. 2019 Dec 10;17:412. doi: 10.1186/s12967-019-02167-0

Table 1.

The potential immunoregulatory mechanisms of MSCs in improving the prognosis of LT

Species of MSCs	Pretreatment	Source	Dose (number)	Model	Mechanism	Effect	Refs.
Mouse	N/A	Bone marrow	1 × 10⁶	Mouse	Suppress Kupffer cell apoptosis, Th1/Th17 immune responses, chemokine expression and inflammatory cell infiltration	Alleviate liver graft injury; upregulate the survival rate of animals with LT	[70]
Rat	N/A	Bone marrow	2.5 × 10⁵	Rat	Inhibit the proliferation of CD4+ T cells and activation of CD8+ T cells; upregulate the levels of TGF-β1, FoxP3, IL-10, and CTLA-4	Attenuate the rejection rate of LT	[71]
Human	N/A	Umbilical cord	1 × 10⁶/kg body weight	Human	Activate Tregs; inhibit Th17 cells; increase the expression levels of TGF-β1 and PGE2	Decrease the alanine aminotransferase level; improve allograft histology	[72]
Rat	N/A	Bone marrow	1 × 10⁷	Rat	Downregulate the levels of Th1/Th2 ratio-associated cytokines; upregulate IL-10; decrease the expression levels of IL-6, IL-17, IL-23, and TNF-α; increase the expression level of TGF-β; activate Th2 and Treg cells; inhibit the activation of Th1 and Th17 cells	Reduce the acute rejection and improve the survival rate of allogeneic LT recipients	[73]
Rat	N/A	Bone marrow	2 × 10⁶	Rat	Activate CD4+CD25+Foxp3+ Tregs	Inhibit allograft rejection; prolong the survival time of LT rats	[74]
Rat	N/A	Bone marrow	1 × 10⁶/200 g	Rat	Reduce liver graft rejection and IL-12 levels; upregulate the levels of TGF-α₁ and IL-10	Improve liver functions and survival times of rats with LT	[75]
Rat	N/A	Adipose	2.0 × 10⁶	Rat	Downregulate liver impairment and hepatocyte apoptosis; upregulate peripheral Tregs; elevate the expression levels of PCNA, IL-10 and TGF-β1; decrease the expression levels of IL-2 and IL-17	Reduce rejection rate; prolong survival time of the allograft	[76]
Rat	N/A	Bone marrow	2 × 10⁶	Rat	Upregulate PD-L1 expression; downregulate miR-17-5p	Eliminate liver allograft rejection; improve the median survival time of LT recipients	[77]
Swine	N/A	Adipose	1.0 × 10⁶	Rat	Hepatogenic differentiation of MSCs	Protect the function of liver grafts from warm ischemia/reperfusion injury; improve the viability of liver grafts	[82]
Rat	IFN-γ	Bone marrow	5 × 10⁶	Rat	Upregulate the levels of PDL-1, MHC-I, MHC-II, and CD54 and boost the immunosuppressive ability of MSCs	Alleviate acute immunologic rejection of liver grafts	[83]
Rat	Overexpression of TGF	Bone marrow	5 × 10⁶	Rat	Activate Tregs; inactivate Th17 cells	Prevent rejection of liver grafts; reduce the mortality rate of rats with LT	[84]
Rat	Overexpression of IL-10	Bone marrow	2.5 × 10⁵	Rat	Increase the expression of RORγt; decrease the expression level of FoxP3 in MSCs; downregulate the secretion of cytokines such as IL-17, IL-23, IL-6, IFN-γ and TNF-α; upregulate the secretion of cytokines such as IL-10 and TGF-β1	Prolong the mean survival time of LT rats; decrease the Banff scheme grading scores of LT rats	[85]
Rat	Overexpression of HO-1	Bone marrow	1 × 10⁷	Rat	Upregulate the levels of anti-inflammatory factors and peripheral Tregs; downregulate the levels of proinflammatory factors and NK cell viability	Upregulate the median survival time; decrease the rejection activity index	[86]
Rat	Overexpression of HO-1	Bone marrow	5 × 10⁶	Rat	Upregulate the levels of autophagy-related proteins; activate the ERK/mTOR signaling pathway	Protect against liver grafts in the reduced-size liver transplantation rat model	[87]
Rat	Overexpression of HO-1	Bone marrow	1 × 10⁶/kg	Rat	Improve the microcirculation of hepatic sinusoids; recover the energy metabolism of damaged hepatocytes	Attenuate the pathological changes and rejection rate of the transplanted liver grafts in LT models	[88]
Rat	Overexpression of HO-1	Bone marrow	5 × 10⁶	Rat	Upregulate the levels of IL-10 and TGF-β; downregulate the levels of IL-2, IL-6, IL-17, IL-23, TNF-α, and IFN-γ	Improve the liver functions and survival rates of LT recipients; reduce the degree of rejection and apoptotic cells	[89]