(W1085) STRETCHING IN STEM CELL GYM MODULATES MITOCHONDRIAL DYNAMICS AND ENERGY METABOLISM TO INDUCE SMOOTH MUSCLE DIFFERENTIATION IN MESENCHYMAL STEM CELLS
Abstract: The smooth muscle cells (SMCs) located in the vascular media layer are continuously subjected to cyclic stretching perpendicular to the vessel wall and play a crucial role in vascular wall remodeling and blood pressure regulation. Construction of bioengineered blood vessels requires regeneration of functional SMC layer to withstand the different magnitudes of blood pressure. However, the quantity of SMCs isolated from natural vessels is insufficient, and their proliferative capacity is limited. Mesenchymal stem cells (MSCs) are promising tools to differentiate into SMCs. We are inspired by the notion that stretching exercises in gyms can stimulate muscle cell metabolism, improve muscle contractility, and thereby accelerating muscle repair processes. Therefore, we design a stem cell stretching program, like training the stem cell in the gym, which induces the expression of SMC markers α-SMA and SM22 in MSCs. These cells exhibited contractile ability in vitro and facilitated vascular structure formation in the Matrigel plug assay in vivo. The contraction of SMCs requires remodeling of their energy metabolism. However, the underlying mechanism remains to be revealed. Our study shows that stretch training promotes glycolysis, oxidative phosphorylation, and mitochondrial fusion, thereby contributing to MSCs differentiation. Yes-associated protein (YAP) affects mitochondrial dynamics, oxidative phosphorylation, and glycolysis to regulate stretch-mediated differentiation into SMCs. Additionally, Piezo-type mechanosensitive ion channel component 1 (Piezo1) impacts energy metabolism and MSCs differentiation by regulating intracellular Ca2+ levels and YAP nuclear localization. Therefore, our findings indicate that YAP can integrate stretch force and energy metabolism signals to regulate the differentiation of MSCs into SMCs. It provides a scientific foundation for future vascular tissue engineering with MSCs.
Funding Source: BNSF [L242125, L234072, L242042]. National Natural Science Foundation of China [ 32171310, 12472315, U20A20390, 12332019]; The Fundamental Research Funds for the Central Universities.SKLOD2024OF01
