Safety and Tolerability of Alveolar Type II Cell Transplantation in Idiopathic Pulmonary Fibrosis

Serrano-Mollar, Anna; Gay-Jordi, Gemma; Guillamat-Prats, Raquel; Closa, Daniel; Hernández-González, Fernanda; Marı́n, Pedro; Burgos, Felip; Martorell, Jaume; Sánchez, Marcelo; Arguis, Pedro; Soy, Dolors; Bayas, José M.; Ramírez, Josep; Tetley, Teresa D.; Molins, Laureano; Bellacasa, Jordi Puig de la; Rodríguez‐Villar, C.; Rovira, I.; Fibla, Juan J.; Xaubet, Antoni

doi:10.1016/j.chest.2016.03.021

Cited by 58 publications

(48 citation statements)

References 24 publications

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“…In the small number of IPF patients whom have been reported on, there have been no serious adverse events identified. One patient in the Serrano-Mollar study developed a transitory alveolar infiltrate and hypoxemia after cell instillation that responded rapidly to steroids [12]. Chambers and colleagues reported only mild adverse events, including a transient decrease in arterial oxygen saturation [13].…”

Section: Discussionmentioning

confidence: 99%

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Acute Respiratory Failure in a Patient With Idiopathic Pulmonary Fibrosis Following Nebulized and Intravenous Stem Cell Therapy

et al. 2017

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Idiopathic pulmonary fibrosis (IPF) is an uncommon disease with a poor prognosis. Recently, two medications were approved to slow progression of disease. However, due to the limited treatment options available, patients and their families often look to experimental and off-label treatments for support. One such option is stem cell therapy, which can be delivered in a variety of ways. Stem cells are being utilized both in and out of the context of closely monitored clinical trials. However, there is little evidence regarding the safety and efficacy of stem cell therapy for patients with IPF. Here we describe a case of a patient who received intravenous and nebulized stem cell therapy, which was followed by an acute exacerbation of his IPF. The exacerbation was successfully treated with corticosteroids and supportive care.

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Section: Discussionmentioning

confidence: 99%

“…Sources have included bone marrow [8][9][10], adipose tissue [11], lung (from both live and deceased donors) [12], and placentas [13]. Once cultivated, several ways of reintroducing stem cells have been described, including by IV infusion [8,10,14], nebulization and bronchoscopy [11,12].…”

Section: Discussionmentioning

confidence: 99%

Acute Respiratory Failure in a Patient With Idiopathic Pulmonary Fibrosis Following Nebulized and Intravenous Stem Cell Therapy

et al. 2017

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“…In recent years, at least three phase 1b non-randomized non-placebo clinical trials involving stem cells and a clinical study using the lung stem/progenitor ATII cells have been published [ 35 , 36 , 37 , 38 ]. The main objective of these studies was to evaluate the safety and tolerability of the administered cells.…”

Section: Clinical Experiencesmentioning

confidence: 99%

“…In the other clinical study, ATII cells isolated from lungs of organ donors were administered endotracheally, at a dose of 1000 to 1200 × 10 6 cells/patient, into 16 patients diagnosed with mild to moderate and progressive disease [ 37 ]. In this study, to avoid ATII cell rejection reactions, patients followed immunosuppressive and prophylaxis treatment and the rate of sensitization due to ATII cell administration was similar to that observed in a blood transfusion [ 37 ]. No relevant side effects were observed, and 13 of the 16 patients showed stabilization in the functional tests performed throughout the one-year follow-up.…”

Section: Clinical Experiencesmentioning

confidence: 99%

Cell Therapy in Idiopathic Pulmonary Fibrosis†

Serrano-Mollar

2018

Medical Sciences

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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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“…Most PF patients show a progressive decline in pulmonary function, which eventually leads to respiratory failure and death. 1 Conventional therapy consisting of glucocorticoids or immunosuppressive drugs has been affirmed ineffective. Currently, lung transplantation is considered to be an effective treatment approach, but only in limited number of patients, with a 5 year post-transplantation survival rate of about 50%.…”

Section: Introductionmentioning

confidence: 99%

Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice

Peng

Zhang

et al. 2017

Genes & Diseases

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Alveolar epithelial cells (AECs) injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis (PF). Nevertheless, the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear. SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is essential for kidney and heart fibrosis. We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II (ATII) cells. Moreover, we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO)7-Cre/SMARCA4f/f mice (SOSM4Δ/Δ) model, as well as a new SMARCA4-deleted alveolar type II (ATII)-like mle-12 cell line. We found that the bleomycin-induced PF was more aggressive in SOSM4Δ/Δ mice. Also, the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro. In addition, we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections. These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells, which might affect the progression of PF.

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Safety and Tolerability of Alveolar Type II Cell Transplantation in Idiopathic Pulmonary Fibrosis

Cited by 58 publications

References 24 publications

Acute Respiratory Failure in a Patient With Idiopathic Pulmonary Fibrosis Following Nebulized and Intravenous Stem Cell Therapy

Acute Respiratory Failure in a Patient With Idiopathic Pulmonary Fibrosis Following Nebulized and Intravenous Stem Cell Therapy

Cell Therapy in Idiopathic Pulmonary Fibrosis†

Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice

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