Diabetic state of human coronary artery endothelial cells results in altered effects of bone mesenchymal stem cell-derived extracellular vesicles.

Publication/Presentation Date

12-1-2023

Abstract

Human bone mesenchymal stem cell-derived extracellular vesicles (HBMSC-EV) have been used successfully in animal models of myocardial ischemia, yet have dampened effects in metabolic syndrome through unknown mechanisms. This study demonstrates the basal differences between non-diabetic human coronary artery endothelial cells (HCAEC) and diabetic HCAEC (DM-HCAEC), and how these cells respond to the treatment of HBMSC-EV. HCAEC and DM-HCAEC were treated with HBMSC-EV for 6 h. Proteomics, western blot analysis, and tube formation assays were performed. Key metabolic, growth, and stress/starvation cellular responses were significantly altered in DM-HCAEC in comparison to that of HCAEC at baseline. Proteomics demonstrated increased phosphorus metabolic process and immune pathways and decreased RNA processing and biosynthetic pathways in DM-HCAEC. Similar to previous in vivo findings, HCAEC responded to the HBMSC-EV with regenerative and anti-inflammatory effects through the upregulation of multiple RNA pathways and downregulation of immune cell activation pathways. In contrast, DM-HCAEC had a significantly diminished response to HBMSC-EV, likely due to the baseline abnormalities in DM-HCAEC. To achieve the full benefits of HBMSC-EV and for a successful transition of this potential therapeutic agent to clinical studies, the abnormalities found in DM-HCAEC will need to be further studied.

Volume

11

Issue

24

First Page

15866

Last Page

15866

ISSN

2051-817X

Disciplines

Medicine and Health Sciences

PubMedID

38114067

Department(s)

Department of Surgery, Fellows and Residents, Department of Surgery Residents

Document Type

Article

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