# MSCs ameliorates hyperglycemia-induced endothelial injury through modulation of mitochondrial dynamics

## TL;DR

This study shows that mesenchymal stromal cells protect against diabetes-related blood vessel damage by regulating mitochondria through a protein called STC1.

## Contribution

The study identifies STC1 as a novel paracrine factor from MSCs that prevents hyperglycemia-induced endothelial injury via mitochondrial dynamics modulation.

## Key findings

- MSCs reduce hyperglycemia-induced endothelial injury by preventing abnormal mitochondrial fission.
- STC1 secreted by MSCs inhibits ERK1/2 activation and Drp1-mediated mitochondrial damage.
- STC1 protects against oxidative stress, inflammation, and apoptosis in diabetic endothelial dysfunction.

## Abstract

Endothelial dysfunction contributes to the development of cardiovascular disease in patients with diabetes mellitus, and current strategies remain inadequate. Although mesenchymal stromal cells (MSCs) have shown beneficial effects in experimental models of diabetes, underlying mechanisms remain elusive. Here, using a human umbilical vein endothelial cells (HUVECs) treated with high concentration of glucose (HG) and a mouse model of type 2 diabetes (db/db mice), we demonstrate MSCs could alleviate hyperglycemia-induced endothelial injury by preventing aberrant mitochondrial morphology. Mechanistically, stanniocalcin-1(STC1) was identified to be an important paracrine factor secreted by MSCs, which restrains hyperactivation of ERK1/2, thus preventing Drp1-mediated excessive mitochondrial fission, and thereby protecting against hyperglycemia-induced oxidative injury, endothelial inflammation and mitochondrial apoptotic pathway, consequently protecting endothelial dysfunction. Hence, this study reveals that MSCs-derived STC1 regulates mitochondrial dynamics remodeling through inhibiting ERK1/2-Drp1 axis and provide a therapeutic target in diabetic vasculopathy and regenerative medicine.