Mesenchymal Stromal Cell‐derived Extracellular Vesicles in Preclinical Animal Models of Tumor Growth: Systematic Review and Meta‐analysis

Bailey, Adrian; Tieu, Alvin; Gupta, Manika; Slobodian, Mitchell; Shorr, Risa; Ramsay, Tim; Rodriguez, R; Fergusson, Dean; Lalu, Manoj M; Allan, David S.

doi:10.1007/s12015-021-10163-5

Cited by 9 publications

(4 citation statements)

References 69 publications

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“…Next, data generated from studies with a low risk of bias may serve as a more accurate indicator for the efficacy of MSC-EVs. Unfortunately, most studies included in our analysis demonstrated an "unclear" risk across a majority of design parameters, which is commonly observed in many fields of preclinical in vivo research (Avey et al, 2016;Bailey et al, 2021aBailey et al, , 2021bBegley & Ioannidis, 2015;Fergusson et al, 2019aFergusson et al, , 2019b. Future analyses will provide greater insights once researchers and journals adopt more complete reporting of preclinical study design (Collins & Tabak, 2014;Henderson et al, 2013;Landis et al, 2012).…”

Section:  Discussionmentioning

confidence: 89%

Mesenchymal stromal cell extracellular vesicles as therapy for acute and chronic respiratory diseases: A meta‐analysis

Tieu

Gnyra

et al. 2021

J of Extracellular Vesicle

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Preclinical studies suggest mesenchymal stromal cell extracellular vesicles (MSC‐EVs) reduce inflammation and improve organ function in lung diseases; however, an objective analysis of all available data is needed prior to translation. Using rigorous meta‐research methods, we determined the effectiveness of MSC‐EVs for preclinical respiratory diseases and identified experimental conditions that may further refine this therapy. A systematic search of MEDLINE/Embase identified 1167 records. After screening, 52 articles were included for data extraction and evaluated for risk of bias and quality of reporting in study design. A random effects meta‐analysis was conducted for acute lung injury (ALI; N = 23), bronchopulmonary dysplasia (BPD; N = 8) and pulmonary arterial hypertension (PAH; N = 7). Subgroup analyses identified EV methods/characteristics that may be associated with improved efficacy. Data is presented as standardized mean differences (SMD) or risk ratios (RR) with 95% confidence intervals (CI). For ALI, MSC‐EVs markedly reduced lung injury (SMD ‐4.33, CI ‐5.73 to ‐2.92), vascular permeability (SMD ‐2.43, CI ‐3.05 to ‐1.82), and mortality (RR 0.39, CI 0.22 to 0.68). Small EVs were more consistently effective than large EVs whereas no differences were observed between tissue sources, immunocompatibility or isolation techniques. For BPD, alveolarization was improved by MSC‐EVs (SMD ‐1.45, CI ‐2.08 to ‐0.82) with small EVs more consistently beneficial then small/large EVs. In PAH, right ventricular systolic pressure (SMD ‐4.16, CI ‐5.68 to ‐2.64) and hypertrophy (SMD ‐2.80, CI ‐3.68 to ‐1.91) were significantly attenuated by EVs. In BPD and PAH, EVs isolated by ultracentrifugation demonstrated therapeutic benefit whereas tangential flow filtration (N = 2) displayed minimal efficacy. Lastly, risk of bias and quality of reporting for experimental design were consistently unclear across all studies. Our findings demonstrate clear potential of MSC‐EVs to be developed as therapy for acute and chronic lung diseases. However, greater transparency in research design and direct comparisons of isolation technique and EV subtypes are needed to generate robust evidence to guide clinical translation. Protocol Registration : PROSPERO CRD42020145334

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Section:  Discussionmentioning

confidence: 89%

Mesenchymal stromal cell extracellular vesicles as therapy for acute and chronic respiratory diseases: A meta‐analysis

Tieu

Gnyra

et al. 2021

J of Extracellular Vesicle

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“…Overall, these data provided strong evidence that engineered hUCMSC-EVs delivering miR-30c-5p could effectively inhibit PELI1 expression and tumor progression in PTC, which partly promoted the clinical transformation of miR-30c-5p-PELI1 axis in tumor treatment. More importantly, in present study, we first investigated the effects of naïve hUCMSC-EVs on PTC progression, as MSC-EVs might exert various effects on cancer cell [32]. We found hUCMSC-EVs significantly decreased PTC cell proliferation and migration in vitro and inhibited tumor growth in vivo.…”

Section: Discussionmentioning

confidence: 93%

“…7C-E, the volume and weight of the tumor treated with miR-30c-5p-EVs was remarkably decreased compared with the NC-EV group. In view of the fact that MSC-EVs exert various effects on cancer cell [32], we then investigated the effect of naïve hUCMSC-EVs on PTC carcinogenesis, and found that compared with treatment with PBS (Control group), treatment of PTC cells with hUCMSC-EVs resulted in a dramatic reduction in proliferation and migration in vitro (Fig. 7A and B) and tumor volume and weight in vivo (Fig.…”

Section: Evs Derived From Mir-30c-5p-modified Hucmsc (Mir-30c-5p-evs) Can Effectively Inhibit Peli1 Expression and Suppress Ptc Progressimentioning

confidence: 99%

MiR-30c-5p loss-induced PELI1 accumulation regulates cell proliferation and migration via activating PI3K/AKT pathway in papillary thyroid carcinoma

Zheng

Zhou²,

et al. 2022

J Transl Med

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Background The aberrant expression of E3 ubiquitin ligase Pellino-1 (PELI1) contributes to several human cancer development and progression. However, its expression patterns and functional importance in papillary thyroid cancer (PTC) remains unknown. Methods PELI1 expression profiles in PTC tissues were obtained and analyzed through the starBase v3.0 analysis. Real-time PCR, Immunohistochemical assays (IHC) and Western blot were used to investigate the mRNA and protein levels of PELI1 in PTC. The effects of PELI1 on PTC cell progression were evaluated through CCK-8, colony formation, Transwell, and Wound healing assay in vitro, and a PTC xenograft mouse model in vivo. The downstream target signal of PELI1 in PTC was analyzed by using Kyoto encyclopedia of genes and genomes (KEGG), and bioinformatics tools were used to identify potential miRNAs targeting PELI1. Human umbilical cord mesenchymal stem cells were modified by miR-30c-5p and the miR-30c-5p containing extracellular vesicles were collected (miR-30c-5p-EVs) by ultra-high-speed centrifugation method. Then, the effects of miR-30c-5p-EVs on PELI1 expression and PTC progression were evaluated both in vitro and in vivo. Results Both mRNA and protein expression of PELI1 were widely increased in PTC tissues, and overexpression of PELI1 was positively correlated with bigger tumor size and lymph node metastases. PELI1 promoted PTC cell proliferation and migration in vitro. While, PELI1 silencing significantly suppressed PTC growth in vivo accompanied with reduced expression of Ki-67 and matrix metallopeptidase 2 (MMP-2). Mechanistically, PI3K-AKT pathway was identified as the downstream target of PELI1, and mediated the functional influence of PELI1 in PTC cells. Moreover, we found that the expression of miR-30c-5p was inversely correlated with PELI1 in PTC samples and further confirmed that miR-30c-5p was a tumor-suppressive miRNA that directly targeted PELI1 to inhibit PTC cell proliferation and migration. Furthermore, we showed that miR-30c-5p-EVs could effectively downregulate PELI1 expression and suppress the PTC cell growth in vitro and in vivo. Conclusion This study not only supported the first evidence that miR-30c-5p loss-induced PELI1 accumulation facilitated cell proliferation and migration by activating the PI3K-AKT pathway in PTC but also provided novel insights into PTC therapy based on miR-carrying-hUCMSC-EVs.

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“…According to one of the latest meta-analyses, MSC-EVs had a mixed response to tumor progression. However, significant suppression of tumor growth was observed frequently with vesicles from MSCs that overexpressed anti-tumor RNA [ 136 ]. Finally, the efficiency of antitumor therapy can be increased by using exosomes derived from osteogenic differentiating MSCs, which induce osteogenic differentiation of cancer stem cells and reprogram them into non-tumor cells [ 137 ].…”

Section: Ev-mediated Intercellular Interactions In Stem Cell Biology ...mentioning

confidence: 99%

Non-Classical Intercellular Communications: Basic Mechanisms and Roles in Biology and Medicine

Polyakova

Калашникова

Belyavsky

2023

IJMS

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In multicellular organisms, interactions between cells and intercellular communications form the very basis of the organism’s survival, the functioning of its systems, the maintenance of homeostasis and adequate response to the environment. The accumulated experimental data point to the particular importance of intercellular communications in determining the fate of cells, as well as their differentiation and plasticity. For a long time, it was believed that the properties and behavior of cells were primarily governed by the interactions of secreted or membrane-bound ligands with corresponding receptors, as well as direct intercellular adhesion contacts. In this review, we describe various types of other, non-classical intercellular interactions and communications that have recently come into the limelight—in particular, the broad repertoire of extracellular vesicles and membrane protrusions. These communications are mediated by large macromolecular structural and functional ensembles, and we explore here the mechanisms underlying their formation and present current data that reveal their roles in multiple biological processes. The effects mediated by these new types of intercellular communications in normal and pathological states, as well as therapeutic applications, are also discussed. The in-depth study of novel intercellular interaction mechanisms is required for the establishment of effective approaches for the control and modification of cell properties both for basic research and the development of radically new therapeutic strategies.

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Mesenchymal Stromal Cell‐derived Extracellular Vesicles in Preclinical Animal Models of Tumor Growth: Systematic Review and Meta‐analysis

Cited by 9 publications

References 69 publications

Mesenchymal stromal cell extracellular vesicles as therapy for acute and chronic respiratory diseases: A meta‐analysis

Mesenchymal stromal cell extracellular vesicles as therapy for acute and chronic respiratory diseases: A meta‐analysis

MiR-30c-5p loss-induced PELI1 accumulation regulates cell proliferation and migration via activating PI3K/AKT pathway in papillary thyroid carcinoma

Non-Classical Intercellular Communications: Basic Mechanisms and Roles in Biology and Medicine

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