Cell Therapy in Idiopathic Pulmonary Fibrosis†

Anna Serrano-Mollar

doi:10.3390/medsci6030064

Cell Therapy in Idiopathic Pulmonary Fibrosis†

Medical Sciences ◽

10.3390/medsci6030064 ◽

2018 ◽

Vol 6 (3) ◽

pp. 64 ◽

Cited By ~ 4

Author(s):

Anna Serrano-Mollar

Keyword(s):

Stem Cells ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Current Knowledge ◽

Treatment Options ◽

Fatal Disease ◽

Cell Therapies ◽

Promising Therapeutic Approach ◽

Preclinical Animal Models ◽

Lung Progenitor

Idiopathic pulmonary fibrosis is a fatal disease with no effective or curative treatment options. In recent decades, cell-based therapies using stem cells or lung progenitor cells to regenerate lung tissue have experienced rapid growth in both preclinical animal models and translational clinical studies. In this review, the current knowledge of these cell therapies is summarized. Although further investigations are required, these studies indicate that cell therapies are a promising therapeutic approach for the treatment of idiopathic pulmonary fibrosis.

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Idiopathic pulmonary fibrosis: lessons from clinical trials over the past 25 years

European Respiratory Journal ◽

10.1183/13993003.01209-2017 ◽

2017 ◽

Vol 50 (4) ◽

pp. 1701209 ◽

Cited By ~ 56

Author(s):

Ganesh Raghu

Keyword(s):

Clinical Trials ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Treatment Options ◽

Phase Iii ◽

Fatal Disease ◽

The Past ◽

Efficacious Treatment ◽

Phase Iii Trials ◽

First Time

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease. A major breakthrough in treatment came when, after decades of clinical trials which failed to identify an efficacious treatment regimen, two therapies were successful in Phase-III trials. The advent of these therapies, nintedanib and pirfenidone, meant that for the first time IPF patients had two treatment options that could reduce disease progression. This review summarises the key lessons to be obtained from the clinical trials that led to the current international clinical practice guidelines for the treatment of IPF and provides insights for the design of future clinical trials that are needed if we are to improve outcomes that are clinically meaningful to IPF patients.

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microRNA-186 in extracellular vesicles from bone marrow mesenchymal stem cells alleviates idiopathic pulmonary fibrosis via interaction with SOX4 and DKK1

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02083-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jing Zhou ◽

Yang Lin ◽

Xiuhua Kang ◽

Zhicheng Liu ◽

Wei Zhang ◽

...

Keyword(s):

Bone Marrow ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Extracellular Vesicles ◽

Luciferase Assay ◽

Therapeutic Effects ◽

Loss Of Function ◽

Fibroblast Activation ◽

Promising Therapeutic Approach

Abstract Background Previous reports have identified that human bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) with their cargo microRNAs (miRNAs) are a promising therapeutic approach for the treatment of idiopathic pulmonary fibrosis (IPF). Therefore, we explored whether delivery of microRNA-186 (miR-186), a downregulated miRNA in IPF, by BMSC EVs could interfere with the progression of IPF in a murine model. Methods In a co-culture system, we assessed whether BMSC-EVs modulated the activation of fibroblasts. We established a mouse model of PF to evaluate the in vivo therapeutic effects of BMSC-EVs and determined miR-186 expression in BMSC-EVs by polymerase chain reaction. Using a loss-of-function approach, we examined how miR-186 delivered by BMSC-EVs affected fibroblasts. The putative relationship between miR-186 and SRY-related HMG box transcription factor 4 (SOX4) was tested using luciferase assay. Next, we investigated whether EV-miR-186 affected fibroblast activation and PF by targeting SOX4 and its downstream gene, Dickkopf-1 (DKK1). Results BMSC-EVs suppressed lung fibroblast activation and delayed IPF progression in mice. miR-186 was downregulated in IPF but enriched in the BMSC-EVs. miR-186 delivered by BMSC-EVs could suppress fibroblast activation. Furthermore, miR-186 reduced the expression of SOX4, a target gene of miR-186, and hence suppressed the expression of DKK1. Finally, EV-delivered miR-186 impaired fibroblast activation and alleviated PF via downregulation of SOX4 and DKK1. Conclusion In conclusion, miR-186 delivered by BMSC-EVs suppressed SOX4 and DKK1 expression, thereby blocking fibroblast activation and ameliorating IPF, thus presenting a novel therapeutic target for IPF.

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Cell therapy for lung disease

European Respiratory Review ◽

10.1183/16000617.0044-2017 ◽

2017 ◽

Vol 26 (144) ◽

pp. 170044 ◽

Cited By ~ 33

Author(s):

Sabine Geiger ◽

Daniela Hirsch ◽

Felix G. Hermann

Keyword(s):

Clinical Studies ◽

Therapeutic Approach ◽

Lung Diseases ◽

Distress Syndrome ◽

Treatment Options ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Cell Therapies ◽

Promising Therapeutic Approach ◽

Preclinical And Clinical Studies

Besides cancer and cardiovascular diseases, lung disorders are a leading cause of morbidity and death worldwide. For many disease conditions no effective and curative treatment options are available. Cell therapies offer a novel therapeutic approach due to their inherent anti-inflammatory and anti-fibrotic properties. Mesenchymal stem/stromal cells (MSC) are the most studied cell product. Numerous preclinical studies demonstrate an improvement of disease-associated parameters after MSC administration in several lung disorders, including chronic obstructive pulmonary disease, acute respiratory distress syndrome and idiopathic pulmonary fibrosis. Furthermore, results from clinical studies using MSCs for the treatment of various lung diseases indicate that MSC treatment in these patients is safe. In this review we summarise the results of preclinical and clinical studies that indicate that MSCs are a promising therapeutic approach for the treatment of lung diseases. Nevertheless, further investigations are required.

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Regulatory Immune Cells in Idiopathic Pulmonary Fibrosis: Friends or Foes?

Frontiers in Immunology ◽

10.3389/fimmu.2021.663203 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chiel van Geffen ◽

Astrid Deißler ◽

Markus Quante ◽

Harald Renz ◽

Dominik Hartl ◽

...

Keyword(s):

Immune System ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Immune Responses ◽

Immune Cells ◽

Current Knowledge ◽

Suppressor Cells ◽

Interstitial Lung Diseases ◽

Stromal Stem Cells

The immune system is receiving increasing attention for interstitial lung diseases, as knowledge on its role in fibrosis development and response to therapies is expanding. Uncontrolled immune responses and unbalanced injury-inflammation-repair processes drive the initiation and progression of idiopathic pulmonary fibrosis. The regulatory immune system plays important roles in controlling pathogenic immune responses, regulating inflammation and modulating the transition of inflammation to fibrosis. This review aims to summarize and critically discuss the current knowledge on the potential role of regulatory immune cells, including mesenchymal stromal/stem cells, regulatory T cells, regulatory B cells, macrophages, dendritic cells and myeloid-derived suppressor cells in idiopathic pulmonary fibrosis. Furthermore, we review the emerging role of regulatory immune cells in anti-fibrotic therapy and lung transplantation. A comprehensive understanding of immune regulation could pave the way towards new therapeutic or preventive approaches in idiopathic pulmonary fibrosis.

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Epithelial–Mesenchymal Transition in the Pathogenesis of Idiopathic Pulmonary Fibrosis

Medicina ◽

10.3390/medicina55040083 ◽

2019 ◽

Vol 55 (4) ◽

pp. 83 ◽

Cited By ~ 23

Author(s):

Francesco Salton ◽

Maria Volpe ◽

Marco Confalonieri

Keyword(s):

Epithelial Cells ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Epithelial Mesenchymal Transition ◽

Treatment Options ◽

Alveolar Epithelium ◽

Alveolar Epithelial Cells ◽

Mesenchymal Transition ◽

Alveolar Epithelial ◽

Serious Disease

Idiopathic pulmonary fibrosis (IPF) is a serious disease of the lung, which leads to extensive parenchymal scarring and death from respiratory failure. The most accepted hypothesis for IPF pathogenesis relies on the inability of the alveolar epithelium to regenerate after injury. Alveolar epithelial cells become apoptotic and rare, fibroblasts/myofibroblasts accumulate and extracellular matrix (ECM) is deposited in response to the aberrant activation of several pathways that are physiologically implicated in alveologenesis and repair but also favor the creation of excessive fibrosis via different mechanisms, including epithelial–mesenchymal transition (EMT). EMT is a pathophysiological process in which epithelial cells lose part of their characteristics and markers, while gaining mesenchymal ones. A role for EMT in the pathogenesis of IPF has been widely hypothesized and indirectly demonstrated; however, precise definition of its mechanisms and relevance has been hindered by the lack of a reliable animal model and needs further studies. The overall available evidence conceptualizes EMT as an alternative cell and tissue normal regeneration, which could open the way to novel diagnostic and prognostic biomarkers, as well as to more effective treatment options.

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Idiopathic pulmonary fibrosis: Current knowledge, future perspectives and its importance in radiation oncology

Radiotherapy and Oncology ◽

10.1016/j.radonc.2020.11.020 ◽

2021 ◽

Vol 155 ◽

pp. 269-277

Author(s):

Görkem Türkkan ◽

Yves Willems ◽

Lizza E.L. Hendriks ◽

Rémy Mostard ◽

Lennart Conemans ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Radiation Oncology ◽

Current Knowledge ◽

Future Perspectives

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Idiopathic Pulmonary Fibrosis and Lung Cancer: Mechanisms and Molecular Targets

International Journal of Molecular Sciences ◽

10.3390/ijms20030593 ◽

2019 ◽

Vol 20 (3) ◽

pp. 593 ◽

Cited By ~ 35

Author(s):

Beatriz Ballester ◽

Javier Milara ◽

Julio Cortijo

Keyword(s):

Lung Cancer ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Current Knowledge ◽

Molecular Targets ◽

Small Cell ◽

Small Cell Lung ◽

Mesenchymal Transition ◽

Cellular Processes ◽

History Of

Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pulmonary disease with a median survival of 2–4 years after diagnosis. A significant number of IPF patients have risk factors, such as a history of smoking or concomitant emphysema, both of which can predispose the patient to lung cancer (LC) (mostly non-small cell lung cancer (NSCLC)). In fact, IPF itself increases the risk of LC development by 7% to 20%. In this regard, there are multiple common genetic, molecular, and cellular processes that connect lung fibrosis with LC, such as myofibroblast/mesenchymal transition, myofibroblast activation and uncontrolled proliferation, endoplasmic reticulum stress, alterations of growth factors expression, oxidative stress, and large genetic and epigenetic variations that can predispose the patient to develop IPF and LC. The current approved IPF therapies, pirfenidone and nintedanib, are also active in LC. In fact, nintedanib is approved as a second line treatment in NSCLC, and pirfenidone has shown anti-neoplastic effects in preclinical studies. In this review, we focus on the current knowledge on the mechanisms implicated in the development of LC in patients with IPF as well as in current IPF and LC-IPF candidate therapies based on novel molecular advances.

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