Kim Mi Jin, Hwang Jung Wook, Yun Chang-Koo, Lim Ikhyun, Min Kyunghoon, Choi Yong-Soo
Department of Biotechnology, CHA University, Seongnam-si, Republic of Korea.
Department of Bio Convergence Science, Graduate School, CHA University, Seongnam-si, Republic of Korea.
Cell Transplant. 2025 Jan-Dec;34:9636897251347391. doi: 10.1177/09636897251347391. Epub 2025 Jun 12.
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.
线粒体移植已成为一种通过恢复受损组织中的线粒体功能来治疗缺血性疾病的有前景的策略。本研究在小鼠严重肢体缺血（CLI）模型中研究了从胎盘来源的间充质干细胞（PD-MSCs）分离的线粒体的治疗潜力。在将分离的线粒体移植到缺血后肢之前，对其进行了表征以确认其结构完整性、纯度和ATP产生能力。结果表明，与MSC移植相比，线粒体移植显著改善了血流和肌肉再生，激光多普勒灌注成像和组织学分析证明了这一点。观察到ATP产生增强和氧化磷酸化复合蛋白水平增加，支持缺血条件下的能量代谢。线粒体移植还降低了线粒体活性氧（mROS）水平并增加了抗氧化酶表达，包括SOD-2，导致氧化应激和细胞凋亡减少，Bax、细胞色素c和裂解的caspase-3水平降低表明了这一点。此外，线粒体移植通过增强内皮细胞功能促进了缺血肌肉中的血管生成并增加了血管密度。总体而言，PD-MSC来源的线粒体移植在减少炎症、恢复线粒体功能和支持组织恢复方面比MSC移植更有效，突出了其作为CLI和其他缺血性疾病的有效治疗方法的前景，通过直接解决线粒体功能障碍并克服传统细胞疗法的局限性。
