Abstract
BackgroundIdiopathic pulmonary fibrosis (IPF) urgently requires effective treatment. Bleomycin-induced lung injury models are characterized by initial inflammation and secondary fibrosis, consistent with the pathological features of IPF. Human amniotic epithelial cells (hAECs) exhibit good differentiation potential and paracrine activity and are thus ideal for cell-based clinical therapies. The therapeutic effects of hAECs on lung fibrosis are attributed to many factors. We performed a systematic review of preclinical studies investigating the treatment of pulmonary fibrosis with hAECs to provide suggestions for their clinical use.MethodsPubMed and EMBASE were searched for original studies describing hAEC therapy in animal bleomycin-induced pulmonary fibrosis models. After quality assessments, the number and species of experimental animals, bleomycin dose, hAEC source and dosage, time and route of administration of transplanted cells in animals, and time animals were euthanized in nine controlled preclinical studies were summarized. Ashcroft scores, lung collagen contents, inflammatory cells and cytokines were quantitatively and/or qualitatively analyzed in this review. Publication bias was also assessed.ResultsEach of the nine preclinical studies have unique characteristics regarding hAEC use. Ashcroft scores and lung collagen contents were decreased following hAEC transplantation in bleomycin-injured mice. Histopathology was also improved in most studies following treatment with hAECs. hAECs modulated macrophages, neutrophils, T cells, dendritic cells and the mRNA or protein levels of cytokines associated with inflammatory reactions (tumor necrosis factor-α, transforming growth factor-β, interferon-γ and interleukin) in lung tissues of bleomycin-injured mice.ConclusionshAECs alleviate and reverse the progression of bleomycin-induced lung fibrosis in mice and may represent a new clinical treatment for IPF. hAECs exert anti-inflammatory and anti-fibrotic effects by modulating macrophage, neutrophil, T cell, dendritic cell and related cytokine levels in mice with bleomycin-induced lung fibrosis. Cell generation and the route, source and timing of hAEC transplantation all determine the therapeutic effectiveness of hAECs.
Highlights
Lung injury accompanied by inflammation, cell death and inflammatory cytokine production in response to chemical and/or physical stimuli may result in pulmonary fibrosis
Histopathology was improved in most studies following treatment with Human amniotic epithelial cells (hAECs). hAECs modulated macrophages, neutrophils, T cells, dendritic cells and the mRNA or protein levels of cytokines associated with inflammatory reactions
C57BL/6 mice were used in 7 research studies, while SCID mice and wild-type mice were used in the other two studies. hAECs were transplanted between 24 h and 14 d after treatment with bleomycin
Summary
Lung injury accompanied by inflammation, cell death and inflammatory cytokine production in response to chemical and/or physical stimuli may result in pulmonary fibrosis. The bleomycin-induced model of lung injury is consistent with the developmental process of IPF and is a well-characterized model of the initial inflammation and subsequent fibrosis [2]. These animal models are suitable and convenient for preclinical studies of these diseases. HAECs are advantageous because they are retrieved non-invasively from a rich source and exert paracrine functions, similar to MSCs. Most importantly, hAECs differentiate into alveolar epithelial cells both in vitro and in mice in vivo, representing an ideal cell-based clinical therapeutic option for lung regeneration [4,5]. We performed a systematic review of preclinical studies investigating the treatment of pulmonary fibrosis with hAECs to provide suggestions for their clinical use
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
