Cell membrane and bioactive factors derived from mesenchymal stromal cells: Cell-free based therapy for inflammatory bowel diseases

Table 1 Studies using bioactive factors derived from mesenchymal stromal cells as a therapeutic strategy for inflammatory bowel diseases

Bioactive factors	MSC origin	IBD model	Pathway	Results	Ref.
CM	Rat bone-marrow	DSS and TNBS-induced colitis in rats	IP, IV, and enema	Effective for the inductive phase of TNBS-induced colitis and for recovery phase of DSS-induced colitis.	Watanabe et al[15], 2014
CM	Human bone-marrow	TNBS-induced colitis in pigs	Enema	Prevent loss of myenteric neurons and damage of nerve process.	Robinson et al[115], 2014
EVs	Rat bone-marrow	TNBS-induced colitis in rats	IV	Inhibit NF-κBp65 pathways, modulate anti-oxidant/oxidant balance, and apoptosis.	Yang et al[132], 2015
Exosomes	Human umbilical cord	DSS-induced colitis in mice	IV	Increase IL-10 and decrease TNF-α, IL-1β, IL-6, iNOS, and IL-17.	Mao et al[114], 2017
Extract	Human umbilical cord	DSS-induced colitis in mice	IP	Inhibit inflammatory cytokines and alter macrophage functional phenotype from M1 to M2	Song et al[107], 2017
CM	Mouse adipose tissue	DSS-induced colitis in mice	IP	Increase Treg, IL-10, and TGF-β, and decreased IL-17.	Heidari et al[116], 2018
CM	Mouse adipose tissue	DSS-induced colitis in mice	IP	Increase Treg, IL-10, and TGF-β, and decreased IL-17.	Pouya et al[117], 2018
CM	Human umbilical cord	DSS-induced colitis in mice	Culture medium (organ culture)	Decrease IL-6 and increase Ki-67.	DA Costa Gonçalves et al[119], 2018
Exosomes	Human umbilical cord	DSS-induced colitis in mice	IV	Downregulated ubiquitin inhibiting NF-κB and mTOR activation.	Wu et al[133], 2018
EVs	Mouse bone-marrow overexpressing miR-146a	TNBS-induced colitis in rats	IV	Suppress the activation of NF-kB pathway, decrease TNF-α, IL-6, and IL-1β.	Wu et al[131], 2019

MSC: Mesenchymal stromal cells; IBD: Inflammatory bowel diseases; DSS: Sodium dextran sulfate; CM: Conditioned medium; EVs: Extracellular vehicles; TNBS: Trinitrobenzene sulfonic acid; IP: Intraperitoneal; IV: Intravenous; TGF: transforming growth factor; Treg: Regulator T cell; NF-κB: Nuclear factor kappa B; IL, Interleukin; TNF-α: Tumor necrosis factor-alpha.