Comparative analysis of mitochondrial and mesenchymal stem cell transplantation for angiogenesis and muscle regeneration

• Published in: Cell transplantation Vol. 34; p. 9636897251347391
• Main Authors: Kim, Mi Jin, Hwang, Jung Wook, Yun, Chang-Koo, Lim, Ikhyun, Min, Kyunghoon, Choi, Yong-Soo
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.06.2025; Sage Publications Ltd; SAGE Publishing
• Subjects: Angiogenesis; Animals; Apoptosis; Blood flow; Caspase-3; Cell therapy; Comparative analysis; Cytochrome c; Doppler effect; Endothelial cells; Energy metabolism; Female; Hindlimb - blood supply; Ischemia; Ischemia - metabolism; Ischemia - pathology; Ischemia - therapy; Male; Mental health; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred C57BL; Mitochondria; Mitochondria - metabolism; Mitochondria - transplantation; MnSOD gene; Muscle, Skeletal - blood supply; Muscle, Skeletal - physiology; Muscles; Neovascularization, Physiologic - physiology; Oxidative phosphorylation; Oxidative Stress; Phosphorylation; Pregnancy; Protein turnover; Reactive oxygen species; Reactive Oxygen Species - metabolism; Regeneration - physiology; Stem cell transplantation; tissue regeneration; mitochondria; angiogenesis; mitochondrial transplantation; ischemia
• ISSN: 0963-6897; 1555-3892; 1555-3892
• DOI: 10.1177/09636897251347391

Mitochondrial transplantation has emerged as a promising strategy for treating ischemic diseases by restoring mitochondrial function in damaged tissues. This study investigated the therapeutic potential of mitochondria isolated from placenta-derived mesenchymal stem cells (PD-MSCs) in a murine critical limb ischemia (CLI) model. The isolated mitochondria were characterized to confirm their structural integrity, purity, and ATP production capacity before transplantation into an ischemic hindlimb. Results showed that mitochondrial transplantation significantly improved blood flow and muscle regeneration compared with MSC transplantation, as evidenced by laser Doppler perfusion imaging and histological analysis. Enhanced ATP production and increased oxidative phosphorylation complex protein levels were observed, supporting energy metabolism in ischemic conditions. Mitochondrial transplantation also reduced mitochondrial reactive oxygen species (mROS) levels and increased antioxidant enzyme expression, including SOD-2, leading to reduced oxidative stress and apoptosis, as indicated by decreased Bax, cytosolic cytochrome c, and cleaved caspase-3 levels. Furthermore, mitochondrial transplantation promoted angiogenesis and increased vascular density in ischemic muscles by enhancing endothelial cell function. Overall, PD-MSC-derived mitochondrial transplantation demonstrated proved more effective over MSC transplantation in reducing inflammation, restoring mitochondrial function, and supporting tissue recovery, highlighting its promise as an effective therapeutic approach for CLI and other ischemic conditions by directly addressing mitochondrial dysfunction and overcoming the limitations of conventional cell therapies. Graphical Abstract