The Use of Mesenchymal Stromal Cells in Treatment of Lung Disorders

Kardia, Egi; Zakaria, Norashikin; Halim, Nur Shuhaidatul Sarmiza Abdul; Widera, Darius; Yahaya, Badrul Hisham

doi:10.2217/rme-2016-0112

Cited by 8 publications

(3 citation statements)

References 130 publications

(139 reference statements)

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“… 114 Many studies support the ability of these cells to convert into airway and epithelial cells 115 and to promote lung repair and regeneration through MSC paracrine release, which is also influenced by extracellular vesicles (EVs). 116 , 117 However, many issues need to be considered before treating patients with MSCs. Often the pathogeneses of lung disorders are not completely known, and the molecular target to trigger and the MSC biodistribution in the damaged tissue need to be considered.…”

Section: Main Textmentioning

confidence: 99%

Dissecting the Pharmacodynamics and Pharmacokinetics of MSCs to Overcome Limitations in Their Clinical Translation

Salvadori

Cesari

Murgia

et al. 2019

Molecular Therapy - Methods & Clinical Development

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Recently, mesenchymal stromal stem cells (MSCs) have been proposed as therapeutic agents because of their promising preclinical features and good safety profile. However, their introduction into clinical practice has been associated with a suboptimal therapeutic profile. In this review, we address the biodistribution of MSCs in preclinical studies with a focus on the current understanding of the pharmacodynamics (PD) and pharmacokinetics (PK) of MSCs as key aspects to overcome unsatisfactory clinical benefits of MSC application. Beginning with evidence of MSC biodistribution and highlighting PK and PD factors, a new PK-PD model is also proposed. According to this theory, MSCs and their released factors are key players in PK, and the efficacy biomarkers are considered relevant for PD in more predictive preclinical investigations. Accounting for the PK-PD relationship in MSC translational research and proposing new models combined with better biodistribution studies could allow realization of the promise of more robust MSC clinical translation.

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Section: Main Textmentioning

confidence: 99%

Dissecting the Pharmacodynamics and Pharmacokinetics of MSCs to Overcome Limitations in Their Clinical Translation

Salvadori

Cesari

Murgia

et al. 2019

Molecular Therapy - Methods & Clinical Development

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“…Recently, mesenchymal stem cells (MSCs) have emerged as a compelling cellular therapy due to their remarkable regenerative capabilities. As a versatile treatment approach, MSCs hold great potential in facilitating the repair and regeneration of damaged lung tissue [9][10][11]. Many experimental studies have proved that the paracrine function of MSCs plays an indispensable role in the process of tissue repair [12].…”

Section: Introductionmentioning

confidence: 99%

MiR-148a-3p within HucMSC-Derived Extracellular Vesicles Suppresses Hsp90b1 to Prevent Fibroblast Collagen Synthesis and Secretion in Silica-Induced Pulmonary Fibrosis

Jiang,

Zhao,

Jia

et al. 2023

IJMS

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Silicosis is a fatal occupational respiratory disease caused by the prolonged inhalation of respirable silica. The core event of silicosis is the heightened activity of fibroblasts, which excessively synthesize extracellular matrix (ECM) proteins. Our previous studies have highlighted that human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs) hold promise in mitigating silicosis and the significant role played by microRNAs (miRNAs) in this process. Delving deeper into this mechanism, we found that miR-148a-3p was the most abundant miRNA of the differential miRNAs in hucMSC-EVs, with the gene heat shock protein 90 beta family member 1 (Hsp90b1) as a potential target. Notably, miR-148a-3p’s expression was downregulated during the progression of silica-induced pulmonary fibrosis both in vitro and in vivo, but was restored after hucMSC-EVs treatment (p < 0.05). Introducing miR-148a-3p mimics effectively hindered the collagen synthesis and secretion of fibroblasts induced by transforming growth factor-β1 (TGF-β1) (p < 0.05). Confirming our hypothesis, Hsp90b1 was indeed targeted by miR-148a-3p, with significantly reduced collagen activity in TGF-β1-treated fibroblasts upon Hsp90b1 inhibition (p < 0.05). Collectively, our findings provide compelling evidence that links miR-148a-3p present in hucMSC-EVs with the amelioration of silicosis, suggesting its therapeutic potential by specifically targeting Hsp90b1, thereby inhibiting fibroblast collagen activities. This study sheds light on the role of miR-148a-3p in hucMSC-EVs, opening avenues for innovative therapeutic interventions targeting molecular pathways in pulmonary fibrosis.

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“…Overall, plenty of preclinical studies have provided congruent and convincing evidence of MSC therapy effectiveness in treating many lung disorders. As recently reviewed, treatment with MSCs improved disease-associated parameters in acute respiratory distress syndrome (ARDS) [11] as well as bronchopulmonary dysplasia, chronic obstructive pulmonary disease, pulmonary hypertension and idiopathic pulmonary fibrosis [12][13][14][15]. To date, only two papers have considered MSCs for the treatment of COVID-19 pneumonia.…”

mentioning

confidence: 99%

Mesenchymal Stromal Cell Secretome for Severe COVID-19 Infections: Premises for the Therapeutic Use

Bari

Ferrarotti

Saracino

et al. 2020

Cells

114

126

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From the end of 2019, the world population has been faced the spread of the novel coronavirus SARS-CoV-2 responsible for COVID-19 infection. In approximately 14% of the patients affected by the novel coronavirus, the infection progresses with the development of pneumonia that requires mechanical ventilation. At the moment, there is no specific antiviral treatment recommended for the COVID-19 pandemic and the therapeutic strategies to deal with the infection are only supportive. In our opinion, mesenchymal stem cell secretome could offer a new therapeutic approach in treating COVID-19 pneumonia, due to the broad pharmacological effects it shows, including anti-inflammatory, immunomodulatory, regenerative, pro-angiogenic and anti-fibrotic properties.

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The Use of Mesenchymal Stromal Cells in Treatment of Lung Disorders

Cited by 8 publications

References 130 publications

Dissecting the Pharmacodynamics and Pharmacokinetics of MSCs to Overcome Limitations in Their Clinical Translation

Dissecting the Pharmacodynamics and Pharmacokinetics of MSCs to Overcome Limitations in Their Clinical Translation

MiR-148a-3p within HucMSC-Derived Extracellular Vesicles Suppresses Hsp90b1 to Prevent Fibroblast Collagen Synthesis and Secretion in Silica-Induced Pulmonary Fibrosis

Mesenchymal Stromal Cell Secretome for Severe COVID-19 Infections: Premises for the Therapeutic Use

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