Intraperitoneal injection of MSC-derived exosomes prevent experimental bronchopulmonary dysplasia

Braun, Ruedi K.; Chetty, Chandramu; Balasubramaniam, Vivek; Centanni, Ryan; Haraldsdóttir, Kristín; Hematti, Peiman; Eldridge, Marlowe W.

doi:10.1016/j.bbrc.2018.08.019

Cited by 92 publications

(62 citation statements)

References 31 publications

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“…Of interest, an isolated case study involving a 10-month-old female BPD patient with superimposed acute respiratory distress syndrome found that a single dose of MSCs was associated with dramatic reduction in lung fibrosis assessed by computed tomographic scan imaging of the chest and pronounced clinical improvement of lung function [38]. Our findings are also in agreement with previous studies that have shown beneficial effects following "early" MEx interventions in experimental BPD [18][19][20][21], and recent preclinical data that demonstrated treatment of the adult rat BPD lung with MSCs improved lung injury when administered in multiple doses or at an early stage of adulthood [39]. In accordance, previous studies have demonstrated that the MSC secretome (MSC-CM) is able to partially revert core features of neonatal murine BPD [15,16].…”

Section: Discussionsupporting

confidence: 90%

Mesenchymal stromal cell‐derived small extracellular vesicles restore lung architecture and improve exercise capacity in a model of neonatal hyperoxia‐induced lung injury

Willis

Fernandez-Gonzalez

Reis

et al. 2020

J of Extracellular Vesicle

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Early administration of mesenchymal stromal cell (MSC)-derived small extracellular vesicles (MEx) has shown considerable promise in experimental models of bronchopulmonary dysplasia (BPD). However, the ability of MEx to reverse the long-term pulmonary complications associated with established BPD remains unknown. In this study, MEx were isolated from media conditioned by human Wharton's Jelly-derived MSC cultures. Newborn mice (FVB strain) were exposed to hyperoxia (HYRX (75% O2)) before returning to room air at postnatal day 14 (PN14). Following prolonged HYRX-exposure, animals received a single MEx dose at PN18 or serial MEx treatments at PN18-39 ("late" intervention). This group was compared to animals that received an early single MEx dose at PN4 ("early" intervention). Animals were harvested at PN28 or 60 for assessment of pulmonary parameters. We found that early and late MEx interventions effectively ameliorated core features of HYRX-induced neonatal lung injury, improving alveolar simplification, pulmonary fibrosis, vascular remodelling and blood vessel loss. Exercise capacity testing and assessment of pulmonary hypertension (PH) showed functional improvements following both early and late MEx interventions. In conclusion, delivery of MEx following prolonged HYRX-exposure improves core features of experimental BPD, restoring lung architecture, decreasing pulmonary fibrosis and vascular muscularization, ameliorating PH and improving exercise capacity. Taken together, delivery of MEx may not only be effective in the immediate neonatal period to prevent the development of BPD but may provide beneficial effects for the management and potentially the reversal of cardiorespiratory complications in infants and children with established BPD.

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Section: Discussionsupporting

confidence: 90%

Mesenchymal stromal cell‐derived small extracellular vesicles restore lung architecture and improve exercise capacity in a model of neonatal hyperoxia‐induced lung injury

Willis

Fernandez-Gonzalez

Reis

et al. 2020

J of Extracellular Vesicle

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“…In recent decades, increasing studies have focused on exosomes, a subclass of extracellular vesicles, which were involved in intercellular communication and released by most cell types [28]. Cells can trigger cancer-related disorders after the recognition and uptake of circulating exosomal miRNAs, providing indications for early tumor biopsy, diagnosis, and treatment [29,30]. Here, we demenstrated that serum exosomal miR-122 expressions were tumor-derived and remarkably upregulated in CRC patients with LM.…”

Section: Discussionmentioning

confidence: 68%

Serum exosomal miR-122 as a potential diagnostic and prognostic biomarker of colorectal cancer with liver metastasis

Sun¹,

Liu²,

Pan³

et al. 2020

J. Cancer

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Background: Liver is the most common site for metastatic spread of CRC at the time of diagnosis which leads to high mortality. This study aimed to identify novel circulating exosomal miRNAs as biomarkers of colorectal cancer (CRC) with liver metastasis (LM). Materials and methods: Candidate miRNAs were selected through integrated analysis of Gene Expression Omnibus (GEO) database as well as clinical samples. Exosomes isolated from serum and cultured media were identified by using transmission electron microscopy (TEM) and western blot. The expression levels and diagnostic value of candidate miRNAs were further tested and validated through qRT-PCR and receiver operating characteristic curve (ROC) analysis. The association of candidate miRNA expressions with patients' prognosis was analyzed with logistic regression and Cox proportional hazards regression models. Results: After integrated analysis of three GEO datasets and clinical samples, miR-122 was discovered to be remarkably overexpressed in tissues of CRC patients. Then we revealed that elevated serum miR-122 was tumor-derived by being packaged into exosomes. The expressions of serum exosomal miR-122 were significantly upregulated in CRC patients, especially in those with LM. Serum exosomal miR-122 expressions could differentiate CRC patients with LM from healthy controls and patients without LM with area under the ROC curve (AUC) of 0.89 and 0.81. Uni-and multivariate logistic regression showed that serum exosomal miR-122 was an independent prognostic indicator of CRC patients. Conclusions: Serum exosomal miR-122 was a novel potential diagnostic and prognostic biomarker in CRC patients with LM.

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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%

“…However, the knockdown of TSG-6 in MSC-derived exosomes abolishes the therapeutic effects of the exosomes [74]. Furthermore, Braun et al [88] demonstrated that MSC-derived exosomes in vitro stimulated the extensive capillary network formation of human umbilical vein endothelial cells (HUVECs) in vitro, but this function was diminished by anti-VEGF antibodies. The presence of the VEGF protein has also been revealed in the MSC-derived CM, but not in the exosome-depleted media [88].…”

Section: Msc-derived Secretomes For Bpd Therapymentioning

confidence: 99%

“…Furthermore, Braun et al [88] demonstrated that MSC-derived exosomes in vitro stimulated the extensive capillary network formation of human umbilical vein endothelial cells (HUVECs) in vitro, but this function was diminished by anti-VEGF antibodies. The presence of the VEGF protein has also been revealed in the MSC-derived CM, but not in the exosome-depleted media [88]. Increased comprehension of the MSC-derived secretomes will contribute to the development of new strategies for BPD therapy.…”

Section: Msc-derived Secretomes For Bpd Therapymentioning

confidence: 99%

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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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Intraperitoneal injection of MSC-derived exosomes prevent experimental bronchopulmonary dysplasia

Cited by 92 publications

References 31 publications

Mesenchymal stromal cell‐derived small extracellular vesicles restore lung architecture and improve exercise capacity in a model of neonatal hyperoxia‐induced lung injury

Mesenchymal stromal cell‐derived small extracellular vesicles restore lung architecture and improve exercise capacity in a model of neonatal hyperoxia‐induced lung injury

Serum exosomal miR-122 as a potential diagnostic and prognostic biomarker of colorectal cancer with liver metastasis

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

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