Table 1.

Sources of exosomes or exosome-like nanovesicles modulating macrophages toward IBD repair

Exosomes/exosome-like nanovesicles source	Condition	Mechanism	Reference
Stem/stromal cell
Hypoxia-prime adipose-derived stem cells	DSS-induced colitis	Control the HMGB1/TLR4/NF-κB signaling pathway to cause macrophage M2 polarization.	[97]
Human umbilical cord MSCs	DSS-induced colitis	Prevent macrophage pyroptosis brought on by casp4 in an inflammatory setting.	[31]
Human bone marrow-derived MSCs	DSS/TNBS induced colitis	Reduce inflammatory reactions, protects intestinal barrier integrity, polarizes M2b macrophages, and stimulates the production of IL-10. Primarily affects colonic macrophages.	[101]
Human umbilical cord MSCs	DSS-induced colitis	Enhance the expression of the IL-10 gene and decreases the infiltration of macrophages, TNF-α, IL-1β, IL-6, iNOS, and IL-7 genes.	[96]
Human umbilical cord MSCs	DSS-induced colitis	Suppress the release of IL-1β from mouse peritoneal macrophages and considerably lowers the relative expression of NLRP3, ASC, caspase-1, IL-18, and IL-1β in macrophages.	[29]
LbL-MSCs	UC	Increase M2 macrophages to control inflammation while decreasing M1 macrophages.	[98]
Human menstrual blood	DSS-induced colitis	Reduce colonic inflammation and polarize M2 macrophages in the colon.	[99]
Bone marrow MSC	DSS-induced UC	Encourage the polarization of M2-like macrophages, which is indicated by a rise in the M2 marker CD163. Upregulate TGF-β and IL-10 and downregulate TNF-α, CCL-24, TNF-α, VEGF-A, and IFN-γ levels.	[100]
Macrophage
M2	DSS-induced colitis	MiR-590-3p, highly concentrated in M2 exosomes, suppresses the production of proinflammatory cytokines such as IL-1β, IL-6, and tumor necrosis factor-α.	[49]
M2	DSS-induced colitis	Inhibit IL-1β, IL-6, and IL-17A. Offer protection against colitis produced by DSS, mostly through the CC chemokine 1 (CCL1)/CCR8 axis.	[11]
Food
Turmeric	Colitis	It increase the M1 phenotype’s transition to M2 macrophages and restores the impaired gut epithelial barrier.	[112]
Ginseng	DSS-induced colitis	Stimulate the synthesis of anti-inflammatory macrophages while downregulating proinflammatory cytokines in proinflammatory macrophages.	[113]
Spermidine	DSS-induced colitis	Increase the markers for M2 macrophages while decreasing the markers for M1 macrophages in the inflammatory colons.	[115]
Colostrum	DSS-induced UC	Stimulate the growth of macrophages and colonic epithelial cells, reduce inflammation by efficiently eliminating ROS, and control the release of immune cytokines.	[50]
Milk	DSS-induced UC	Reduce the inflammatory response by blocking the activation of the NLRP3 inflammasome and the TLR4-NF-κB signaling pathway. Stop the release of cytokines and macrophage polarization toward a proinflammatory phenotype.	[116]
Other exosomes/EVs
Trichinella spiralis	DSS-induced colitis	Activate M2 macrophages in the colon and prevent M1 macrophage polarization.	[117]
HEK293T cells	Sepsis-induced intestinal damage	Minimize systemic inflammation and mortality while promoting M2 polarization by reducing mitochondrial reactive oxygen species (mtROS).	[118]
Other immune cells
G-MDSC	DSS-induced colitis	The G-MDSC exosome (containing Arg-1) inhibits the delayed-type hypersensitivity response, reduces the growth of CD4+ T cells, and decreases IFN-γ and TNF-α levels.	[110]

Abbreviations: ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain; DSS, dextran sulfate sodium; G, granulocytic; HMGB1, high mobility group box 1; IFN-γ, interferon-gamma; IL, interleukin; ILVs, intraluminal vesicles; iNOS, inducible nitric oxide synthase; M, macrophage; MDSC, myeloid-derived suppressor cells; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NLRP3, NOD-like receptor family, pyrin domain-containing 3; ROS, reactive oxygen species; TGF-β, transforming growth factor beta; TLR4, Toll-like receptor 4; TNBS, 2,4,6-trinitrobenzenesulfonic acid solution; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.