Decidualization modulates the mesenchymal stromal/stem cell and pericyte characteristics of human decidual stromal cells. Effects on antigen expression, chemotactic activity on monocytes and antitumoral activity

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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Adipose-derived mesenchymal stromal/stem cells in systemic sclerosis: Alterations in function and beneficial effect on lung fibrosis are regulated by caveolin-1

Journal of Scleroderma and Related Disorders ◽

10.1177/2397198318821510 ◽

2019 ◽

Vol 4 (2) ◽

pp. 127-136 ◽

Cited By ~ 4

Author(s):

Rebecca Lee ◽

Nicoletta Del Papa ◽

Martin Introna ◽

Charles F Reese ◽

Marina Zemskova ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Systemic Sclerosis ◽

Transforming Growth Factor ◽

Stem Cell Differentiation ◽

Caveolin 1 ◽

Stromal Stem Cell ◽

Mesenchymal Stromal Stem Cell ◽

Domain Peptide ◽

Stromal Stem Cells

The potential value of mesenchymal stromal/stem cell therapy in treating skin fibrosis in scleroderma (systemic sclerosis) and of the caveolin-1 scaffolding domain peptide in treating lung, skin, and heart fibrosis is known. To understand how these observations may relate to differences between mesenchymal stromal/stem cells from healthy subjects and subjects with fibrosis, we have characterized the fibrogenic and adipogenic potential of adipose-derived mesenchymal stromal/stem cells from systemic sclerosis patients, from mice with fibrotic lung and skin disease induced by systemic bleomycin treatment, and from healthy controls. Early passage systemic sclerosis adipose-derived mesenchymal stromal/stem cells have a profibrotic/anti-adipogenic phenotype compared to healthy adipose-derived mesenchymal stromal/stem cells (low caveolin-1, high α-smooth muscle actin, high HSP47, low pAKT, low capacity for adipogenic differentiation). This phenotype is mimicked by treating healthy adipose-derived mesenchymal stromal/stem cells with transforming growth factor beta or caveolin-1 small interfering RNA and is reversed in systemic sclerosis adipose-derived mesenchymal stromal/stem cells by treatment with caveolin-1 scaffolding domain peptide, but not scrambled caveolin-1 scaffolding domain peptide. Similar results were obtained with adipose-derived mesenchymal stromal/stem cells from systemic sclerosis patients and from bleomycin-treated mice, indicating the central role of caveolin-1 in mesenchymal stromal/stem cell differentiation in fibrotic disease.

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