Skip to main content

Table 3 Functions and applications of exosomes in NEC

From: Stem cells and exosomes: promising candidates for necrotizing enterocolitis therapy

Exosome type Exosome origin Exosome isolation Exosome concentration Exosome administration Model Modeling methoda Main findings Mechanism Reference
AF-MSC-Ex Rat ExoQuick reagent / Intraperitoneal injection In vitro
In vivo
Ex vivo
Mouse pup with formula, exposure to hypoxia for 4 days and oral LPS injection (4 mg/kg for 2 days) AF-MSC-Exs increase cellular proliferation, reduce inflammation, and regenerate a normal epithelium.
AF-MSC-Exs attenuate NEC intestinal injury via activating the Wnt signaling pathway.
Wnt/β-catenin (ISCs) [28]
BM-MSC-Ex Mouse Serial centrifugation (in vitro)
PureExo Exosome Isolation kit (in vivo)
~ 2.5 ×109 exosomes/50 μL Intraperitoneal injection In vitro
In vivo
Mouse pup with formula, hypoxia (100% N2, 1.5 min, bid for 4 days) and hypothermia (4 °C, 10 min, bid for 4 days) BM-MSC-Exs increase wound healing in vitro.
BM-MSC-Exs significantly lower gut permeability and the incidence of NEC in vivo.
/ [43]
AF-MSC-Ex Rat Ultra-centrifugation 4 × 108 exosomes/50 μL Intraperitoneal injection In vivo Rat pups with formula, hypoxia (100% N2, 1.5 min, tid for 4 days) and hypothermia (4 °C, 10 min, tid for 4 days) BM-MSC-Exs, AF-MSC-Exs, amniotic fluid-derived NSC-Exs and enteric NSC-Exs demonstrate equivalent reductions in NEC incidence.
Stem cell-derived exosomes are equivalent to stem cells in NEC therapy.
/ [44]
BM-MSC-Ex
NSC-Ex (amniotic fluid-derived)
NSC-Ex (enteric)
HM-Ex Human Ultra-centrifugation 0–10 μg / In vitro / HM-Exs reduce oxidative stress-related injury on intestinal epithelial cells. / [45]
HM-Ex Human Serial centrifugation 0.1 μg/μL / Ex vivo / HM-Exs derived from colostrum, transitional or mature human milk prevent inflammatory injury.
HM-Exs derived from colostrum are most effective in decreasing inflammatory cytokine.
/ [46]
HM-Ex Human Ultra-centrifugation 200 μg/mL Gavage In vivo Rat pups with formula and hypoxia (5% O2, 75% N2, 5 min, bid for 4 days) HM-Exs promote the proliferation and migration of intestinal epithelial cells both in vitro and in vivo.
Peptidomic differences between preterm and term milk exosomes are revealed.
/ [47]
HM-Ex Human Ultra-centrifugation 0–1 × 108 exosomes/100 μL Intraperitoneal injection
Gavage
In vitro
In vivo
Rat pups with formula, hypoxia (< 1.5% O2, 1.5 min, tid for 4 days), hypothermia (4 °C, 10 min, tid for 4 days) and LPS (2 mg/kg, day 1) HM-Exs increase the proliferation and decrease the apoptosis of intestinal epithelial cells.
HM-Exs administered intraperitoneally or enterally decrease NEC incidence.
HM-Ex enteral administration has better effects.
/ [48]
HM-Ex Human Ultra-centrifugation 1.15–1.19 g/mL Gavage Ex vivo
In vivo
Mouse pups with formula, hypoxia (5% O2, 10 min, tid for 5 days) and LPS (4 mg/kg, qd for 5 days) HM-Exs reduce inflammation and improve mucus production in vivo.
HM-Exs decrease inflammation in hypoxia and LPS-treated intestinal organoids.
Pasteurized HM-Exs are as effective as raw HM-Exs.
/ [49]
HM-Ex Human ExoQuick reagent 0.5 mg/mL / In vitro / HM-Exs upregulate Wnt/β-catenin signaling in ISCs and increase cell viability under H2O2 exposure compared to the control group. Wnt/β-catenin (ISCs) [50]
PM-Ex Pig Ultra-centrifugation 0.037 mg/μL Gavage In vitro
In vivo
Mouse pups with LPS (7.5 mg/kg, qd for 7 days) PM-Exs inhibit intestinal epithelial cell apoptosis and decrease TLR4/NF-κB signaling through miRNAs in vitro.
PM-Exs prevent LPS-induced intestinal injury and inflammation in vivo.
miRNAs (miR-4334, -219, -338) [51]
BovM-Ex Cow Ultra-centrifugation 1 μg/μL Gavage In vitro
In vivo
Mouse pups with formula, hypoxia (5% O2, 10 min, tid for 5 days) and LPS (4 mg/kg, day 6 and 7) BovM-Exs promote goblet cell and endoplasmic reticulum chaperone protein expression both in vitro and in vivo, which increases mucus production and protect the intestine. TFF3, MUC2 (goblet cell), and GRP94 (endoplasmic reticulum) [52]
  1. aModeling methods for in vivo studies