USP9X-enriched MSC-sEV inhibits LSEC angiogenesis in MASH mice by downregulating the IκBα/NF-κB/Ang-2 pathway.

Pathological angiogenesis of liver sinusoidal endothelial cells (LSEC) plays a crucial role in the progression of metabolic dysfunction-associated steatohepatitis (MASH)-induced liver fibrosis. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) have shown promising therapeutic potential against MASH. This study aimed to investigate the impact of MSC-sEV on LSEC angiogenesis and elucidate the underlying molecular mechanisms.

MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression.

Liver fibrosis is a significant health burden, marked by the consistent deposition of collagen. Unfortunately, the currently available treatment approaches for this condition are far from optimal. Lysyl oxidase-like protein 2 (LOXL2) secreted by hepatic stellate cells (HSCs) is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.

Lipotoxic hepatocyte derived LIMA1 enriched small extracellular vesicles promote hepatic stellate cells activation via inhibiting mitophagy.

Background: Hepatic stellate cells (HSCs) play a crucial role in the development of fibrosis in non-alcoholic fatty liver disease (NAFLD). Small extracellular vesicles (sEV) act as mediators for intercellular information transfer, delivering various fibrotic factors that impact the function of HSCs in liver fibrosis. In this study, we investigated the role of lipotoxic hepatocyte derived sEV (LTH-sEV) in HSCs activation and its intrinsic mechanisms.

RNF31 alleviates liver steatosis by promoting p53/BNIP3-related mitophagy in hepatocytes.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is one of the liver illnesses that may be affected by mitophagy, which is the selective removal of damaged mitochondria. RNF31, an E3 ubiquitin ligase, is carcinogenic in many malignancies. However, the influence of RNF31 on mitochondrial homeostasis and NAFLD development remains unknown.

Mesenchymal stem cell-derived exosomal miR-27b-3p alleviates liver fibrosis via downregulating YAP/LOXL2 pathway.

Lysyl oxidase-like 2 (LOXL2) is an extracellular copper-dependent enzyme that plays a central role in fibrosis by catalyzing the crosslinking and deposition of collagen. Therapeutic LOXL2 inhibition has been shown to suppress liver fibrosis progression and promote its reversal. This study investigates the efficacy and underlying mechanisms of human umbilical cord-derived exosomes (MSC-ex) in LOXL2 inhibition of liver fibrosis.

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

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) affects nearly a quarter of the population with no approved pharmacological therapy. Liver steatosis is a primary characteristic of NAFLD. Recent studies suggest that human umbilical cord mesenchymal stem cell-derived exosomes (MSC-ex) may provide a promising strategy for treating liver injury; however, the role and underlying mechanisms of MSC-ex in steatosis are not fully understood.

Mitochondrial transplantation: opportunities and challenges in the treatment of obesity, diabetes, and nonalcoholic fatty liver disease.

Metabolic diseases, including obesity, diabetes, and nonalcoholic fatty liver disease (NAFLD), are rising in both incidence and prevalence and remain a major global health and socioeconomic burden in the twenty-first century. Despite an increasing understanding of these diseases, the lack of effective treatments remains an ongoing challenge. Mitochondria are key players in intracellular energy production, calcium homeostasis, signaling, and apoptosis.

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Accelerate Cutaneous Wound Healing by Enhancing Angiogenesis through Delivering Angiopoietin-2.

The underlying mechanisms of human umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes (hucMSC-Exs), which play significant roles in skin wound healing, remain poorly understood. By using a rat model of deep second-degree burn injury, the roles of hucMSC-Exs in angiogenesis and cutaneous wound healing in vivo were investigated. We found that hucMSC-Exs accelerated skin wound healing and angiogenesis, inducing a higher wound-closure rate and increased expression of CD31 in vivo.