Human amnion epithelial cells reduce ventilation-induced preterm lung injury in fetal sheep

Hodges, Ryan; Jenkin, Graham; Hooper, Stuart B.; Allison, Beth J.; Lim, Rebecca; Dickinson, Hayley; Miller, Stephanie; Vosdoganes, Patricia; Wallace, Euan M.

doi:10.1016/j.ajog.2012.02.038

Cited by 80 publications

(82 citation statements)

References 33 publications

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“…Moreover, therapeutic efficacy of other cell types, including endothelial progenitor and amniotic epithelial cells, in BPD has also been reported (10,44,45). These findings suggest that the protective mechanisms of MSC transplantation might mainly be related to their ability to stimulate the survival and recovery of damaged tissue by paracrine manners (Figure 1).…”

Section: Paracrine Protectionmentioning

confidence: 81%

Strategies to enhance paracrine potency of transplanted mesenchymal stem cells in intractable neonatal disorders

et al. 2017

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Mesenchymal stem cell (MSC) transplantation represents the next breakthrough in the treatment of currently intractable and devastating neonatal disorders with complex multifactorial etiologies, including bronchopulmonary dysplasia, hypoxic ischemic encephalopathy, and intraventricular hemorrhage. Absent engraftment and direct differentiation of transplanted MSCs, and the "hit-and-run" therapeutic effects of these MSCs suggest that their pleiotropic protection might be attributable to paracrine activity via the secretion of various biologic factors rather than to regenerative activity. The transplanted MSCs, therefore, exert their therapeutic effects not by acting as "stem cells," but rather by acting as "paracrine factors factory." The MSCs sense the microenvironment of the injury site and secrete various paracrine factors that serve several reparative functions, including antiapoptotic, anti-inflammatory, antioxidative, antifibrotic, and/or antibacterial effects in response to environmental cues to enhance regeneration of the damaged tissue. Therefore, the therapeutic efficacy of MSCs might be dependent on their paracrine potency. In this review, we focus on recent investigations that elucidate the specifically regulated paracrine mechanisms of MSCs by injury type and discuss potential strategies to enhance paracrine potency, and thus therapeutic efficacy, of transplanted MSCs, including determining the appropriate source and preconditioning strategy for MSCs and the route and timing of their administration.

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Section: Paracrine Protectionmentioning

confidence: 81%

Strategies to enhance paracrine potency of transplanted mesenchymal stem cells in intractable neonatal disorders

et al. 2017

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“…In experimental models of BPD, EPCs or bone marrow myeloid-like angiogenic cells, and AECs have shown therapeutic potential with restoration of the alveolar structure and vascular integrity in the neonatal hyperoxia mouse model (6, 75). AECs were also reported to have regeneration potential in a fetal sheep model of ventilation-induced lung injury (32). In addition, several reports point to the therapeutic potential of MSCs in models of lung disease, which will be reviewed in the subsequent sections.…”

Section: The Potential Use Of Cell-based Therapies For Developmental mentioning

confidence: 99%

MSC Microvesicles for the Treatment of Lung Disease: A New Paradigm for Cell-Free Therapy

Sdrimas

Kourembanas

2014

Antioxidants & Redox Signaling

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Significance: Bronchopulmonary dysplasia (BPD), also known as chronic lung disease of infancy, is a major complication of preterm birth that, despite improvements in neonatal respiratory support and perinatal care, remains an important cause of morbidity and mortality, often with severe adverse neurodevelopmental sequelae. Even with major advances in our understanding of the pathogenesis of this disease, BPD remains essentially without adequate treatment. Recent Advances: Cell-based therapies arose as a promising treatment for acute and chronic lung injury in many experimental models of disease. Currently, more than 3000 human clinical trials employing cell therapy for the treatment of diverse diseases, including cardiac, neurologic, immune, and respiratory conditions, are ongoing or completed. Among the treatments, mesenchymal stem cells (MSCs) are the most studied and have been extensively tested in experimental models of BPD, pulmonary hypertension, pulmonary fibrosis, and acute lung injury. Critical Issues: Despite the promising potential, MSC therapy for human lung disease still remains at an experimental stage and optimal transplantation conditions need to be determined. Although the mechanism of MSC action can be manifold, accumulating evidence suggests a predominant paracrine, immunomodulatory, and cytoprotective effect. Future Directions: The current review summarizes the effect of MSC treatment in models of lung injury, including BPD, and focuses on the MSC secretome and, specifically, MSC-derived microvesicles as potential key mediators of therapeutic action that can be the focus of future therapies. Antioxid. Redox Signal. 21, 1905Signal. 21, -1915

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“…Fetal lung inflammation induced by intra-amniotic lipopolysaccharide injection is attenuated by hAEC administration [19], and ventilation-induced abnormal lung remodelling in fetal sheep is also reduced [20]. The neuroprotective capacity of hAECs has not been extensively studied; however, hAECs are capable of reducing brain inflammation and injury in preterm fetal sheep exposed to intra-amniotic lipopolysaccharide [21].…”

Section: Introductionmentioning

confidence: 99%

Human Amnion Epithelial Cells Modulate Ventilation-Induced White Matter Pathology in Preterm Lambs

et al. 2015

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Background: Preterm infants can be inadvertently exposed to high tidal volumes (V_T) during resuscitation in the delivery room due to limitations of available equipment. High V_T ventilation of preterm lambs produces cerebral white matter (WM) pathology similar to that observed in preterm infants who develop cerebral palsy. We hypothesized that human amnion epithelial cells (hAECs), which have anti-inflammatory and regenerative properties, would reduce ventilation-induced WM pathology in neonatal late preterm lamb brains. Methods: Two groups of lambs (0.85 gestation) were used, as follows: (1) ventilated lambs (Vent; n = 8) were ventilated using a protocol that induces injury (V_T targeting 15 ml/kg for 15 min, with no positive end-expiratory pressure) and were then maintained for another 105 min, and (2) ventilated + hAECs lambs (Vent+hAECs; n = 7) were similarly ventilated but received intravenous and intratracheal administration of 9 × 10⁷ hAECs (18 × 10⁷ hAECs total) at birth. Oxygenation and ventilation parameters were monitored in real time; cerebral oxygenation was measured using near-infrared spectroscopy. qPCR (quantitative real-time PCR) and immunohistochemistry were used to assess inflammation, vascular leakage and astrogliosis in both the periventricular and subcortical WM of the frontal and parietal lobes. An unventilated control group (UVC; n = 5) was also used for qPCR analysis of gene expression. Two-way repeated measures ANOVA was used to compare physiological data. Student's t test and one-way ANOVA were used for immunohistological and qPCR data comparisons, respectively. Results: Respiratory parameters were not different between groups. Interleukin (IL)-6 mRNA levels in subcortical WM were lower in the Vent+hAECs group than the Vent group (p = 0.028). IL-1β and IL-6 mRNA levels in periventricular WM were higher in the Vent+hAECs group than the Vent group (p = 0.007 and p = 0.001, respectively). The density of Iba-1-positive microglia was lower in the subcortical WM of the parietal lobes (p = 0.010) in the Vent+hAECs group but not in the periventricular WM. The number of vessels in the WM of the parietal lobe exhibiting protein extravasation was lower (p = 0.046) in the Vent+hAECs group. Claudin-1 mRNA levels were higher in the periventricular WM (p = 0.005). The density of GFAP-positive astrocytes was not different between groups. Conclusions: Administration of hAECs at the time of birth alters the effects of injurious ventilation on the preterm neonatal brain. Further studies are required to understand the regional differences in the effects of hAECs on ventilation-induced WM pathology and their net effect on the developing brain.

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Human amnion epithelial cells reduce ventilation-induced preterm lung injury in fetal sheep

Cited by 80 publications

References 33 publications

Strategies to enhance paracrine potency of transplanted mesenchymal stem cells in intractable neonatal disorders

Strategies to enhance paracrine potency of transplanted mesenchymal stem cells in intractable neonatal disorders

MSC Microvesicles for the Treatment of Lung Disease: A New Paradigm for Cell-Free Therapy

Human Amnion Epithelial Cells Modulate Ventilation-Induced White Matter Pathology in Preterm Lambs

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