Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate liver steatosis by promoting fatty acid oxidation and reducing fatty acid synthesis

Yang, Fuji; Wu, Yanshuang; Chen, Yifei; Xi, Jianbo; Chu, Ying Hao; Jin, Jianhua; Yan, Yongmin

doi:10.1016/j.jhepr.2023.100746

Cited by 26 publications

(10 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Oleic and palmitic acid (OPA)-stimulated AML12 cells are a well-established hyperlipidemic model for this purpose . OPA is known to induce significant lipid accumulation within liver cells by promoting intracellular triglyceride (TG) and total cholesterol (TC) synthesis . Upon 24 h exposure to 300 μM OPA (OA:PA = 3:1), model groups displayed a marked elevation in intracellular TG and TC levels when compared to the nonstimulated controls.…”

Section: Resultsmentioning

confidence: 99%

“…17 OPA is known to induce significant lipid accumulation within liver cells by promoting intracellular triglyceride (TG) and total cholesterol (TC) synthesis. 18 Upon 24 h exposure to 300 μM OPA (OA:PA = 3:1), model groups displayed a marked elevation in intracellular TG and TC levels when compared to the nonstimulated controls. As depicted in Figure 2, PF-06649298 failed to mitigate the induced lipid accumulation.…”

Section: Effect On Lipidmentioning

confidence: 94%

See 1 more Smart Citation

Discovery of Highly Potent Solute Carrier 13 Member 5 (SLC13A5) Inhibitors for the Treatment of Hyperlipidemia

Zhang,

Hu,

Guo

et al. 2024

J. Med. Chem.

View full text Add to dashboard Cite

In the face of escalating metabolic disease prevalence, largely driven by modern lifestyle factors, this study addresses the critical need for novel therapeutic approaches. We have identified the sodium-coupled citrate transporter (NaCT or SLC13A5) as a target for intervention. Utilizing rational drug design, we developed a new class of SLC13A5 inhibitors, anchored by the hydroxysuccinic acid scaffold, refining the structure of PF-06649298. Among these, LBA-3 emerged as a standout compound, exhibiting remarkable potency with an IC 50 value of 67 nM, significantly improving upon PF-06649298. In vitro assays demonstrated LBA-3's efficacy in reducing triglyceride levels in OPA-induced HepG2 cells. Moreover, LBA-3 displayed superior pharmacokinetic properties and effectively lowered triglyceride and total cholesterol levels in diverse mouse models (PCN-stimulated and starvationinduced), without detectable toxicity. These findings not only spotlight LBA-3 as a promising candidate for hyperlipidemia treatment but also exemplify the potential of targeted molecular design in advancing metabolic disorder therapeutics.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Effect On Lipidmentioning

confidence: 94%

Discovery of Highly Potent Solute Carrier 13 Member 5 (SLC13A5) Inhibitors for the Treatment of Hyperlipidemia

Zhang,

Hu,

Guo

et al. 2024

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

“…Here we present 3D culture of umbilical cord-derived SCs, mainly UCMSCs and umbilical cord blood MSCs (UCBMSCs). Similar to BMMSC-EVs, EVs derived from 2D cultured UCMSCs have been found to exert protective effects in various ways, such as acute and chronic renal injury, heart injury, liver injury, brain injury, and immunomodulation, as well as alleviation of type 2 diabetes mellitus [ 23 , 173 – 179 ]. As with BMMSCs, in an in vivo wound healing model, EVs derived from 3D spheroid culture and 3D spinner flask culture of UCMSCs were able to promote epithelialization of wounds and accelerate post-injury skin healing, with a more dramatic effect than 2D-EVs [ 147 , 163 ].…”

Section: Current Applications Of Evs Derived From 3d Cultured Scsmentioning

confidence: 99%

Advances in the application of extracellular vesicles derived from three-dimensional culture of stem cells

Chen,

Wu,

Jin

et al. 2024

J Nanobiotechnol

View full text Add to dashboard Cite

Stem cells (SCs) have been used therapeutically for decades, yet their applications are limited by factors such as the risk of immune rejection and potential tumorigenicity. Extracellular vesicles (EVs), a key paracrine component of stem cell potency, overcome the drawbacks of stem cell applications as a cell-free therapeutic agent and play an important role in treating various diseases. However, EVs derived from two-dimensional (2D) planar culture of SCs have low yield and face challenges in large-scale production, which hinders the clinical translation of EVs. Three-dimensional (3D) culture, given its ability to more realistically simulate the in vivo environment, can not only expand SCs in large quantities, but also improve the yield and activity of EVs, changing the content of EVs and improving their therapeutic effects. In this review, we briefly describe the advantages of EVs and EV-related clinical applications, provide an overview of 3D cell culture, and finally focus on specific applications and future perspectives of EVs derived from 3D culture of different SCs. Graphical Abstract

show abstract

“…Noteworthy, human umbilical cord MSC-EXOs mitigated DSS-induced IBD by lessening macrophage pyroptosis via modulation of miR-378a-5p/NLRP3 pathway (Cai et al 2021 ). Moreover, Yang et al ( 2021 ) pointed to the anti-inflammatory effect of TNF-α-stimulated gene 6 in human umbilical cord MSC-EXOs that succeeded to mitigate UC in addition to intestinal function and immune homeostasis. In addition, olfactory ecto-MSCs-EXOs alleviated experimental colitis via suppressing differentiation of proinflammatory Th1/Th17 cells and inducing differentiation of anti-inflammatory Treg cells (Tian et al 2020 ).…”

Section: Applications Of Msc-evs In Different Models Of Gi Diseasesmentioning

confidence: 99%

Innovative preconditioning strategies for improving the therapeutic efficacy of extracellular vesicles derived from mesenchymal stem cells in gastrointestinal diseases

Didamoony,

Soubh,

Atwa

et al. 2023

Inflammopharmacol

View full text Add to dashboard Cite

Gastrointestinal (GI) diseases have become a global health issue and an economic burden due to their wide distribution, late prognosis, and the inefficacy of recent available medications. Therefore, it is crucial to search for new strategies for their management. In the recent decades, mesenchymal stem cells (MSCs) therapy has attracted attention as a viable option for treating a myriad of GI disorders such as hepatic fibrosis (HF), ulcerative colitis (UC), acute liver injury (ALI), and non-alcoholic fatty liver disease (NAFLD) due to their regenerative and paracrine properties. Importantly, recent studies have shown that MSC-derived extracellular vesicles (MSC-EVs) are responsible for most of the therapeutic effects of MSCs. In addition, EVs have revealed several benefits over their parent MSCs, such as being less immunogenic, having a lower risk of tumour formation, being able to cross biological barriers, and being easier to store. MSC-EVs exhibited regenerative, anti-oxidant, anti-inflammatory, anti-apoptotic, and anti-fibrotic effects in different experimental models of GI diseases. However, a key issue with their clinical application is the maintenance of their stability and efficacy following in vivo transplantation. Preconditioning of MSC-EVs or their parent cells is one of the novel methods used to improve their effectiveness and stability. Herein, we discuss the application of MSC-EVs in several GI disorders taking into account their mechanism of action. We also summarise the challenges and restrictions that need to be overcome to promote their clinical application in the treatment of various GI diseases as well as the recent developments to improve their effectiveness. Graphical abstract A representation of the innovative preconditioning techniques that have been suggested for improving the therapeutic efficacy of MSC-EVs in GI diseases. The pathological conditions in various GI disorders (ALI, UC, HF and NAFLD) create a harsh environment for EVs and their parents, increasing the risk of apoptosis and senescence of MSCs and thereby diminishing MSC-EVs yield and restricting their large-scale applications. Preconditioning with pharmacological agents or biological mediators can improve the therapeutic efficacy of MSC-EVs through their adaption to the lethal environment to which they are subjected. This can result in establishment of a more conducive environment and activation of numerous vital trajectories that act to improve the immunomodulatory, reparative and regenerative activities of the derived EVs, as a part of MSCs paracrine system. ALI, acute liver injury; GI diseases, gastrointestinal diseases; HF, hepatic fibrosis; HSP, heat shock protein; miRNA, microRNA; mRNA, messenger RNA; MSC-EVs, mesenchymal stem cell-derived extracellular vesicles; NAFLD, non-alcoholic fatty liver disease; UC, ulcerative colitis.

show abstract

Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate liver steatosis by promoting fatty acid oxidation and reducing fatty acid synthesis

Cited by 26 publications

References 42 publications

Discovery of Highly Potent Solute Carrier 13 Member 5 (SLC13A5) Inhibitors for the Treatment of Hyperlipidemia

Discovery of Highly Potent Solute Carrier 13 Member 5 (SLC13A5) Inhibitors for the Treatment of Hyperlipidemia

Advances in the application of extracellular vesicles derived from three-dimensional culture of stem cells

Innovative preconditioning strategies for improving the therapeutic efficacy of extracellular vesicles derived from mesenchymal stem cells in gastrointestinal diseases

Contact Info

Product

Resources

About