Background
Activation of innate or adaptive immune cells in vivo
Activation of innate immune cells in vivo
Activation of adaptive immune cells in vivo
Regulation of immune cells in response to LT
The interaction between MSCs and immune cells
The interaction between MSCs and innate immune cells
The interaction between MSCs and adaptive immune cells
MSC transplantation for improvement in LT prognosis
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] |