Mesenchymal stem cell-derived conditioned medium protects vascular grafts of brain-dead rats against in vitro ischemia/reperfusion injury

• Published in: Stem cell research & therapy 2021-02, Vol.12 (1), p.144-144, Article 144
• Main Authors: Korkmaz-Icöz, Sevil, Zhou, Pengyu, Guo, Yuxing, Loganathan, Sivakkanan, Brlecic, Paige, Radovits, Tamás, Sayour, Alex Ali, Ruppert, Mihály, Veres, Gábor, Karck, Matthias, Szabó, Gábor
• Format: Article
• Language: English
• Subjects: Acetylcholine; Acidosis; Animal experimentation; Aorta; Apoptosis; Blood pressure; Blood vessels; Bone marrow; Brain death; Brain injury; Caspase-12; Caspase-3; Caspase-8; Caspase-9; Catheters; Cell adhesion molecules; Chemokines; Conditioned medium; Coronary vessels; Cytokines; Dilatation; Endothelial function; Endothelium; Gene expression; Heart; Heart transplantation; Immunohistochemistry; Inflammation; Intercellular adhesion molecule 1; Investigations; Ischemia; Ischemia/reperfusion; Laboratory animals; Mesenchymal stem cells; Nitrotyrosine; Oxidative stress; Peroxidase; Physiological aspects; Physiology; Polymerase chain reaction; Reperfusion; Stem cells; Transplantation; Transplants & implants; Vasodilation
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-021-02166-3

Brain death (BD) has been suggested to induce coronary endothelial dysfunction. Ischemia/reperfusion (IR) injury during heart transplantation may lead to further damage of the endothelium. Previous studies have shown protective effects of conditioned medium (CM) from bone marrow-derived mesenchymal stem cells (MSCs) against IR injury. We hypothesized that physiological saline-supplemented CM protects BD rats' vascular grafts from IR injury. The CM from rat MSCs, used for conservation purposes, indicates the presence of 23 factors involved in apoptosis, inflammation, and oxidative stress. BD was induced by an intracranial-balloon. Controls were subjected to a sham operation. After 5.5 h, arterial pressures were measured in vivo. Aortic rings from BD rats were harvested and immediately mounted in organ bath chambers (BD group, n = 7) or preserved for 24 h in 4 °C saline-supplemented either with a vehicle (BD-IR group, n = 8) or CM (BD-IR+CM group, n = 8), prior to mounting. Vascular function was measured in vitro. Furthermore, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) have been performed. BD in donors was associated with significantly impaired hemodynamic parameters and higher immunoreactivity of aortic myeloperoxidase (MPO), nitrotyrosine, caspase-3, caspase-8, caspase-9, and caspase-12 compared to sham-operated rats. In organ bath experiments, impaired endothelium-dependent vasorelaxation to acetylcholine in the BD-IR group compared to BD rats was significantly improved by CM (maximum relaxation to acetylcholine: BD 81 ± 2% vs. BD-IR 50 ± 3% vs. BD-IR + CM 72 ± 2%, p