Extracellular vesicles influence the pulmonary arterial extracellular matrix in congenital diaphragmatic hernia

Monroe, Madeline N.; Zhaorigetu, Siqin; Gupta, Vikas; Jin, Dong-Yan; Givan, Katelyn D.; Curylo, Alexander L.; Olson, Scott D.; Cox, Charles S.; Segura, Ana; Buja, L. M.; Grande‐Allen, K. Jane; Harting, Matthew T.

doi:10.1002/ppul.24914

Cited by 15 publications

(12 citation statements)

References 30 publications

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“…Our systematic searches yielded a total of 1167 records (Figure 1 ). Following level 1 screening of titles and abstracts, 434 articles underwent level 2 full‐text screening which resulted in a total of 52 studies included for our systematic review (Ahn et al., 2018 ; Aliotta et al., 2017 , 2016 ; Bandeira et al., 2018 ; Braun et al., 2018 ; Chaubey et al., 2018 ; Chen et al., 2014 , 2019 , 2020 ; Choi et al., 2014 ; Cruz et al., 2015 ; de Castro et al., 2017 ; Deng et al., 2020 ; Dinh et al., 2020 ; Fang et al., 2020a , 2020b ; Gao et al., 2020 ; Hao et al., 2019 ; Harrell et al., 2020 ; Hogan et al., 2019 ; Huang et al., 2019 ; Khatri et al., 2018 ; Kim et al., 2020 ; Klinger et al., 2020 ; Lee et al., 2012 ; Lei et al., 2020 ; Li et al., 2015 , 2019a , 2019b , 2020 ; Liu et al., 2018 , 2019a , 2019b ; Mansouri et al., 2019 ; Maremanda et al., 2019 ; Monroe et al., 2020 ; Monsel et al., 2015 ; Porzionato et al., 2019 ; Potter et al., 2018 ; Silva et al., 2019 ; Stone et al., 2017 ; Tang et al., 2017 ; Varkouhi et al., 2019 ; Wang et al., 2020 ; Willis et al., …”

Section: Resultsmentioning

confidence: 99%

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: Resultsmentioning

confidence: 99%

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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“…Monroe et al. showed that EVs derived from bone marrow MSCs have a beneficial effect on the extracellular matrix (ECM) of the pulmonary arteries of rat fetuses with CDH, with attenuation of ECM enzymatic activity, rescue of ECM composition, and restoration of medial wall thickness 74 . Furthermore, Zhaorigetu et al.…”

Section: Ev Effects On Pulmonary Vascular Developmentmentioning

confidence: 99%

Fetal lung regeneration using stem cell‐derived extracellular vesicles: A new frontier for pulmonary hypoplasia secondary to congenital diaphragmatic hernia

et al. 2022

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The poor outcomes of babies with congenital diaphragmatic hernia (CDH) are directly related to pulmonary hypoplasia, a condition characterized by impaired lung development. Although the pathogenesis of pulmonary hypoplasia is not fully elucidated, there is now evidence that CDH patients have missing or dysregulated microRNAs (miRNAs) that regulate lung development. A prenatal therapy that supplements these missing/dysregulated miRNAs could be a strategy to rescue normal lung development. Extracellular vesicles (EVs), also known as exosomes when of small dimensions, are lipid‐bound nanoparticles that can transfer their heterogeneous cargo (proteins, lipids, small RNAs) to target cells to induce biological responses. Herein, we review all studies that show evidence for stem cell‐derived EVs as a regenerative therapy to rescue normal development in CDH fetal lungs. Particularly, we report studies showing that administration of EVs derived from amniotic fluid stem cells (AFSC‐EVs) to models of pulmonary hypoplasia promotes fetal lung growth and maturation via transfer of miRNAs that are known to regulate lung developmental processes. We also describe that stem cell‐derived EVs exert effects on vascular remodeling, thus possibly preventing postnatal pulmonary hypertension. Finally, we discuss future perspectives and challenges to translate this promising stem cell EV‐based therapy to clinical practice.

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“…[95][96][97] Accordingly, the reparative potential of EVs and their influence on cell-ECM interactions has been the subject of research aiming to improve cardiac recovery following MI. 98,99 However, the effects of ECM composition and stiffness on EV secretion are poorly understood. Future work should examine if the myocardial ECM composition influences EV yield and also EV cargo type under ischemic conditions.…”

Section: The Future Of Research On Cell-ecm Interactions and Cardiac Repairmentioning

confidence: 99%

Bidirectional Relationship Between Cardiac Extracellular Matrix and Cardiac Cells in Ischemic Heart Disease

et al. 2021

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Ischemic heart diseases (IHDs), including myocardial infarction and cardiomyopathies, are a leading cause of mortality and morbidity worldwide. Cardiac-derived stem and progenitor cells have shown promise as a therapeutic for IHD but are limited by poor cell survival, limited retention, and rapid washout. One mechanism to address this is to encapsulate the cells in a matrix or three-dimensional construct, so as to provide structural support and better mimic the cells' physiological microenvironment during administration. More specifically, the extracellular matrix (ECM), the native cellular support network, has been a strong candidate for this purpose. Moreover, there is a strong consensus that the ECM and its residing cells, including cardiac stem cells, have a constant interplay in response to tissue development, aging, disease progression, and repair. When externally stimulated, the cells and ECM work together to mutually maintain the local homeostasis by initially altering the ECM composition and stiffness, which in turn alters the cellular response and behavior. Given this constant interplay, understanding the mechanism of bidirectional cell-ECM interaction is essential to develop better cell implantation matrices to enhance cell engraftment and cardiac tissue repair. This review summarizes current understanding in the field, elucidating the signaling mechanisms between cardiac ECM and residing cells in response to IHD onset. Furthermore, this review highlights recent advances in native ECM-mimicking cardiac matrices as a platform for modulating cardiac cell behavior and inducing cardiac repair.

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Extracellular vesicles influence the pulmonary arterial extracellular matrix in congenital diaphragmatic hernia

Cited by 15 publications

References 30 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

Fetal lung regeneration using stem cell‐derived extracellular vesicles: A new frontier for pulmonary hypoplasia secondary to congenital diaphragmatic hernia

Bidirectional Relationship Between Cardiac Extracellular Matrix and Cardiac Cells in Ischemic Heart Disease

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