Treatment of Chronic Kidney Disease with Extracellular Vesicles from Mesenchymal Stem Cells and CD133+ Expanded Cells: A Comparative Preclinical Analysis

Miyasaki, Dayane Mayumi; Senegaglia, Alexandra Cristina; Moura, Sérgio Adriane Bezerra de; Leitolis, Amanda; Capriglione, Luiz Guilherme Achcar; Fracaro, Letícia; Leite, Lidiane Maria Boldrini; Utumi, Paulo Henrique; Fragoso, Felipe Yukio Ishikawa; Meyer, Fernando; Correa, Alejandro; Brofman, Paulo Roberto Slud

doi:10.3390/ijms23052521

Cited by 12 publications

(9 citation statements)

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“…Different EVs have been used to treat different diseases [ 84 , 85 , 86 , 87 ]; however, to date, there is no definition of which EV source is the best and for which disease or injury. Our group has previously shown the potential of E-CD133 EVs in the treatment of cardiac injury, in a rat model of myocardial infarction [ 88 ], and in the recovery of renal function, in a rat model of chronic kidney disease [ 26 ]. Future experiments will be able to further assess the relationship between miRNAs (and proteins) identified in E-CD133 EVs, their targets and modulated pathways, and the effects already described.…”

Section: Resultsmentioning

confidence: 99%

“…E-CD133 is a promising cell population little explored in the literature so far. We recently demonstrated the potential of E-CD133 and their EVs in the treatment of cardiac and renal lesions [ 21 , 26 ]. Here, we extended the characterization of E-CD133 EVs by analyzing their miRNA cargo.…”

Section: Resultsmentioning

confidence: 99%

“…The EV components can participate not only in various physiological processes such as homeostasis, inflammation, immunological interactions, and angiogenesis, but also in pathophysiological conditions involved in the development of cancer and metastasis, autoimmune diseases, and infections of various types [ 13 , 14 , 15 , 16 , 17 , 18 ]. EVs isolated from stem and endothelial progenitors have been tested in several disease models and shown to protect and/or repair kidney, nervous and heart tissue after injury, among other tissues and organs [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. On the downside, however, EVs can also help in preparing the niche for metastases, for example [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Selective Loading and Variations in the miRNA Profile of Extracellular Vesicles from Endothelial-like Cells Cultivated under Normoxia and Hypoxia

Robert

Marcon

Angulski

et al. 2022

IJMS

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Endothelial-like cells may be obtained from CD133+ mononuclear cells isolated from human umbilical cord blood (hUCB) and expanded using endothelial-inducing medium (E-CD133 cells). Their use in regenerative medicine has been explored by the potential not only to form vessels but also by the secretion of bioactive elements. Extracellular vesicles (EVs) are prominent messengers of this paracrine activity, transporting bioactive molecules that may guide cellular response under different conditions. Using RNA-Seq, we characterized the miRNA content of EVs derived from E-CD133 cells cultivated under normoxia (N-EVs) and hypoxia (H-EVs) and observed that changing the O2 status led to variations in the selective loading of miRNAs in the EVs. In silico analysis showed that among the targets of differentially loaded miRNAs, there are transcripts involved in pathways related to cell growth and survival, such as FoxO and HIF-1 pathways. The data obtained reinforce the pro-regenerative potential of EVs obtained from E-CD133 cells and shows that fine tuning of their properties may be regulated by culture conditions.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Selective Loading and Variations in the miRNA Profile of Extracellular Vesicles from Endothelial-like Cells Cultivated under Normoxia and Hypoxia

Robert

Marcon

Angulski

et al. 2022

IJMS

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“…As summarized in Additional file 2 : Table S2, the EVs from ADSCs and BMSCs exhibited similar characteristics and exerted protective functions in a wide array of diseases like EPC-EVs. Recently, Miyasaki and colleagues compared the efficiency of EVs from mesenchymal stem cells and EPCs in treating chronic kidney disease and found similar improvement in renal function in terms of serum albumin, cystatin C, crystals in the renal tubules, and fibrosis, rather than staining of alpha-smooth muscle actin [ 176 ]. However, the direct comparison between different types of EVs was rare, and further studies are needed.…”

Section: Future Perspectives and Conclusionmentioning

confidence: 99%

Comprehensive insight into endothelial progenitor cell-derived extracellular vesicles as a promising candidate for disease treatment

Chen

et al. 2022

Stem Cell Res Ther

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Endothelial progenitor cells (EPCs), which are a type of stem cell, have been found to have strong angiogenic and tissue repair capabilities. Extracellular vesicles (EVs) contain many effective components, such as cellular proteins, microRNAs, messenger RNAs, and long noncoding RNAs, and can be secreted by different cell types. The functions of EVs depend mainly on their parent cells. Many researchers have conducted functional studies of EPC-derived EVs (EPC-EVs) and showed that they exhibit therapeutic effects on many diseases, such as cardiovascular disease, acute kidney injury, acute lung injury, and sepsis. In this review article, we comprehensively summarized the biogenesis and functions of EPCs and EVs and the potent role of EPC-EVs in the treatment of various diseases. Furthermore, the current problems and future prospects have been discussed, and further studies are needed to compare the therapeutic effects of EVs derived from various stem cells, which will contribute to the accelerated translation of these applications in a clinical setting.

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“…However, under pathological conditions, the NFs can stimulate inflammation, fibrosis, coagulation, and oncogenesis. Recently, both in vivo and in vitro studies have shown explosive advances regarding the protective role of NFs in various renal diseases [8,[15][16][17][18].…”

mentioning

confidence: 99%

Morphological pattern of kidneys in rats with infravesical urinary obstruction following administration of biologically active compositions containing neurotrophic factors

Globa

Божок

Legach

et al. 2022

Ukr. J. Nephrol. and Dial.

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Abstract. The research aimed to study the morphological characteristics of kidneys after intraperitoneal administration of biologically active compositions (BACs) in rats with infravesical obstruction (IVO). Methods. IVO was reproduced by surgical ligation. BACs were injected intraperitoneally for 10 days. The morphometric parameters of the kidneys were determined by examining their structure (the areas of renal corpuscle, glomerulus, the cavity of the glomerular capsule, outer and inner diameters of the tubules, the tubular index, the outer diameter and area of the vascular lumen). The experimental animals were divided into the following groups: Group 1 was saved as an intact control group, Group 2 received “Cortexin”, Group 3 was given CMCNMG, Group 4 received BCM, and Group 5 was not treated (U). Results. BACs obtained from a culture of native mantle gliocytes (MG) and BCM were involved in the remodeling of the kidneys’ structure being changed during IVO. The renal corpuscle area was found to be increased in groups 2, 4, and 5 by 42.3%, 193.9%, and 72.3%, respectively, compared with the control group. At the same time, the extent of renal corpuscle hypertrophy in group 3 was minimal and approached the control values. The glomerulus area expanded by 35.4%, 181.1%, and 34% in animals of groups 3, 4, and 5, respectively, compared with the control group. However, the difference in the index between group 5 and BAC-treated animals was not significant, except for group 4. The Bowman's capsule area increased by 117.6%, 235.8%, and 186%, in groups 2, 4 and 5, respectively, compared with the control group. Interestingly, the values in groups 1 and 3 were in agreement but differed from group 5. The lowest values of outer and inner diameters of renal tubules were determined in group 3, which were close to those in the control group but significantly different from those of other groups. An increased tubular index (by 1.35 and 1.4 times) was revealed in groups 3 and 4, compared with other groups. The lowest values were found in groups 2 and 5. The maximum values of the average diameter and area of the vessel lumen were determined in groups 3 and 4, and the minimum values were obtained in group 5. It is noteworthy that the indices of these groups were significantly different from those of group 5. Conclusions. The research results suggest that the phenomena of glomerulosclerosis, tubular atrophy, and renal interstitial fibrosis in rats can be alleviated, as well as the morphological structure of rat kidneys can be partially restored against the background of IVO after administration of CMCNMG and, to a lesser extent, BCM due to the multidirectional action of neurotrophic factors.

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Treatment of Chronic Kidney Disease with Extracellular Vesicles from Mesenchymal Stem Cells and CD133+ Expanded Cells: A Comparative Preclinical Analysis

Cited by 12 publications

References 86 publications

Selective Loading and Variations in the miRNA Profile of Extracellular Vesicles from Endothelial-like Cells Cultivated under Normoxia and Hypoxia

Selective Loading and Variations in the miRNA Profile of Extracellular Vesicles from Endothelial-like Cells Cultivated under Normoxia and Hypoxia

Comprehensive insight into endothelial progenitor cell-derived extracellular vesicles as a promising candidate for disease treatment

Morphological pattern of kidneys in rats with infravesical urinary obstruction following administration of biologically active compositions containing neurotrophic factors

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