Early gestational mesenchymal stem cell secretome attenuates experimental bronchopulmonary dysplasia in part via exosome-associated factor TSG-6

Chaubey, Sushma; Thueson, Sam; Ponnalagu, Devasena; Alam, Mohammad Afaque; Gheorghe, Ciprian P.; Aghai, Zubair H.; Singh, Harpreet; Bhandari, Vineet

doi:10.1186/s13287-018-0903-4

Cited by 149 publications

(124 citation statements)

References 83 publications

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“…The identification of astroglial activation in pigs supports the capacity of AD-MSCs to reduce GFAP expression predominantly in the caudal direction from the epicenter of injury, similar to what we found in rats although to a lesser degree. The potential reduction in astroglial activation was attributed to the ability of MSCs to decrease cyclooxygenase-2 and IL-6 cytokine levels [18,59] and secretion of TNF-stimulated gene-6 [69][70][71][72], which consequently decreases NF-κB signaling, resulting in modulation of A1 neuroinflammatory reactive astrocytes [73,74]. We found no effect of AD-MSCs treatment on microglial activation in pigs, similar to results in rats.…”

Section: Discussionsupporting

confidence: 74%

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

et al. 2019

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Here, we provide a first comparative study of the therapeutic potential of allogeneic mesenchymal stem cells derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and dental pulp (DP-MSCs) embedded in fibrin matrix, in small (rat) and large (pig) spinal cord injury (SCI) models during subacute period of spinal contusion. Results of behavioral, electrophysiological, and histological assessment as well as immunohistochemistry and real-time polymerase chain reaction analysis suggest that application of AD-MSCs combined with a fibrin matrix within the subacute period in rats (2 weeks after injury), provides significantly higher post-traumatic regeneration compared to a similar application of BM-MSCs or DP-MSCs. Within the rat model, use of AD-MSCs resulted in a marked change in: (1) restoration of locomotor activity and conduction along spinal axons; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of microglial and astroglial activation. The effect of an autologous application of AD-MSCs during the subacute period after spinal contusion was also confirmed in pigs (6 weeks after injury). Effects included: (1) partial restoration of the somatosensory spinal pathways; (2) reduction of post-traumatic cavitation and enhancing tissue retention; and (3) modulation of astroglial activation in dorsal root entry zone. However, pigs only partially replicated the findings observed in rats. Together, these results indicate application of AD-MSCs embedded in fibrin matrix at the site of SCI during the subacute period can facilitate regeneration of nervous tissue in rats and pigs. These results, for the first time, provide robust support for the use of AD-MSC to treat subacute SCI.

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Section: Discussionsupporting

confidence: 74%

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

et al. 2019

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“…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. Interestingly, another study demonstrated the repair effect of MSC-derived exosomes in a BPD animal model [74]. MSC-derived exosomes can repair the lung injury and improve BPD-associated brain injury as revealed by decreased brain cell death and reversed hypomyelination.…”

Section: Msc-derived Secretomes For Bpd Therapymentioning

confidence: 99%

“…Yan et al demonstrated that human umbilical cord MSC (hUC-MSC) exosomes promoted hepatocyte recovery from oxidative stress via the antioxidant and antiapoptotic effects of exosomal glutathione peroxidase1 (GPX1) both in vitro and in vivo, however, GPX1 knockdown was found to delay this hepatoprotective effect [72]. MSC exosomes have also been reported to mediate several known functions of MSCs in premature infant diseases, including modulating inflammatory/immune responses and reducing fibrosis, apoptosis, and oxidative stress [73][74][75][76]. However, more in-depth research is required to explore the mechanisms underlying the effects of exosomes.…”

Section: Msc-derived Evs: a Therapeutic Vector Of Mscs?mentioning

confidence: 99%

“…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%

“…TSG-6 has also been detected in MSC-derived exosome fractions and can decrease the pro-inflammatory cytokines, IL-6, TNF-α, and IL-1β; it can also decrease cell death in lungs and reverse BPD-associated cardiac and brain pathologies in BPD mouse models. 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.…”

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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TSG6‐Exo@CS/GP Attenuates Endometrium Fibrosis by Inhibiting Macrophage Activation in a Murine IUA Model

Sun,

Dong,

et al. 2024

Advanced Materials

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Intrauterine adhesion (IUA), commonly known as Asherman's syndrome, is a disease characterized by the formation of fibrous scar tissue within the uterine cavity, which can lead to severe clinical complications and significantly compromise the reproductive health and fertility of women. Unfortunately, severe cases of IUA currently lack effective treatment. This study presents a novel approach that utilizes TSG6‐modified exosomes (Exos) in conjunction with an injectable thermosensitive hydrogel (CS/GP) to mitigate the occurrence of IUA by reducing endometrium fibrosis in a mouse IUA model. The findings of this study demonstrate that TSG6‐modified Exos effectively inhibit the activation of inflammatory M1‐like macrophages during the initial stages of inflammation and maintains the balance of macrophage phenotypes (M1/M2) during the repair phase. Moreover, TSG6 inhnibits the interaction between macrophages and endometrial stromal fibroblasts, thereby preventing the activation of stromal fibroblasts into myofibroblasts. Furthermore, our research indicates that CS/GP facilitates the sustained release of TSG6‐modified Exos, leading to a significant reduction in both the manifestations of IUA and the extent of endometrium fibrosis. Collectively, through the successful construction of CS/GP loaded with TSG6‐modified Exos, we have achieved a reduction in the occurrence and progression of IUA by mitigating endometrium fibrosis. Consequently, this approach holds promise for the treatment of IUA.This article is protected by copyright. All rights reserved

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Early gestational mesenchymal stem cell secretome attenuates experimental bronchopulmonary dysplasia in part via exosome-associated factor TSG-6

Cited by 149 publications

References 83 publications

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

Mesenchymal Stem Cell Therapy for Spinal Cord Contusion: A Comparative Study on Small and Large Animal Models

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

TSG6‐Exo@CS/GP Attenuates Endometrium Fibrosis by Inhibiting Macrophage Activation in a Murine IUA Model

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