Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities

Although mesenchymal stromal (stem) cell (MSC) administration attenuates sepsis-induced lung injury in pre-clinical models, the mechanism(s) of action and host immune system contributions to its therapeutic effects, remain elusive. We show that treatment with MSCs decreased expression of host-derived microRNA (miR)-193b-5p and increased expression of its target gene, the tight junctional protein occludin (Ocln), in lungs from septic mice. Mutating the Ocln 3′ UTR miR-193b-5p binding sequence impaired binding to Ocln mRNA. Inhibition of miR-193b-5p in human primary pulmonary microvascular endothelial cells (HPMECs) prevents tumor necrosis factor (TNF)-induced decrease in Ocln gene and protein expression and loss of barrier function. MSC conditioned media mitigated TNF-induced miR-193b-5p upregulation and Ocln downregulation in vitro. When administered in vivo, MSC conditioned media recapitulated the effects of MSC administration on pulmonary miR-193b-5p and Ocln expression. MiR-193b deficient mice were resistant to pulmonary inflammation and injury induced by LPS instillation. Silencing of Ocln in miR-193b deficient mice partially recovered the susceptibility to LPS-induced lung injury. In vivo inhibition of miR-193b-5p protected mice from endotoxin-induced lung injury. Finally, the clinical significance of these results was supported by the finding of increased miR-193b-5p expression levels in lung autopsy samples from Acute Respiratory Distress Syndrome patients who died with diffuse alveolar damage.

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Mesenchymal stromal stem cell therapy in advanced interstitial lung disease - Anaphylaxis and short-term follow-up

Lung India ◽

10.4103/0970-2113.164156 ◽

2015 ◽

Vol 32 (5) ◽

pp. 486 ◽

Cited By ~ 2

Author(s):

Balamugesh Thangakunam ◽

DevasahayamJesudas Christopher ◽

Vikram Mathews ◽

Alok Srivastava

Keyword(s):

Stem Cell ◽

Interstitial Lung Disease ◽

Cell Therapy ◽

Lung Disease ◽

Stem Cell Therapy ◽

Short Term ◽

Stromal Stem Cell ◽

Mesenchymal Stromal Stem Cell

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Mesenchymal stem cell-derived extracellular vesicles in the failing heart: past, present, and future

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00951.2020 ◽

2021 ◽

Author(s):

Catherine Karbasiafshar ◽

Frank W. Sellke ◽

M. Ruhul Abid

Keyword(s):

Stem Cell ◽

Extracellular Vesicles ◽

Treatment Options ◽

Current Treatment ◽

Lifestyle Changes ◽

Challenges And Opportunities ◽

Artery Disease ◽

New Treatment

Cardiovascular disease (CVD) is the leading cause of death globally. Current treatment options include lifestyle changes, medication, and surgical intervention. However, many patients are unsuitable candidates for surgeries due to comorbidities, diffuse coronary artery disease or advanced stages of heart failure. The search for new treatment options has recently transitioned from cell-based therapies to stem-cell derived extracellular vesicles (EVs). A number of challenges remain in the EV field, including the effect of comorbidities, characterization, and delivery, However, recent revolutionary developments and insight into the potential of 'personalizing' EV contents by bioengineering methods to alter specific signaling pathways in the ischemic myocardium hold promise. Here, we discuss the past limitations of cell-based therapies, and recent EV studies involving in vivo, in vitro, and omics, and future challenges and opportunities in EV-based treatments in CVD.

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