Mesenchymal stem cells rescue injured endothelial cells in an in vitro ischemia-reperfusion model via tunneling nanotube like structure-mediated mitochondrial transfer.
Mesenchymal stem cells can be used as a novel treatment of ischemic vascular disease; however, their therapeutic effect and mechanism of action require further evaluation. Mitochondrial dysfunction has core functions in ischemia-reperfusion injury of the microvascular network. A recent discovery has shown that intercellular communication using tunneling nanotubes can transfer mitochondria between adjacent cells. This study aimed to investigate the tunneling nanotube mechanisms that might be involved in stem cell-mediated mitochondrial rescue of injured vascular endothelial cells. Using laser scanning confocal microscopy, mitochondrial transfer via a tunneling nanotube-like structure was detected between mesenchymal stem cells and human umbilical vein endothelial cells. Oxygen glucose deprivation and reoxygenation were performed on human umbilical vein endothelial cells, which induced mitochondrial transfer through tunneling nanotube-like structures to become frequent and almost unidirectional from mesenchymal stem cells to injured endothelial cells, thereby resulting in the rescue of aerobic respiration and protection of endothelial cells from apoptosis. We found that the formation of tunneling nanotube-like structures might represent a defense and rescue mechanism through phosphatidylserines exposed on the surface of apoptotic endothelial cells and stem cell recognition. Our data provided evidence that stem cells can rescue damaged vascular endothelial cells through a mechanism that has not yet been identified.
Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong, China; Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Key Laboratory for Experimental Teratology of the Ministry of Education, Brain Science Research Institute, Shandong University, Jinan, Shandong, China.
Kaiming
K
Liu
Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Key Laboratory for Experimental Teratology of the Ministry of Education, Brain Science Research Institute, Shandong University, Jinan, Shandong, China.
Kunqian
K
Ji
Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Liang
L
Guo
Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Wei
W
Wu
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Huixia
H
Lu
Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Peiyan
P
Shan
Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Key Laboratory for Experimental Teratology of the Ministry of Education, Brain Science Research Institute, Shandong University, Jinan, Shandong, China. Electronic address: chuanzhuyan@163.com.
Chuanzhu
C
Yan
D017209:Apoptosis; D002450:Cell Communication / Q000502:physiology; D018920:Coculture Techniques; D004272:DNA, Mitochondrial / Q000235:genetics; D042783:Endothelial Cells / Q000473:pathology* / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000473:pathology* / Q000502:physiology*; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000473:pathology* / Q000502:physiology*; D008954:Models, Biological; D043942:Nanotubes / Q000648:ultrastructure; D010101:Oxygen Consumption; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology*
D004272:DNA, Mitochondrial; D010718:Phosphatidylserines