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. 2016 Nov;14(8):914–934. doi: 10.2174/1570159X14666160121115210

Table 1. Examples for the protective effects of MSCs in animal colitis models.

Animal Colitis Model Type of Stem Cells Amount, Route and Time of Appl. In Vivo Effects Refs.
Sprague-Dawley rat TNBS rat BMSC 1 x 107 topically (submucosal injection) and i.v., immediately after TNBS - i.v. no effect, accumulation in lungs
- topically protection, acceleration of healing, expression of VEGF and TGF-β1
Hayashi
et al., 2008 [230]
Lewis rat DSS rat BMSC 2 x 104/g i.v. on day 2 - no effect on inductive phase, modest promotion of recovery
- most growth factors and cytokines remained unchanged, but TGFα was increased and Notch signaling was inhibited
Tanaka
et al., 2011 [272]
C57BL/6J mouse DSS human BMSC and GMSC 2 x 106 i.p., on day 2 - amelioration of colitis, suppression of CD4+ T lymphocyte infiltration, reduction of pro-inflammatory cytokines IFN-γ, IL-6 and IL-17, elevation of IL-10 Zhang
et al., 2009 [156]
Balb/c mouse TNBS human and mouse ASC 1x105 – 106 i.p., 12 h after TNBS (hASCs and mASCs) and 106 i.p., 6 and 7 days after TNBS (hASCs) - inhibition of colitis development, partial reversal of already established colitis, decreased MPO activity, reduction of pro-inflammatory cytokines (TNF-α, IFN- γ, IL-6, IL-1β, IL-12) and chemokines (RANTES and macrophage
inhibitory protein 2), elevation of IL-10
Gonzalez
et al., 2009 [152]
C57BL/6 mouse DSS human and mouse ASC 1x105 – 5x106 i.p, on day 2, or in the case of cyclic DSS administration on day 7 of each cycle - amelioration of colitis, decreased MPO activity, reduction of pro-inflammatory cytokines (TNF-α, IFN- γ, IL-6, IL-1β,
IL-12) and chemokines (RANTES and macrophage
inhibitory protein 2), elevation of IL-10
Gonzalez-Rey et al., 2009 [153]
C57BL/6J Ico mouse
Balb/c mouse
DSS
TNBS
untreated and IFN- γ-prestimulated human and mouse BMSC 0.5x106 i.p, on day 0
1x106 i.p, 6 h after TNBS
- IFN- γ-prestimulated cells, but not untreated cells induced protection, decreased serum amyloid A levels, reduced
TNF-α, IL-6 and IL-17A, increased the level of IL-10
Duijvestein et al., 2011 [268]
Balb/c mouse DSS mouse BMSC 1x106 i.v, on days 2, 5 and 8 - alleviation of colitis, reduction of pro-inflammatory cytokines TNF-α and IL-1β He et al., 2012 [270]
C57BL/6J mouse DSS rat DPSC 1x105/10g i.v, on day 3 - protection from colitis via Fas ligand-induced T cell apoptosis Zhao et al., 2012 [251]
Wistar rat TNBS rat ASC and BMSC 2x106 i.p., 4 days after TNBS - i.p., but not i.v. injected stem cells migrated to the inflamed colon
- alleviation of colitis, reduction of epithelial apoptosis and pro-inflammatory cytokine production (TNF-α, IL-1β), elevation of IL-10
Castelo-Branco
et al., 2012 [278]
Balb/c mouse
C57BL/6 mouse
TNBS
DSS
mouse ASC and ASC-induced regulatory macrophages 1x106 i.p, immediately after TNBS, or in the case of chronic colitis on days 8 and 16
1x106 i.p, on day 2, or in the case of chronic colitis on days 4 and 14
- inhibition of colitis development and progression, decreased MPO activity, reduction of pro-inflammatory cytokines
(TNF-α, IL-6, IL-1β) and chemokines (RANTES)
Anderson et al., 2013 [279]
C57BL/6 mouse DSS mouse ASC 1x106 i.v or i.p., on days 2 and 5 - i.p. no effect
- amelioration of colitis only in the case of i.v. administration
Goncalves et al., 2014 [269]
Balb/c mouse DSS mouse BMSC 2.5x106 i.v, on day 7 - accelerated recovery, improved epithelial barrier
function via restoration of E-cadherin expression,
reduction of oxidative stress
Sun et al., 2015 [280]
C57BL/6 mouse DSS untreated and IFN- γ-overexpressed human UCSC 1x106 i.v., on day 2 - IFN- γ-overexpressed stem cells ameliorated colitis, reduced the number of Th1/Th17 cells and increased that of Treg/Th2 cells, decreased TNF-α, IL-6 and IL-1β, upregulated indoleamine 2, 3-dioxygenase expression Chen et al., 2015 [281]

Abbreviations for MSCs by origin: BMSC – bone marrow-derived mesenchymal stem cell, GMSC – gingival mesenchymal stem cell, ASC – adipose tissue-derived mesenchymal stem cell, DPSC – dental pulp mesenchymal stem cell, UCSC – umbilical cord-derived stem cell.