUCMSC	Exos	Skin	TGF-β1/Smad 2/3 signaling pathway	hUCMSC-Exo suppress dermal fbroblasts-myofbroblats transition via inhibiting the TGF-β1/Smad 2/3 signaling pathway	Hu et al. (2020)
14	MSC	EVs	Skin	miR-29a-3p	MSC-EVs alleviate systemic sclerosis via miR-29a-3p	Rozier et al. (2021)
15	DPSC	Exos	Tooth	miRNAs, TGF-β1/smads signaling pathway	Lineage specific exosomes can transfer miRNA in TGFbeta1/smads signaling pathway to induce odontogenic differentiation of human dental pulp stem cells	Hu et al. (2019)
16	PDLSC	Exos	Periodontal	miRNA-155-5p, Th17 Treg	In chronic periodontitis, exosomal microRNA-155-5p in PDLSCs can be used to regulate sirtuin-1 to achieve Th17/Treg balance	Zheng et al. (2019)
17	DPSC	EVs	Periodontal	miRNA-378a, Hedgehog/Gli1 signaling pathway	Periodontitis-compromised DPSCs secrete EVs carrying miRNA-378a promote local angiogenesis by targeting Sufu to activate the Hedgehog/Gli1 signaling	Zhou et al. (2021)
18	SHED BMMSC	Exos	Periodontal	Runx2, p-Smad5	SHED-Exo directly promoted BMMSC osteogenesis, differentiation and bone formation	Wei et al. (2020)
19	BMMSC	Exos	Periodontal	Akt/ERK signaling pathway	MSC exosomes can increase PDL cell migration and proliferation through CD73 mediated adenosine receptor activation of survival promoting Akt and ERK signaling	Chew et al. (2019)

Note: Biomolecules/Signaling pathways refers to the biomolecules or signaling pathways through which MSC-EVs, work out in target tissue.