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.