Copyright
©The Author(s) 2020.
World J Gastroenterol. Dec 21, 2020; 26(47): 7444-7469
Published online Dec 21, 2020. doi: 10.3748/wjg.v26.i47.7444
Published online Dec 21, 2020. doi: 10.3748/wjg.v26.i47.7444
Table 2 Strategies to enhance bone marrow-derived mesenchymal stem cell therapeutic efficiency
Ref. | Year | Pathogenesis | Model | Route | Strategy | Strategy efficiency |
[117] | 2020 | CCl4 | Mice | Tail vein | Preconditioning: Autophagy regulation in BM-MSCs | Boosted antifibrotic potential primed by autophagy inhibition in BM-MSCs may be attributed to their suppressive effect on CD4+ and CD8+ lymphocytes infiltration and HSC proliferation, which were regulated by elevated PTGS2/PGE2 via a paracrine pathway |
BM-MSC-based remedy in liver fibrosis and other inflammatory disorders | ||||||
[118] | 2019 | CCL4 | Rats | Tail vein | Preconditioning: Conditioned media | Increasing antioxidant enzyme activity |
Increased gene expression levels attenuated by CCl4 up to basal levels | ||||||
Normalized the organization apart from some dilated sinusoids and vacuolated cells | ||||||
Improved morphological, immunohistochemical, and biochemical measures | ||||||
[119] | 2016 | CCl4 | Rats | Tail vein | Preconditioning: With melatonin | Enhanced homing ability of MSCs |
Enhanced liver function | ||||||
Enhanced the interaction of melatonin receptors and matrix enzymes | ||||||
Expressed a high level of CD44 | ||||||
Ability to differentiate into adipocytes and Schwann cells | ||||||
[120] | 2017 | CCI4 | Rats | Tail vein | Preconditioning: With melatonin | High ability of homing into the injured liver (P ≤ 0.05 vs BM-MSCs) |
Higher percentage of glycogen storage but a lower percentage of collagen and lipid accumulation (P ≤ 0.05 vs CCl4 + BM-MSCs) | ||||||
Low expression of TGF-β1 and Bax and lower content of serum ALT but higher expressions of MMPs and Bcl2 | ||||||
The effectiveness of MT preconditioning in cell therapy | ||||||
[121] | 2019 | CCL4 | Rats | Tail vein | Cell-free therapy: MSC-derived macrovesicles BM- MSC-MVs | Increased serum albumin levels and VEGF quantitative gene expression (P < 0.05) |
Decreased serum ALT enzyme levels, quantitative gene expression of TGF-β, collagen-1α, and IL-1β | ||||||
Decreased the collagen deposition and improvement of the histopathological picture | ||||||
Antifibrotic, anti-inflammatory, and proangiogenic effects | ||||||
[122] | 2019 | CCl4 | Rats | Tail vein | Cell free therapy: hBM-MSCs-Ex | Inhibition of Wnt/β-catenin signaling (PPARγ, Wnt10b, Wnt3a, β-catenin) |
Downregulation of downstream gene expression (cyclin D1, WISP1) | ||||||
[123] | 2015 | CCl4 | Rats | Intravenous | Genetically modified BM-MSCs expressing TIMP-1-shRNA | Decreased TIMP-1 expression thereby regulating HSC survival |
Decreased serum levels of ALT and AST, fibrotic areas, and collagens | ||||||
Reduction of the fibrotic area | ||||||
Restoration of the liver function | ||||||
[124] | 2020 | CCl4 | Mice | Intraperitoneal injection | MSCs expressing EPO | Promoted cell viability and migration of BM-MSCs |
Enhanced antifibrotic efficacy with higher cell viability and stronger migration ability | ||||||
Alleviated liver fibrosis | ||||||
[125] | 2015 | BDL or CCl4 | Mice | Underneath the kidney capsule | Microencapsulated BM-MSCs | Activated HSCs |
Released antiapoptotic (IL-6, IGFBP-2) and anti-inflammatory (IL-1Ra) cytokines | ||||||
Decreased mRNA levels of collagen type I | ||||||
Increased levels of MMPs | ||||||
[126] | 2018 | CCl4 | Rats | Tail vein | Genetically modified BM-MSCs with human MMP-1 | Biochemical parameters and hepatic architecture improved |
Decreased collagen content | ||||||
Suppressed activation of HSCs | ||||||
Improvement of both liver injury and fibrosis | ||||||
[127] | 2016 | CCl4 | Rats | Tail vein | Human urokinase-type plasminogen activator gene-modified BM-MSCs | Decreased serum levels of ALT, AST, total bilirubin, hyaluronic acid, laminin, and procollagen type III |
Genetically modified BM-MSCs with human urokinase-type plasminogen activator | Increased levels of serum albumin | |||||
Downregulated both protein and mRNA expression of β-catenin, Wnt4, and Wnt5a | ||||||
Decreased the Wnt signaling pathway | ||||||
Decreased mRNA and protein expression of molecules involved in Wnt signaling thus working as an antifibrotic | ||||||
[128] | 2015 | TAA | Mice | Tail vein | Genetically modified BM-MSCs, MSCs engineered to produce IGF-I | Enhanced the effects of MSC transplantation |
Decreased inflammatory responses | ||||||
Decreased collagen deposition | ||||||
Increased growth factor like-I, IGF-I, and HGF | ||||||
Reduced fibrogenesis and the stimulation of hepatocellular proliferation | ||||||
[129] | 2017 | CCl4, BDL | Mice | Intraperitoneal | BM-MSCs triggered by sphingosine 1-phosphate | Increased HuR expression and cytoplasmic localization |
S1P-induced migration of HBM-MSCs via S1PR3 and HuR | ||||||
HuR regulated S1PR3 mRNA expression by binding with S1PR3 mRNA 3’ UTR | ||||||
S1P-induced HuR phosphorylation and cytoplasmic translocation via S1PR3 | ||||||
HuR regulated S1PR3 expression by competing with miR-30e |
- Citation: Al-Dhamin Z, Liu LD, Li DD, Zhang SY, Dong SM, Nan YM. Therapeutic efficiency of bone marrow-derived mesenchymal stem cells for liver fibrosis: A systematic review of in vivo studies. World J Gastroenterol 2020; 26(47): 7444-7469
- URL: https://www.wjgnet.com/1007-9327/full/v26/i47/7444.htm
- DOI: https://dx.doi.org/10.3748/wjg.v26.i47.7444