hucMSC Exosome-Derived GPX1 Is Required for the Recovery of Hepatic Oxidant Injury

Abstract

Exosomes are small biological membrane vesicles secreted by various cells, including mesenchymal stem cells (MSCs). We previously reported that MSC-derived exosomes (MSC-Ex) can elicit hepatoprotective effects against toxicant-induced injury. However, the success of MSC-Ex-based therapy for treatment of liver diseases and the underlying mechanisms have not been well characterized. We used human umbilical cord MSC-derived exosome (hucMSC-Ex) administrated by tail vein or oral gavage at different doses and, in engrafted liver mouse models, noted antioxidant and anti-apoptotic effects and rescue from liver failure. A single systemic administration of hucMSC-Ex (16 mg/kg) effectively rescued the recipient mice from carbon tetrachloride (CCl 4 )-induced liver failure. Moreover, hucMSC-Ex-derived glutathione peroxidase1 (GPX1), which detoxifies CCl 4 and H 2 O 2 , reduced oxidative stress and apoptosis. Knockdown of GPX1 in hucMSCs abrogated antioxidant and anti-apoptotic abilities of hucMSC-Ex and diminished the hepatoprotective effects of hucMSC-Ex in vitro and in vivo. Thus, hucMSC-Ex promote the recovery of hepatic oxidant injury through the delivery of GPX1.

Exosomes as a novel pathway for regulating development and diseases of the skin (Review)

“…For instance, exosome mRNA may be used as a diagnostic marker for lung cancer (13), exosome-derived glutathione peroxidase 1 may restore hepatic oxidant injury (14), and exosomal glypican 1 and its regulatory miRNAs may be specific markers for the detection and targeted therapy of colorectal cancer (15). With further study, the clinical applications of exosome markers may be increased.…”

Mesenchymal stem cell derived extracellular vesicles: a promising new therapeutic approach for hepatic injury

“…MSC from adipose tissue or from umbilical cord MSCs are less invasive to obtain and can be isolated at a lower cost compared with bone marrow derived MSC. They retain the multipotency and immunoregulatory activities, as well as the functional outcomes observed with bone-marrow derived MSC (1,6). …”

“…The use of mesenchymal stem cell (MSC) based therapy is a promising new strategy for the treatment of organ injury, and one that may have applications for acute hepatic injury (1–3). MSC have several unique properties such as their inherent capacity for regeneration and multipotency that support their use for tissue replacement therapy.…”

“…EV have been postulated to contribute to many physiological and pathological processes such as cancer progression, immune modulation, neurodegenerative diseases, or tissue regeneration (1,2,7,8). EV released from stem cells have been shown to modulate angiogenesis, prevent apoptosis or promote cell proliferation.…”

“…In a recent article, Xu and co-workers examined the effect of human umbilical cord mesenchymal stem cell derived exosomes (hucMSC-Ex) on hepatic injury using both in vivo and in vitro models (1). They showed that hucMSC-Ex could protect against hydrogen peroxide (H 2 O 2 ) induced cell death, and in liver injury in mice induced by administering carbon tetrachloride (CCl 4 ) (13,14).…”