TABLE 3.

MSC-sEVs play an active role in regulating inflammatory cells.

MSC source	Isolation	Target cells/conditions	Functional cargo	Molecules/Pathways affected	Key functions/Downstream genes	Reference
BM	precipitation	cutaneous wound in mice; human monocytes in vitro	miR-223	Pknox1↓	enhanced M2 polarization, TNF-α↓, IL-10↑, Arg-1↑	He et al. (2019)
Huc	Size-Exclusion Chromatography	T cell, PBMCs	—	—	reduced T cell proliferation	Monguió-Tortajada et al. (2017)
BM	Ultracentrifugation	PBMC, T and B cells	—	—	Decreased proliferation of PBMC, T and B cells and IgM levels	Khare et al. (2018)
Fetal liver	ultracentrifugation	NK cells	LAP, TGFβ and TSP1	p-SMAD2/3↓	Restrained proliferation, function and activity of NK cells	Fan et al. (2019)
LPS-pre-huc	ultracentrifugation	Diabetic cutaneous wound in rats; THP-1 in vitro	let-7b	TLR4↓, p-P65↓, NF-κB↓, p-STAT3↑, p-AKT↑	Skewed macrophage polarization to M2 and clearance of chronic inflammation	Ti et al. (2015)
Menstrual blood	Ultracentrifugation	cutaneous wound in diabetic mice	—	ARG/iNOS↑	Elevated M2/M1 ratio and resolved inflammation	Dalirfardouei et al. (2019)
Murine BM	ultracentrifugation	DFU model in mice; HDF	LncRNA H19	miR-152-3p↓ → PTEN↑ → p85PI3K↓→p-AKT↓→IL-1β↓, TNF-α↓, and IL-10↑	suppressed apoptosis and inflammation in vitro and in vivo	Li et al. (2020)
BM	Ultracentrifugation	EPC; cutaneous wound in diabetic rats	Nrf2	IL-1β↓, TNF-α↓and IL-10↑, IL-4↑	Reduced inflammation	Wang et al. (2021a)

Huc, human umbilical cord; BM, bone marrow; Pknox1, PBX/knotted 1 homeobox one; PBMCs, Peripheral Blood Mononuclear Cells; LAP, latency associated peptide; TGFβ, transforming growth factor β; TSP1, thrombospondin 1; ARG, arginase; THP-1, human myeloid leukemia mononuclear cells; TLR4, Toll-like receptors 4; DFU, diabetic foot ulcer; AT, adipose tissue; Nrf2, nuclear factor erythroid 2–related factor 2; EPC, endothelial progenitor cell; SMP30, senescence marker protein 30; NOX1/4, NAPDH, oxidase 1/4; TNF-α, Tumor Necrosis Factor α; hAAM, human acellular amniotic membrane.