English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Background  During myocardial ischemia/reperfusion ( MI /R) injury, there is extensive release of immunogenic metabolites that activate cells of the innate immune system. These include  ATP  and  AMP , which upregulate chemotaxis, migration, and effector function of early infiltrating inflammatory cells. These cells subsequently drive further tissue devitalization. Mesenchymal stromal cells ( MSC s) are a potential treatment modality for  MI /R because of their powerful anti‐inflammatory capabilities; however, the manner in which they regulate the acute inflammatory milieu requires further elucidation.  CD 73, an ecto‐5′‐nucleotidase, may be critical in regulating inflammation by converting pro‐inflammatory  AMP  to anti‐inflammatory adenosine. We hypothesized that  MSC ‐mediated conversion of  AMP  into adenosine reduces inflammation in early  MI /R, favoring a micro‐environment that attenuates excessive innate immune cell activation and facilitates earlier cardiac recovery.    Methods and Results  Adult rats were subjected to 30 minutes of  MI /R injury.  MSC s were encapsulated within a hydrogel vehicle and implanted onto the myocardium. A subset of  MSC s were pretreated with the  CD 73 inhibitor, α,β‐methylene adenosine diphosphate, before implantation. Using liquid chromatography/mass spectrometry, we found that  MSC s increase myocardial adenosine availability following injury via  CD 73 activity.  MSC s also reduce innate immune cell infiltration as measured by flow cytometry, and hydrogen peroxide formation as measured by Amplex Red assay. These effects were dependent on  MSC ‐mediated  CD 73 activity. Finally, through echocardiography we found that  CD 73 activity on  MSC s was critical to optimal protection of cardiac function following  MI /R injury.    Conclusions   MSC ‐mediated conversion of  AMP  to adenosine by  CD 73 exerts a powerful anti‐inflammatory effect critical for cardiac recovery following  MI /R injury.

journal of the american heart association

Adenosine Production by Biomaterial‐Supported Mesenchymal Stromal Cells Reduces the Innate Inflammatory Response in Myocardial Ischemia/Reperfusion Injury