Human Amnion Epithelial Cells Repair Established Lung Injury

Vosdoganes, Patricia; Wallace, Euan M.; Chan, Sze Wah Samuel; Acharya, Rutu; Moss, Timothy; Lim, Rebecca

doi:10.3727/096368912x657657

Cited by 58 publications

(63 citation statements)

References 46 publications

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“…Administration of hAECs to mice modulates the immune response to decrease long-term fibrosis and BPD-like lung injury [16, 43, 44] and can repair established lung injury [45]. Our study provides evidence for a role of hAECs in reducing lung tissue injury through acute modulation of local inflammatory responses.…”

Section: Discussionmentioning

confidence: 79%

Human amnion epithelial cells modulate the inflammatory response to ventilation in preterm lambs

et al. 2017

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Ventilation of preterm neonates causes pulmonary inflammation that can contribute to lung injury, propagate systemically and result in long-term disease. Modulation of this initial response may reduce lung injury and its sequelae. We aimed to determine the effect of human amnion epithelial cells (hAECs) on immune activation and lung injury in preterm neonatal lambs. Preterm lambs received intratracheal hAECs (90x106) or vehicle, prior to 2 h of mechanical ventilation. Within 5 min of ventilation onset, lambs also received intravenous hAECs (90x106) or vehicle. Lung histology, bronchoalveolar lavage (BAL) cell phenotypes, and cytokine profiles were examined after 2 h of ventilation, and in unventilated controls. Histological indices of lung injury were higher than control, in vehicle-treated ventilated lambs but not in hAEC-treated ventilated lambs. Ventilation-induced pulmonary leukocyte recruitment was greater in hAEC-treated lambs than in vehicle-treated lambs. Lung IL-1β and IL-6 mRNA expression was higher in vehicle- and hAEC-treated ventilated lambs than in controls but IL-8 mRNA levels were greater than control only in vehicle-treated ventilated lambs. Numbers of CD44+ and CD21+ lymphocytes and macrophages from the lungs were altered in vehicle- and hAEC-treated ventilated lambs. Numbers of CD8+ macrophages were lower in hAEC-treated ventilated lambs than in vehicle-treated ventilated lambs. Indices of systemic inflammation were not different between vehicle- and hAEC-treated lambs. Human amnion epithelial cells modulate the pulmonary inflammatory response to ventilation in preterm lambs, and reduce acute lung injury. Immunomodulatory effects of hAECs reduce lung injury in preterm neonates and may protect against longer-term respiratory disease.

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Section: Discussionmentioning

confidence: 79%

Human amnion epithelial cells modulate the inflammatory response to ventilation in preterm lambs

et al. 2017

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“…In a rat model of cigarette smoke inhalation induced obstructive lung disease, intra‐tracheal instillation of hAEC delayed the progression of emphysema and alleviated lung damage by reducing systemic and pulmonary levels of pro‐inflammatory cytokine, IL‐8 . A recent study in an ovalbumin induced chronic allergic airway disease model showed that hAEC were superior to bone marrow derived MSC in their ability to diminish ovalbumin induced fibrosis and airway hyper‐responsiveness . Similarly, hAEC reportedly exerted immunomodulatory effects in the developing lungs such that delivery of hAECs attenuated pulmonary inflammation in sheep fetuses that were challenged with lipopolysaccharide .…”

Section: Preclinical Applicationsmentioning

confidence: 99%

Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog?

Lim

2017

Stem Cells Translational Medicine

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The clinical application of the fetal membranes dates back to nearly a century. Their use has ranged from superficial skin dressings to surgical wound closure. The applications of the fetal membranes are constantly evolving, and key to this is the uncovering of multiple populations of stem and stem‐like cells, each with unique properties that can be exploited for regenerative medicine. In addition to pro‐angiogenic and immunomodulatory properties of the stem and stem‐like cells arising from the fetal membranes, the dehydrated and/or decellularized forms of the fetal membranes have been used to support the growth and function of other cells and tissues, including adipose‐derived mesenchymal stem cells. This concise review explores the biological origin of the fetal membranes, a history of their use in medicine, and recent developments in the use of fetal membranes and their derived stem and stem‐like cells in regenerative medicine. Stem Cells Translational Medicine 2017;6:1767–1776

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“…hAECs were most beneficial at day 14 and not when administered earlier at day 7, during a time of peak inflammation. This likely reflects the evolution of the immune and inflammatory environment post-insult and that hAECs are not only capable of preventing injury but are also capable of repair once the injury is already established (Vosdoganes et al, 2012). Further studies in models of adult lung disease have demonstrated that the actions of hAECs were independent of tissue engraftment and, most likely, were due to factors released by hAECs rather than through direct effects of the hAECs themselves (Tan et al, 2013).…”

Section: Perinatal Hypoxic-ischemic Brain Injury and Haecsmentioning

confidence: 99%

Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells

et al. 2013

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In the research, clinical, and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however, this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical, and logistical considerations, together with the propensity for native cells to form teratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs), or umbilical cord blood (UCB) stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs), and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain injury.

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Human Amnion Epithelial Cells Repair Established Lung Injury

Cited by 58 publications

References 46 publications

Human amnion epithelial cells modulate the inflammatory response to ventilation in preterm lambs

Human amnion epithelial cells modulate the inflammatory response to ventilation in preterm lambs

Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog?

Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells

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