Advances in biological functions and applications of apoptotic vesicles

Zou, Xianghui; Lei, Qian; Luo, Xinghong; Yin, Jingyao; chen, Shuoling; Hao, Chunbo; Shiyu, Liu; Ma, Dandan

doi:10.1186/s12964-023-01251-9

Cell Communication and Signaling

Table 1 Direct therapeutic applications of apoptotic vesicles

From: Advances in biological functions and applications of apoptotic vesicles

Published year	Term	Parental cell	Size of vesicles	Induction method	Isolation method	Function	Target cell	Animal	Applied method	Disease model	Ref.
2022	Apoptotic vesicles	RAW264.7 macrophages	240.6±115nm	STS and serum-free	Sequential centrifugation	Inhibit osteogenesis and promot adipogenesis of MSCs	Human ADSCs	Nude mice	Implant with collagen sponges or β-TCP	N/A	[74]
2022	Apoptotic vesicles	Human BMMSCs	150.1±14.8nm	STS	Sequential centrifugation	Switch neutrophils NETosis to apoptosis, ameliorate multiple organ dysfunction and improve survival in septic mice	Bone marrow neutrophils	Mice	Inject intravenously	Sepsis	[68]
2022	Apoptotic vesicles	Murine BMMSCs	Approximately 50-1000nm	Serum-free and STS, or DCPy with ultralow-power light irradiation	Sequential centrifugation followed by sequential filtering analysis	Promote wound healing and hair growth via activation of Wnt/β-catenin pathway	Skin and hair follicle MSCs	Mice	Inject subcutaneously or intravenously	SLE	[69]
2022	Apoptotic vesicles	Human DPSCs	Around 100-800nm	STS	Sequential centrifugation	Transport TUFM to activate ECs autophagy and promote ECs angiogenesis via the TFEB-induced autophagy-lysosome pathway	ECs	Nude mice, beagle dogs	Implant tooth scaffolds filled with ApoEVs subcutaneously in the dorsum(mice), inject ApoEVs gel material into the root canal of the anterior tooth after removal of the pulp(dogs)	N/A	[24]
2022	Apoptotic vesicles	Human ESCs and iPSCs	Approximately 50-200nm	STS and serum-free	Sequential centrifugation	Promote mouse skin wound healing via transferring SOX2 into skin MSCs to activate Hippo signaling pathway	Skin MSCs	Mice	Inject intravenously	Skin wound	[62]
2022	Apoptotic bodies	Mouse ADSCs	800-1600nm	STS, desacetylcinobufotalin, hydroxyurea, or hypocrellin B	Sequential centrifugation	Induce M2 polarization of macrophages	Macrophages	Mice	Inject subcutaneously	Skin wound	[61]
2021	Apoptotic extracellular vesicles	Mouse T cells	200-2000nm	T cell-depleting nanoparticles with Fas-ligand	Sequential centrifugation	Promote macrophages transformation towards the M2 phenotype	Macrophages, BMMSCs	Mice	Induce ApoEVs production in vivo	Osteoporosis	[73]
2021	Apoptotic bodies	Human UCMSCs	200-3000nm	UVC light	Sequential centrifugation	Induce macrophages immunomodulation, cell proliferation, and angiogenesis	Macrophages, human endometrial stromal cells, ECs	Mice, rats	Load into a hyaluronic acid hydrogel and inject in situ	Acute endometrial damage (mice), intrauterine adhesions (rat)	[67]
2021	Apoptotic bodies	Rat bone marrow neutrophils	800-1200nm (Neu-ABs), 100-400nm (eNABs)	STS	Sequential centrifugation	Inflammation-tropism and immunoregulatory effects	Macrophages	Rats	Inject intravenously	Myocardial infarction	[72]
2021	Apoptotic vesicles	Human BMMSCs	<700nm	STS	Sequential centrifugation	Alleviate macrophages infiltration and promote macrophages polarization towards M2 phenotype	Macrophages	mice	Inject intravenously	Type 2 diabetes	[25]
2021	Apoptotic extracellular vesicles	Mouse BMMSCs	Around 50-250nm	STS and serum-free	Sequential centrifugation	Facilitate Fas trafficking from the cytoplasm to the cell membrane of tumor cells by evoking Ca2+ influx and elevating cytosolic Ca2+, use Fas ligand to activate the Fas-FasL pathway	Multiple myeloma cells	Mice	Inject intravenously	Multiple myeloma	[70]
2021	Apoptotic bodies	Mouse pOCs and mOCs	Unknown	STS	Sequential centrifugation	pOC-ABs induce EPCs differentiation and increase ECs formation, mOC-ABs induce osteogenic differentiation of MSCs and facilitate osteogenesis	EPCs, MSCs	Mice	Graft decalcified bone matrix pre-incubated with different ApoBDs in the defect area	Bone defect	[75]
2020	Apoptotic bodies	Murine BMMSCs	Approximately 600-1600nm	STS	Sequential centrifugation	Trigger the polarization of macrophages towards M2 phenotype	Macrophages (macrophages further enhance the migration and proliferation abilities of fibroblasts)	Mice	Locally administrate in skin wound	Skin wound	[23]
2020	Apoptotic bodies	Mouse T cells	700-2000nm (ABs), 100-600nm (cABs)	STS	Sequential centrifugation	Target inflammatory regions and modulate inflammatory processes	Macrophages	Mice	Inject intravenously	Cutaneous inflammatory wound, colitis	[15]
2020	Apoptotic bodies	Mouse pOCs and mOCs	Approximately 1-4μm	STS	Sequential centrifugation and sequential filtering	pOC-ABs induce angiogenesis, mOC-ABs promote osteogenesis	EPCs, MC3T3-E1	Mice	Graft decalcified bone matrix pre-incubated with different ApoBDs in the defect area	Bone defect	[29]
2020	Apoptotic bodies	Mouse and rat BMMSCs	400-700nm	STS	Sequential centrifugation	Enhance angiogenesis of ECs and improve cardiac functional recovery	ECs	Rats	Inject intramyocardially	Myocardial infarction	[63]
2019	Apoptotic extracellular vesicles	Mouse thymocytes, Jurkat cells	50-100nm	Gamma ray or UV irradiation	Sequential centrifugation	Promote TGFβ production in macrophages	Macrophages	Mice	Inject intraperitoneally	Colitis	[36]
2019	Apoptotic bodies	mOCs	Approximately 1-4μm	Nitrogen-containing bisphosphonate alendronate	Sequential centrifugation and sequential filtration	Promote osteogenic differentiation	MC3T3-E1	N/A	N/A	N/A	[76]
2018	Apoptotic bodies	BMMSCs	1-5μm	STS	Sequential centrifugation followed by sequential filtering	Maintain MSCs homeostasis and ameliorate osteopenia	BMMSCs	Mice	Inject intravenously	Osteopenia	[66]
2009	Apoptotic bodies	Vascular ECs	Unknown	Serum and growth factors-free	Sequential centrifugation	Convey paracrine alarm signals to recipient vascular cells that trigger the production of CXCL12	Vascular ECs	Mice	Inject intravenously	Atherosclerosis	[77]

Abbreviations: STS Staurosporine, MSCs Mesenchymal stem cells, ADSCs Adipose-derived stem cells, β-TCP β-tricalcium phosphate, BMMSCs Bone marrow mesenchymal stem cells, SLE Systemic lupus erythematosus, DPSC Dental pulp stem cells, TUFM Mitochondrial Tu translation elongation factor, ECs Endothelial cells, TFEB Transcription factor EB, ESCs Embryonic stem cells, iPSCs induced pluripotent stem cells, UCMSCs Umbilical cord-derived mesenchymal stem cells, UV Ultraviolet, Neu-ABs Apoptotic bodies from neutrophils, eNABs engineered neutrophil apoptotic bodies, pOCs Preosteoclasts, mOCs mature osteoclasts, pOC-ABs preosteoclast apoptotic bodies, mOC-ABs mature osteoclast apoptotic bodies, EPCs Endothelial progenitor cells, ABs Apoptotic bodies, cABs chimeric apoptotic bodies

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ISSN: 1478-811X

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