ArticleStem cells (Dayton, Ohio)2018
Alpha-Klotho Enrichment in Induced Pluripotent Stem Cell Secretome Contributes to Antioxidative Protection in Acute Lung Injury.
Article in Stem cells (Dayton, Ohio), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Activation of Nrf2 with natural flavonoids and mesenchymal stromal/stem cells: mechanisms and therapeutic potential for inflammatory diseases.Stem cell research & therapy · 2026Review
- The Application and Challenges of Stem Cell-Derived Extracellular Vesicles in Inhalation Lung Injury.International journal of nanomedicine · 2026Review
- Advances in research on hyperoxia-induced acute lung injury: from pathogenesis to therapy.Frontiers in cell and developmental biology · 2026Review
- Nebulization of Mesenchymal Stem Cells Secretome Attenuates Acute Respiratory Distress Syndrome Caused by SARS-CoV-2 Corona Virus: An Open-Label, Controlled Trial.Advanced biomedical research · 2025Article
- Extracellular vesicle-mediated cellular crosstalk in lung repair, remodelling and regeneration.European respiratory review : an official journal of the European Respiratory Society · 2022Review
- The Neglected Price of Pediatric Acute Kidney Injury: Non-renal Implications.Frontiers in pediatrics · 2022Review
- Constitutive transgenic α-Klotho overexpression enhances resilience to and recovery from murine acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Interactome Analysis of iPSC Secretome and Its Effect on Macrophages In Vitro.International journal of molecular sciences · 2021Article
- Bovine serum albumin aggravates macrophage M1 activation and kidney injury in heterozygous Klotho-deficient mice via the gut microbiota-immune axis.International journal of biological sciences · 2021Article
- Two to Tango: Kidney-Lung Interaction in Acute Kidney Injury and Acute Respiratory Distress Syndrome.Frontiers in pediatrics · 2021Review
- Inhalational delivery of induced pluripotent stem cell secretome improves postpneumonectomy lung structure and function.Journal of applied physiology (Bethesda, Md. : 1985) · 2020Article
- Intranasal Administration of Mesenchymal Stem Cell Secretome Reduces Hippocampal Oxidative Stress, Neuroinflammation and Cell Death, Improving the Behavioral Outcome Following Perinatal Asphyxia.International journal of molecular sciences · 2020Article
- Article
- Klotho Alleviates Lung Injury Caused by Paraquat via Suppressing ROS/P38 MAPK-Regulated Inflammatory Responses and Apoptosis.Oxidative medicine and cellular longevity · 2020Article
- Human induced pluripotent stem cells ameliorate hyperoxia-induced lung injury in a mouse model.American journal of translational research · 2020Article
- Alpha-Klotho, a critical protein for lung health, is not expressed in normal lung.FASEB bioAdvances · 2019Article
- Subtle Difference Generates Big Dissimilarity: Comparison of Enzymatic Activity in KL1 and KL2 Domains of Lancelet Klotho.Marine biotechnology (New York, N.Y.) · 2019Article
- The Effects of the Anti-aging Protein Klotho on Mucociliary Clearance.Frontiers in medicine · 2019Article
- Proteomic analysis of human mesenchymal stromal cell secretomes: a systematic comparison of the angiogenic potential.NPJ Regenerative medicine · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Induced pluripotent stem cells (iPSCs) have been reported to alleviate organ injury, although the mechanisms of action remain unclear and administration of intact cells faces many limitations. We hypothesized that cell-free conditioned media (CM) containing the secretome of iPSCs possess antioxidative constituents that can alleviate pulmonary oxidant stress damage. We derived iPSCs from human dermal fibroblasts and harvested the CM. Addition of iPSC CM to cultured human alveolar type-1 epithelial cells mitigated hyperoxia-induced depletion of endogenous total antioxidant capacity while tracheal instillation of iPSC CM into adult rat lungs enhanced hyperoxia-induced increase in TAC. In both the in vitro and in vivo models, iPSC CM ameliorated oxidative damage to DNA, lipid, and protein, and activated the nuclear factor (erythroid 2)-related factor 2 (Nrf2) network of endogenous antioxidant proteins. Compared with control fibroblast-conditioned or cell-free media, iPSC CM is highly enriched with αKlotho at a concentration up to more than 10-fold of that in normal serum. αKlotho is an essential antioxidative cell maintenance and protective factor and an activator of the Nrf2 network. Immunodepletion of αKlotho reduced iPSC CM-mediated cytoprotection by ∼50%. Thus, the abundant αKlotho content significantly contributes to iPSC-mediated antioxidation and cytoprotection. Results uncover a major mechanism of iPSC action, suggest a fundamental role of αKlotho in iPSC maintenance, and support the translational potential of airway delivery of cell-free iPSC secretome for protection against lung injury. The targeted cell-free secretome-based approach may also be applicable to the amelioration of injury in other organs. Stem Cells 2018;36:616-625.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.