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

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Abstract

Pulmonary fibrosis (PF) is a progressive and irreversible lung disease, characterized by poor prognosis with limited treatment options. Mesenchymal stem cells (MSCs) are multi-potent cells having the ability to self-renew and differentiate into multiple tissues, thus considered a novel treatment option. The present study aimed to investigate the possible antifibrotic effect of undifferentiated adipose tissue–derived mesenchymal stem cell (AD-MSC) therapy on PF experimentally induced in rats using amiodarone (AMD). AMD (30 mg/kg) was given orally, once daily for 12 consecutive weeks to induce lung fibrosis. Following the confirmation of lung damage with histopathological examination, AD-MSCs (2 × 106 and 4 × 106 undifferentiated MSCs) were injected once intravenously, followed by 2 months for treatment. AMD induced focal fibroblastic cells proliferation in the peribronchiolar tissue, as well as in between the collapsed emphysematous alveoli. Also, AMD significantly increased serum and lung homogenate fibroblast growth factor-7 (FGF7), Clara cell protein-16 (CC16), and cytokeratin -19 (CK19) levels, as well as the expression of both iNOS and NFкB in the lung alveoli. Moreover, AMD caused excessive collagen deposition and increased alpha smooth muscle actin (α-SMA) expression. All findings significantly regressed on stem cell therapy in both doses, with superior effect of the high dose, providing evidence that adipose tissue–derived MSCs could be a promising approach for the treatment of PF.

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Authors and Affiliations

  1. Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt

    Sara M. Radwan

  2. Faculty of Pharmacy, Ain Shams University, Cairo, Egypt

    Dalia Ghoneim, Manar Salem, Menna Saeed, Yara Saleh, Mohanad Elhamy, Kholoud Wael & Omnia Shokair

  3. Pharmacology and Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt

    Sara A. Wahdan

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  1. Sara M. Radwan
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All authors whose names appear on the submission (1) made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data; or the creation of new software used in the work; (2) drafted the work or revised it critically for important intellectual content; (3) approved the version to be published; and (4) agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Sara A. Wahdan.

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Radwan, S.M., Ghoneim, D., Salem, M. et al. Adipose Tissue–Derived Mesenchymal Stem Cells Protect Against Amiodarone-Induced Lung Injury in Rats. Appl Biochem Biotechnol 191, 1027–1041 (2020). https://doi.org/10.1007/s12010-020-03227-8

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