scholarly journals Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hisanori Muto ◽  
Takanori Ito ◽  
Taku Tanaka ◽  
Shinya Yokoyama ◽  
Kenta Yamamoto ◽  
...  

AbstractNon-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α, Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes.

PLoS ONE ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. e0238449 ◽  
Author(s):  
Suleiman Alhaji Muhammad ◽  
Norshariza Nordin ◽  
Paisal Hussin ◽  
Muhammad Zulfadli Mehat ◽  
Noor Hayaty Abu Kasim ◽  
...  

2013 ◽  
Vol 12 (1) ◽  
Author(s):  
Dr. Nurul Asma Abdullah

Introduction: Stem cells from human exfoliated deciduous teeth (SHED) are highly proliferative, clonogenic cells capable of differentiating into osteoblasts and inducing bone formation. It is a potential alternative for stem cell bone regeneration therapy. However, stem cell therapy carries the risk of immune rejection mediated by inflammatory cytokines of the human defense system. Objective: This preliminary research studies the interaction between SHED and the immune system by determining the inflammatory cytokines profile and osteogenic potential of SHED. Methods: Human fetal osteoblasts (hFOb) cell line and isolated SHED were cultured and total RNA was extracted, followed by reverse transcription cDNA synthesis. Semi-quantitative reverse transcription PCR and Multiplex PCR were performed to detect the expression levels of OPG/RANKL and TNF-α, IL-1β, IL-6, IL-8 and TGF-β in both cell types. Results: Analysis showed that SHED expressed significantly lower amounts of IL-1β, IL-6, and IL-8 compared to hFOB. IL-1β is a potent bone-resorbing factor, while IL-6 and IL-8 induce osteoclastogenesis and osteolysis respectively. SHED did not express TNF-α which stimulates osteoclastic activity. SHED demonstrated high OPG/RANKL ratio, in contrast with that of marrow stem cells described in previous studies. Our findings suggest that SHED may have improved immunomodulatory profile in terms of promoting relatively lower inflammatory reaction during transplant and enhancing bone regeneration. Conclusion: SHED has a potential to be a good source of osteoblasts for bone regeneration therapy. Further studies on the immunomodulatory properties of SHED-derived osteoblasts are necessary to enable stem cell therapy in immunocompetent hosts


Author(s):  
Minu Anoop ◽  
Indrani Datta

: Most conventional treatments for neurodegenerative diseases fail due to their focus on neuroprotection rather than neurorestoration. Stem cell‐based therapies are becoming a potential treatment option for neurodegenerative diseases as they can home in, engraft, differentiate and produce factors for CNS recovery. Stem cells derived from human dental pulp tissue differ from other sources of mesenchymal stem cells due to their embryonic neural crest origin and neurotrophic property. These include both dental pulp stem cells [DPSCs] from dental pulp tissues of human permanent teeth and stem cells from human exfoliated deciduous teeth [SHED]. SHED offer many advantages over other types of MSCs such as good proliferative potential, minimal invasive procurement, neuronal differentiation and neurotrophic capacity, and negligible ethical concerns. The therapeutic potential of SHED is attributed to the paracrine action of extracellularly released secreted factors, specifically the secretome, of which exosomes is a key component. SHED and its conditioned media can be effective in neurodegeneration through multiple mechanisms, including cell replacement, paracrine effects, angiogenesis, synaptogenesis, immunomodulation, and apoptosis inhibition, and SHED exosomes offer an ideal refined bed-to-bench formulation in neurodegenerative disorders. However, in spite of these advantages, there are still some limitations of SHED exosome therapy, such as the effectiveness of long-term storage of SHED and their exosomes, the development of a robust GMP-grade manufacturing protocol, optimization of the route of administration, and evaluation of the efficacy and safety in humans. In this review, we have addressed the isolation, collection and properties of SHED along with its therapeutic potential on in vitro and in vivo neuronal disorder models as evident from the published literature.


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