Application potential of stem/progenitor cell-derived extracellular vesicles in renal diseases

Abstract

Extracellular vesicles (EVs) are nanometer-sized and membrane-bound vesicles, including exosomes and microvesicles. EVs can deliver bioactive macromolecules such as proteins, lipids, and nucleic acids, allowing intercellular communication in multicellular organisms. EVs are secreted by all cell types including stem/progenitor cells. Stem/progenitor cell-derived EVs have been identified to exert immunomodulatory effects on target cells through transferring protein molecules as well as regulatory effects on the phenotype of target cells through fusion with the target cells membrane and/or through direct endocytosis by target cells to transfer nucleic acid substances (such as mRNA, miRNA) to the target cells. In both human and animal models, the use of stem/progenitor cells (such as bone marrow mesenchymal stromal cells) has been shown to promote the recovery of kidney diseases such as acute kidney injury and chronic kidney disease. Stem/progenitor cell-derived extracellular vesicles are an important mechanism by which stem/progenitor cells might repair kidney injury. Here, this review will discuss the latest advances concerning the application potential of stem/progenitor cell-derived extracellular vesicles in renal diseases, including the aspects as follows: anti-inflammatory, proliferation-promoting and anti-apoptotic, proangiogenic, antifibrotic and renal cancer progression-promoting. Therefore, stem/progenitor cell-derived extracellular vesicles may be a promising treatment tool for renal diseases.

Three-dimensional culture of MSCs produces exosomes with improved yield and enhanced therapeutic efficacy for cisplatin-induced acute kidney injury

“…MSCexos have shown excellent efficacy in tissue repair and regeneration of many organs, including liver, lung, cartilage, myocardium, brain, spinal cord, and kidney [15][16][17][18][19][20][21][22]. Taking acute kidney injury (AKI) as an example, MSC-exos exert a series of renoprotective and regenerative effects through various mechanisms, including anti-inflammatory, immunomodulatory, anti-necroptosis, anti-apoptosis, and promoting cell proliferation [15,23]. To date, administration of MSC-exos effectively improves clinical outcomes in patients suffering from graft-versus-host disease and chronic kidney diseases [24,25].…”

“…In particular, it is shown that the therapeutic effect of MSC-exos is similar to that of MSCs [1], without the drawbacks of MSC-based therapy, such as unwanted differentiation of engrafted MSCs and embolism. Additionally, MSC-exos possess the characteristic of lower immunogenicity because they lack the antigens on the surface membrane [1,15]. Therefore, they are likely to represent a novel cell-free therapeutic agent for many human diseases.…”

“…Meanwhile, unlike immortal cells lines, the expansion of MSCs is limited in culture and only cells within passage 6 can be used according to most studies [29,30]. Therefore, the low yield and the lack of an established biomanufacturing platform to produce sufficient MSC-exos remain major challenges, which currently limit their therapeutic application [8,15,31].…”

Stem/progenitor cell‐mediated pulpal tissue regeneration: a systematic review and meta‐analysis

“…), renal diseases (Sun et al . ), autoimmune diseases (Rad et al . ) and periodontitis (Fawzy El‐Sayed et al .…”

“…Therapeutic transplantation of stem/progenitor cells has been experimentally applied in the treatment of a variety of medical conditions with encouraging results, including inflammatory bowel diseases (Kang et al 2018), renal diseases (Sun et al 2019), autoimmune diseases (Rad et al 2019) and periodontitis (Fawzy El-Sayed et al 2012, 2015a. Ongoing advances in tissue engineering carrier/scaffolds, biomolecules and cellular transplantation approaches may have paved the way for a stem/progenitor cellmediated pulpal regeneration, too (Fawzy El-Sayed et al 2015a,b, Conde et al 2016, Galler 2016.…”