Mitochondrial Function Changes in hiPSCs-Derived Vascular Smooth Muscle Cells

Abstract

Utilizing human-induced pluripotent stem-cell-derived vascular smooth muscle cells (hiPSC-VSMCs) to address seed cell source in tissue-engineered vascular grafts necessitates promoting cellular maturation. Morphological changes and functional remodeling of mitochondria are crucial to cellular differentiation and maturation. However, our current understanding of these changes during the transition from hiPSCs to VSMCs is limited. Our findings revealed that after hiPSC-VSMC differentiation, mitochondria transitioned from perinuclear to cytoplasmic distribution, increased in number, and changed shape to elongated tubular structures with uniform matrix density. Transcriptomic data indicated upregulation of genes related to mitochondrial fusion, autophagy, and electron transport chain post differentiation. Additionally, the intracellular ATP content was increased, suggestive of increased bioenergetic capacity. Integrated multiomics analysis revealed signatures indicative of activated mitochondrial oxidative metabolism, including tricarboxylic acid cycle, oxidative phosphorylation, fatty acid oxidation, and amino acid catabolism pathways. The study aims to investigate morphological and functional changes of mitochondria during hiPSC-VSMC differentiation, providing a basis for further optimizing differentiation protocols.