Intratracheal administration of clinical-grade mesenchymal stem cell-derived extracellular vesicles reduces lung injury in a rat model of bronchopulmonary dysplasia

Porzionato, Andrea; Zaramella, Patrizia; Dedja, Arben; Guidolin, Diego; Wemmel, Kelly Van; Macchi, Veronica; Jurga, Marcin; Perilongo, Giorgio; De, Raffaele; Baraldi, Eugenio; Muraca, Maurizio

doi:10.1152/ajplung.00109.2018

Cited by 98 publications

(88 citation statements)

References 68 publications

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“…The composition of exosomes can be therapeutically effective, in which they give a synergistic effect when they are used as nanocarriers. It was reported that the intratracheal administration of EVs, such as exosomes that are originated from mesenchymal stem cells (MSCs), can be an effective treatment for bronchopulmonary dysplasia (BPD) in an animal model [222]. In their study, the number of alveoli in the BPD animal model was significantly increased when these EVs were administrated intratracheally.…”

Section: Nanocarriers For Cf Treatmentmentioning

confidence: 99%

Cystic Fibrosis: Overview of the Current Development Trends and Innovative Therapeutic Strategies

et al. 2020

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Cystic Fibrosis (CF), an autosomal recessive genetic disease, is caused by a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). This mutation reduces the release of chloride ions (Cl−) in epithelial tissues, and hyperactivates the epithelial sodium channels (ENaC) which aid in the absorption of sodium ions (Na+). Consequently, the mucus becomes dehydrated and thickened, making it a suitable medium for microbial growth. CF causes several chronic lung complications like thickened mucus, bacterial infection and inflammation, progressive loss of lung function, and ultimately, death. Until recently, the standard of clinical care in CF treatment had focused on preventing and treating the disease complications. In this review, we have summarized the current knowledge on CF pathogenesis and provided an outlook on the current therapeutic approaches relevant to CF (i.e., CFTR modulators and ENaC inhibitors). The enormous potential in targeting bacterial biofilms using antibiofilm peptides, and the innovative therapeutic strategies in using the CRISPR/Cas approach as a gene-editing tool to repair the CFTR mutation have been reviewed. Finally, we have discussed the wide range of drug delivery systems available, particularly non-viral vectors, and the optimal properties of nanocarriers which are essential for successful drug delivery to the lungs.

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Section: Nanocarriers For Cf Treatmentmentioning

confidence: 99%

Cystic Fibrosis: Overview of the Current Development Trends and Innovative Therapeutic Strategies

et al. 2020

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“…Chaubey et al demonstrated in a neonatal murine BPD model that umbilical cord MSC-derived EVs reduced pulmonary inflammation, pulmonary hypertension, and right ventricular hypertension partially mediated through the exosomal protein tumor necrosis factor alpha-stimulated gene-6 (TSG-6) [39]. In another report, umbilical cord MSC-derived EVs were as effective as the parental MSCs in protecting against hypoxia-induced lung injury in neonatal rats [40]. These beneficial effects were partially attenuated by knocking down the vascular endothelial growth factor (VEGF) gene in MSCs prior to EV isolation.…”

Section: Bronchopulmonary Dysplasiamentioning

confidence: 99%

Therapeutic Use of Extracellular Vesicles for Acute and Chronic Lung Disease

Worthington

Hagood

2020

IJMS

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Multipotent mesenchymal stem cells (MSCs) possess regenerative properties and have been shown to improve outcomes and survival in acute and chronic lung diseases, but there have been some safety concerns raised related to MSC-based therapy. Subsequent studies have demonstrated that many of the regenerative effects of MSCs can be attributed to the MSC-derived secretome, which contains soluble factors and extracellular vesicles (EVs). MSC-derived extracellular vesicles (MSC-derived EVs) replicate many of the beneficial effects of MSCs and contain a variety of bioactive factors that are transferred to recipient cells, mediating downstream signaling. MSC-derived EV therapy holds promise as a safe and effective treatment for pulmonary disease, but there remain many scientific and clinical questions that will need to be addressed before EVs are widely applied as a therapy. To date, the use of MSC-derived EVs as a treatment for lung disease has been conducted primarily in in vitro or pre-clinical animal models. In this review, we will discuss the current published research investigating the use of EVs as a potential therapeutic for acute lung injury/acute respiratory distress syndrome (ALI/ARDS), bronchopulmonary dysplasia (BPD), idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), asthma, and silicosis.

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“…Several studies have indicated that soluble factors, such as macrophage colony-stimulating factor 1, osteopontin [86], and STC1 [54], may be principally responsible for the therapeutic abilities of MSC-derived CM. MSC-derived EV [87] and exosome [73,74,88] treatments also block inflammation and reduce fibrosis and pulmonary vascular remodeling, resulting in improved lung function and the amelioration of pulmonary hypertension in hyperoxia-induced BPD. Willis et al [73] showed that MSC-derived exosomes modulated the lung macrophage phenotype by suppressing the pro-inflammatory 'M1' state and enhancing an anti-inflammatory 'M2-like' state both in vitro and in vivo.…”

Section: Msc-derived Secretomes For Bpd Therapymentioning

confidence: 99%

Mesenchymal stem cell-derived secretomes for therapeutic potential of premature infant diseases

et al. 2020

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Preterm birth is a complex syndrome and remains a substantial public health problem globally. Its common complications include periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). Despite great advances in the comprehension of the pathogenesis and improvements in neonatal intensive care and associated medicine, preterm birth-related diseases remain essentially without adequate treatment and can lead to high morbidity and mortality. The therapeutic potential of mesenchymal stem/stromal cells (MSCs) appears promising as evidenced by their efficacy in preclinical models of pathologies relevant to premature infant complications. MSC-based therapeutic efficacy is closely associated with MSC secretomes and a subsequent paracrine action response to tissue injuries, which are complex and abundant in response to the local microenvironment. In the current review, we summarize the paracrine mechanisms of MSC secretomes underlying diverse preterm birth-related diseases, including PVL, BPD, NEC and ROP, are summarized, and focus is placed on MSC-conditioned media (CM) and MSC-derived extracellular vesicles (EVs) as key mediators of modulatory action, thereby providing new insights for future therapies in newborn medicine.lung function and help to remove the ventilator as soon as possible [12]. However, many studies have reported that glucocorticoid can increase the risk of adverse reactions, such as those by the nervous system, in the early or late stages, and its dose and course of treatment are not certain [13,14]. In terms of surgical treatment, preterm infants with surgical NEC are at risk of significant growth reduction and neurodevelopmental impairment (NDI), including cerebral palsy, deafness and blindness [15,16]. These sequelae and complications of prematurity-related diseases affect not only the neonatal period, but also infancy and childhood, and even adolescence and adulthood [17][18][19]. Currently, although various treatment methods have been found to achieve certain curative effects, there still exist several side effects and disputes above. Thus, it is necessary to explore and develop new therapies for the treatment and prevention of premature infant diseases.Accumulating studies have established the importance and feasibility of stem cell-based therapies to ameliorate many degenerative and inflammatory diseases. Among these stem/progenitor cell types, mesenchymal stem/stromal cells (MSCs) have received more extensive attention because they are easily extracted, exert anti-inflammatory effects, have low immunogenicity and can renew themselves. The therapeutic potential of MSCs has been demonstrated in many diseases such as cancer [20,21] and cardiovascular [22,23] and lung [24][25][26] diseases. MSCs also represent a promising and growing approach to the targeting of various pathological processes and cellular impairments underlying the major abnormalities in premature infant and preterm-associated neonatal diseases [27][28]...

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Intratracheal administration of clinical-grade mesenchymal stem cell-derived extracellular vesicles reduces lung injury in a rat model of bronchopulmonary dysplasia

Cited by 98 publications

References 68 publications

Cystic Fibrosis: Overview of the Current Development Trends and Innovative Therapeutic Strategies

Cystic Fibrosis: Overview of the Current Development Trends and Innovative Therapeutic Strategies

Therapeutic Use of Extracellular Vesicles for Acute and Chronic Lung Disease

Mesenchymal stem cell-derived secretomes for therapeutic potential of premature infant diseases

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