Adipose Tissue–Derived Mesenchymal Stem Cells Protect Against Amiodarone-Induced Lung Injury in Rats

Radwan, Sara M.; Ghoneim, Dalia; Salem, Maha M.; Saeed, Menna; Saleh, Yara; Elhamy, Mohanad; Wael, Kholoud; Shokair, Omnia; Wahdan, Sara A.

doi:10.1007/s12010-020-03227-8

Cited by 15 publications

(11 citation statements)

References 44 publications

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“…A variety of studies showed attenuated, but not resolved, fibrosis after ASC treatment in bleomycin-induced lung fibrosis in mice and rats ( Lee et al, 2014 ; Jiang et al, 2015 ; Tashiro et al, 2015 ; Rathinasabapathy et al, 2016 ; Reddy et al, 2016 ; Llontop et al, 2018 ; Felix et al, 2020 ). Similar results were achieved in other rat models of pulmonary fibrosis ( Fikry et al, 2015 ; Chen et al, 2018 ; Zhang et al, 2019 ; Radwan et al, 2020 ). A phase Ib, non-randomized clinical trial in patients with IPF has shown that even though administration of ASCs was safe and hinted toward advantageous short-term effects, the long-term follow-up showed unaltered disease progression and survival rates ( Tzouvelekis et al, 2013 ; Ntolios et al, 2018 ).…”

Section: Introductionsupporting

confidence: 88%

Adipose Stromal Cell-Secretome Counteracts Profibrotic Signals From IPF Lung Matrices

Vasse

Jager

et al. 2021

Front. Pharmacol.

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Introduction: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by excess deposition and altered structure of extracellular matrix (ECM) in the lungs. The fibrotic ECM is paramount in directing resident cells toward a profibrotic phenotype. Collagens, an important part of the fibrotic ECM, have been shown to be structurally different in IPF. To further understand the disease to develop better treatments, the signals from the ECM that drive fibrosis need to be identified. Adipose tissue-derived stromal cell conditioned medium (ASC-CM) has demonstrated antifibrotic effects in animal studies but has not been tested in human samples yet. In this study, the collagen structural integrity in (fibrotic) lung tissue, its interactions with fibroblasts and effects of ASC-CM treatment hereon were studied.Methods: Native and decellularized lung tissue from patients with IPF and controls were stained for denatured collagen using a collagen hybridizing peptide. Primary lung fibroblasts were seeded into decellularized matrices from IPF and control subjects and cultured for 7 days in the presence or absence of ASC-CM. Reseeded matrices were fixed, stained and analyzed for total tissue deposition and specific protein expression.Results: In both native and decellularized lung tissue, more denatured collagen was observed in IPF tissue compared to control tissue. Upon recellularization with fibroblasts, the presence of denatured collagen was equalized in IPF and control matrices, whereas total ECM was higher in IPF matrices than in the control. Treatment with ASC-CM resulted in less ECM deposition, but did not alter the levels of denatured collagen.Discussion: Our data showed that ASC-CM can inhibit fibrotic ECM-induced profibrotic behavior of fibroblasts. This process was independent of collagen structural integrity. Our findings open up new avenues for ASC-CM to be explored as treatment for IPF.

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Section: Introductionsupporting

confidence: 88%

Adipose Stromal Cell-Secretome Counteracts Profibrotic Signals From IPF Lung Matrices

Vasse

Jager

et al. 2021

Front. Pharmacol.

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“…It has been demonstrated that MSCs reduce bacterial load and reduce inflammatory markers in pneumonia models [155,156]. Several studies have demonstrated the capacity of MSCs to reduce the inflammatory response characteristic of asthma patients [157] and their regenerative properties in fibrotic diseases such as COPD [158,159]. Several clinical trials are underway in order to prove the safety and efficacy of these treatments [160][161][162][163].…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Future Trends in Nebulized Therapies for Pulmonary Disease

McCarthy

González

Higgins

2020

JPM

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Aerosol therapy is a key modality for drug delivery to the lungs of respiratory disease patients. Aerosol therapy improves therapeutic effects by directly targeting diseased lung regions for rapid onset of action, requiring smaller doses than oral or intravenous delivery and minimizing systemic side effects. In order to optimize treatment of critically ill patients, the efficacy of aerosol therapy depends on lung morphology, breathing patterns, aerosol droplet characteristics, disease, mechanical ventilation, pharmacokinetics, and the pharmacodynamics of cell-drug interactions. While aerosol characteristics are influenced by drug formulations and device mechanisms, most other factors are reliant on individual patient variables. This has led to increased efforts towards more personalized therapeutic approaches to optimize pulmonary drug delivery and improve selection of effective drug types for individual patients. Vibrating mesh nebulizers (VMN) are the dominant device in clinical trials involving mechanical ventilation and emerging drugs. In this review, we consider the use of VMN during mechanical ventilation in intensive care units. We aim to link VMN fundamentals to applications in mechanically ventilated patients and look to the future use of VMN in emerging personalized therapeutic drugs.

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“…Collagen deposition was assayed as a marker of fibrosis. [ 17 ] Masson's trichrome staining images showed that normal rats had fine collagen fibers distributed in the peribronchiolar area and the interalveolar septa, whereas oral rats showed dense collagen fiber deposition in the interalveolar septa, and around pulmonary bronchioles and blood vessels. This result was confirmed by collagen content analysis based on Masson's trichrome staining (Figure 3b).…”

Section: Resultsmentioning

confidence: 99%

Reservoir Microneedle Patch Mitigates Postsurgical Atrial Fibrillation

Wang,

Chen,

Huang

et al. 2024

Adv Funct Materials

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Oral amiodarone for 3–6 months is commonly required for the prevention and treatment of atrial fibrillation (AF) after surgical ablation of refractory AF. However, clinical data show that oral administration is likely to cause systemic toxicity, especially pulmonary fibrosis. Here, a new strategy is described for the treatment and prevention of postsurgical AF via the epicardial application of a monolithic reservoir microneedle device. These findings demonstrate that this strategy enables a sustained transport of amiodarone directly to the atrium, thereby maximizing therapeutic efficacy and minimizing systemic drug distribution. Notably, a significantly reduced drug dosage (only one dose of 6.3 mg for reservoir MNs versus a daily dose of ≈10 mg for oral administration) achieves therapeutic efficacy over a long period of 24 weeks in a rat AF model, circumventing the risks of pulmonary fibrosis associated with oral administration. This device can serve as a promising alternative to oral amiodarone, providing a robust therapeutic strategy for the prevention and treatment of postsurgical AF is antipicated.

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Adipose Tissue–Derived Mesenchymal Stem Cells Protect Against Amiodarone-Induced Lung Injury in Rats

Cited by 15 publications

References 44 publications

Adipose Stromal Cell-Secretome Counteracts Profibrotic Signals From IPF Lung Matrices

Adipose Stromal Cell-Secretome Counteracts Profibrotic Signals From IPF Lung Matrices

Future Trends in Nebulized Therapies for Pulmonary Disease

Reservoir Microneedle Patch Mitigates Postsurgical Atrial Fibrillation

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