Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm

Yin, Kan; Wang, Shihua; Zhao, Robert Chunhua

doi:10.1186/s40364-019-0159-x

Cited by 293 publications

(236 citation statements)

References 64 publications

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“…The absence of these proteins on the exosomal surface suggests no immune rejection can be expected for allogeneic therapeutics [32][33][34][35]. Exosomes derived from stem cells are actively being developed as a cell-free therapy because they recapitulate the functions of stem cells such as repair, regeneration, anti-inflation, and immune modulation without the limitations and risks of stem cells themselves [30,31,36,37]. As an example, exosomes derived from MSCs have therapeutic effects on various diseases including myocardial infarction [6,38], CCl4-induced liver injury [39], graft-versus-host disease (GvHD) [20], acute and chronic kidney injury [40], and atopic dermatitis [34,41].…”

Section: Exosomes and Extracellular Vesiclesmentioning

confidence: 99%

Advances in Analysis of Biodistribution of Exosomes by Molecular Imaging

Yi¹,

Lee²,

Kim

et al. 2020

IJMS

146

131

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Exosomes are nano-sized membranous vesicles produced by nearly all types of cells. Since exosome-like vesicles are produced in an evolutionarily conserved manner for information and function transfer from the originating cells to recipient cells, an increasing number of studies have focused on their application as therapeutic agents, drug delivery vehicles, and diagnostic targets. Analysis of the in vivo distribution of exosomes is a prerequisite for the development of exosome-based therapeutics and drug delivery vehicles with accurate prediction of therapeutic dose and potential side effects. Various attempts to evaluate the biodistribution of exosomes obtained from different sources have been reported. In this review, we examined the current trends and the advantages and disadvantages of the methods used to determine the biodistribution of exosomes by molecular imaging. We also reviewed 29 publications to compare the methods employed to isolate, analyze, and label exosomes as well as to determine the biodistribution of labeled exosomes.

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Section: Exosomes and Extracellular Vesiclesmentioning

confidence: 99%

Advances in Analysis of Biodistribution of Exosomes by Molecular Imaging

Yi¹,

Lee²,

Kim

et al. 2020

IJMS

146

131

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show abstract

“…Accumulating evidence has strongly revealed that exosomes derived from stem cells are safe and effective for treating renal diseases in rat and mouse models [8,9]. Exosomes secreted by MSCs have a significant protective effect on renal injury in both acute kidney injury (AKI) and chronic kidney disease [8,10].…”

Section: Introductionmentioning

confidence: 99%

Exosomal miRNA-215-5p Derived from Adipose-Derived Stem Cells Attenuates Epithelial–Mesenchymal Transition of Podocytes by Inhibiting ZEB2

Jin

Wang

Zhao

et al. 2020

BioMed Research International

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Background. Podocyte migration is actively involved in the process of podocyte loss and proteinuria production, which is closely associated with the development of diabetic nephropathy (DN). Exosomes from adipose-derived stem cells (ADSCs-Exos) effectively inhibit podocyte apoptosis in the treatment of DN. However, how ADSCs-Exos affect the migration of podocytes is obscure. This study is aimed at exploring the regulatory role of ADSCs-Exos on cell migration and the underlying mechanism. Methods. ADSCs-Exo was authenticated by transmission electron microscopy (TEM), western blotting, and flow cytometry. Cell viability and migration ability of podocytes were measured by CCK8 and Transwell assays, respectively. Relative expressions of miRNAs and mRNAs were determined by qRT-PCR. The transmitting between PKH26-labeled exosome and podocytes was evaluated by IF assay. Dual luciferase reporter assay was employed to detect the relationship between miR-215-5p and ZEB2. Results. The exposure to serum from DN patient (hDN-serum) significantly inhibited cell viability of podocytes, but ADSCs-Exo addition notably blunts cytotoxicity induced by the transient stimulus of hDN-serum. Besides, ADSCs-Exo administration powerfully impeded high glucose-(HG-) induced migration and injury of podocyte. With the podocyte dysfunction, several miRNAs presented a significant decline under the treatment of HG including miR-251-5p, miR-879-5p, miR-3066-5p, and miR-7a-5p, all of which were rescued by the addition of ADSCs-Exo. However, only miR-251-5p was a key determinant in the process of ADSCs-Exo-mediated protective role on podocyte damage. The miR-251-5p inhibitor counteracted the improvement from the ADSCs-Exo preparation on HG-induced proliferation inhibition and migration promotion. Additionally, miR-215-5p mimics alone remarkably reversed HG-induced EMT process of podocyte. Mechanistically, we confirmed that ADSCs-Exos mediated the shuttling of miR-215-5p to podocyte, thereby protecting against HG-induced metastasis, possibly through inhibiting the transcription of ZEB2. Conclusion. ADSCs-Exo has the protective effect on HG-evoked EMT progression of podocytes thru a mechanism involving ZEB2. Potentially, the ADSCs-Exo preparation is a useful therapeutic strategy for improving podocyte dysfunction and DN symptoms clinically.

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“…Current knowledge on mesenchymal stromal cells (MSCs) as future medicinal products in the field of regenerative medicine sheds light on the crucial role of their secreted factors and extracellular vesicles (EVs) to stimulate tissues and cells. In particular, by avoiding the concerns of using live and replicating cells that may undergo mal-differentiation or mutation, the idea of EVs as therapeutics is being explored, since they can mimic several biological actions of MSCs [1] through embedded lipids, proteins, mRNAs and miRNAs [2,3], therefore acting as biological nanocarriers. Even more intriguing, MSC-EVs may be engineered by either exogenous load [4] or reprogramming of the secreting cells [5,6] to shuttle and deliver specific and therapeutic molecules, such as miRNAs or mRNAs, eventually driving the focused influence on target cells [7].…”

Section: Introductionmentioning

confidence: 99%

miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

et al. 2020

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Human amniotic membrane and amniotic membrane-derived mesenchymal stromal cells (hAMSCs) have produced promising results in regenerative medicine, especially for the treatment of inflammatory-based diseases and for different injuries including those in the orthopedic field such as tendon disorders. hAMSCs have been proposed to exert their anti-inflammatory and healing potential via secreted factors, both free and conveyed within extracellular vesicles (EVs). In particular, EV miRNAs are considered privileged players due to their impact on target cells and tissues, and their future use as therapeutic molecules is being intensely investigated. In this view, EV-miRNA quantification in either research or future clinical products has emerged as a crucial paradigm, although, to date, largely unsolved due to lack of reliable reference genes (RGs). In this study, a panel of thirteen putative miRNA RGs (let-7a-5p, miR-16-5p, miR-22-5p, miR-23a-3p, miR-26a-5p, miR-29a-5p, miR-101-3p, miR-103a-3p, miR-221-3p, miR-423-5p, miR-425-5p, miR-660-5p and U6 snRNA) that were identified in different EV types was assessed in hAMSC-EVs. A validated experimental pipeline was followed, sifting the output of four largely accepted algorithms for RG prediction (geNorm, NormFinder, BestKeeper and ΔCt method). Out of nine RGs constitutively expressed across all EV isolates, miR-101-3p and miR-22-5p resulted in the most stable RGs, whereas miR-423-5p and U6 snRNA performed poorly. miR-22-5p was also previously reported to be a reliable RG in adipose-derived MSC-EVs, suggesting its suitability across samples isolated from different MSC types. Further, to shed light on the impact of incorrect RG choice, the level of five tendon-related miRNAs (miR-29a-3p, miR-135a-5p, miR-146a-5p, miR-337-3p, let-7d-5p) was compared among hAMSC-EVs isolates. The use of miR-423-5p and U6 snRNA did not allow a correct quantification of miRNA incorporation in EVs, leading to less accurate fingerprinting and, if used for potency prediction, misleading indication of the most appropriate clinical batch. These results emphasize the crucial importance of RG choice for EV-miRNAs in hAMSCs studies and contribute to the identification of reliable RGs such as miR-101-3p and miR-22-5p to be validated in other MSC-EVs related fields.

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Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm

Cited by 293 publications

References 64 publications

Advances in Analysis of Biodistribution of Exosomes by Molecular Imaging

Advances in Analysis of Biodistribution of Exosomes by Molecular Imaging

Exosomal miRNA-215-5p Derived from Adipose-Derived Stem Cells Attenuates Epithelial–Mesenchymal Transition of Podocytes by Inhibiting ZEB2

miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

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