Changes, and the Relevance Thereof, in Mitochondrial Morphology during Differentiation into Endothelial Cells

• Published in: PloS one 2016-08, Vol.11 (8), p.e0161015-e0161015
• Main Authors: Shin, Ji Won, Park, So Hee, Kang, Yun Gyeong, Wu, Yanru, Choi, Hyun Ju, Shin, Jung-Woog
• Format: Article
• Language: English
• Subjects: Biology and Life Sciences; Biomedical engineering; Biosynthesis; Cell Differentiation; Cytology; Data processing; Diabetes; Diabetic retinopathy; Differentiation (biology); Dosage and administration; Endothelial cells; Endothelial Cells - cytology; Endothelium; Energy; Engineering; Form factors; Gene expression; Glucose; Growth factors; Humans; Medicine and Health Sciences; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchyme; Mitochondria; Mitochondria - metabolism; Mitochondrial DNA; Mitochondrial Size; Morphology; Phase transitions; Physical Sciences; Physiological aspects; Physiology; Quantitative analysis; R&D; Research & development; Research and Analysis Methods; Reynolds number; Shear Strength; Shear stress; Stem cells; Stress, Mechanical; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Von Willebrand factor
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0161015

The roles of mitochondria in various physiological functions of vascular endothelial cells have been investigated extensively. Morphological studies in relation to physiological functions have been performed. However, there have been few reports of morphological investigations related to stem cell differentiation. This was the first morphological study of mitochondria in relation to endothelial differentiation and focused on quantitative analysis of changes in mitochondrial morphology, number, area, and length during differentiation of human mesenchymal stem cells (hMSCs) into endothelial-like cells. To induce differentiation, we engaged vascular endothelial growth factors and flow-induced shear stress. Cells were classified according to the expression of von Willebrand factor as hMSCs, differentiating cells, and almost fully differentiated cells. Based on imaging analysis, we investigated changes in mitochondrial number, area, and length. In addition, mitochondrial networks were quantified on a single-mitochondrion basis by introducing a branch form factor. The data indicated that the mitochondrial number, area per cell, and length were decreased with differentiation. The mitochondrial morphology became simpler with progression of differentiation. These findings could be explained in view of energy level during differentiation; a higher level of energy is needed during differentiation, with larger numbers of mitochondria with branches. Application of this method to differentiation into other lineages will explain the energy levels required to control stem cell differentiation.