Reproducible Large-Scale Isolation of Exosomes from Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells and Their Application in Acute Kidney Injury

Abstract

<jats:p>Acute kidney injury (AKI) is a fatal medical episode caused by sudden kidney damage or failure, leading to the death of patients within a few hours or days. Previous studies demonstrated that exosomes derived from various mesenchymal stem/stromal cells (MSC-exosomes) have positive effects on renal injuries in multiple experimental animal models of kidney diseases including AKI. However, the mass production of exosomes is a challenge not only in preclinical studies with large animals but also for successful clinical applications. In this respect, tangential flow filtration (TFF) is suitable for good manufacturing practice (GMP)-compliant large-scale production of high-quality exosomes. Until now, no studies have been reported on the use of TFF, but rather ultracentrifugation has been almost exclusively used, to isolate exosomes for AKI therapeutic application in preclinical studies. Here, we demonstrated the reproducible large-scale production of exosomes derived from adipose tissue-derived MSC (ASC-exosomes) using TFF and the lifesaving effect of the ASC-exosomes in a lethal model of cisplatin-induced rat AKI. Our results suggest the possibility of large-scale stable production of ASC-exosomes without loss of function and their successful application in life-threatening diseases.</jats:p>

Comprehensive Proteomic Analysis of Exosomes Derived from Human Bone Marrow-, Adipose Tissue-, and Umbilical Cord- Mesenchymal Stem Cells

“…Previous studies described the role of AT-MSC exo in immune dysregulation, oxidative stress, and in ammation [41,42]. Lee et al showed that AT-MSCs had the ability to stably produce exosomes, and PRDX 1, 2, 4, and 6 exerted antioxidant activity to protect the kidney during acute injury [42]. Our data further con rm that exosomes play a role in immunity primarily by the regulation of leukocyte-mediated immunity.…”

“…Considering their easy availability and fewer ethical issues, AT-MSCs may present a good choice for mass production of exosomes. Previous studies described the role of AT-MSC exo in immune dysregulation, oxidative stress, and in ammation [41,42]. Lee et al showed that AT-MSCs had the ability to stably produce exosomes, and PRDX 1, 2, 4, and 6 exerted antioxidant activity to protect the kidney during acute injury [42].…”

Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells Alleviate Acetaminophen-induced Acute Liver Failure Through Activating ERK and IGF-1R/PI3K/AKT Signaling Pathways

“…Growing evidence indicates the importance of MSC-Exo in disease treatment. Recently, it has been demonstrated that adipose and bone marrow MSC-derived exosomes have positive effects on wound healing pricess [40], acute kidney injury [41] , osteoarthritis [42], angiogenesis [43], liver brosis [44] and so on. hUCMSCs can secrete exosomes during various biological processes and hUCMSC-Exo also have emerged as potential therapeutic agents [45,46].…”

Small Extracellular Vesicles From Human Adipose-derived Stem Cells: A Potential Promoter of Keeping Fat Graft Survival

“…Among various separation methods, tangential ow ltration (TFF) is considered as an ideal method for industrial-scale production of sEVs [51][52][53]. TFF can provide GMP level sEVs from a large amount of CM [54]. Some studies have even shown that sEVs separated by TFF have higher yield and activity than those separated by ultracentrifugation [42,55].…”