Sanz-Ros Jorge, Huete-Acevedo Javier, Mas-Bargues Cristina, Romero-García Nekane, Dromant Mar, van Weeghel Michel, Janssens Georges E, Borrás Consuelo
MiniAging Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, CIBERFES, INCLIVA, Avenida Blasco Ibáñez, 15, Valencia, Spain.
Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Stem Cell Res Ther. 2025 Mar 13;16(1):138. doi: 10.1186/s13287-025-04255-z.
Aging entails a progressive decline in physiological functions, elevating the risk of age-related diseases like heart failure or aortic stenosis. Stem cell therapies, especially those that use paracrine signaling, can potentially mitigate the adverse effects of aging.
The objective is to explore the potential of small extracellular vesicles (sEVs) derived from young adipose-derived stem cells (ADSC-sEVs) in reversing structural, molecular, and functional changes associated with aging in the heart.
Aged C57BL/6J mice were treated intravenously with ADSC-sEVs from young mice or PBS as controls. Young mice were included to identify specific age-associated changes. The impact of sEV treatment on cardiac function was assessed using transthoracic echocardiography and physical endurance tests. Histological and molecular analyses were conducted on heart tissue to evaluate structural changes and markers of senescence, inflammation, and oxidative stress. A comprehensive metabolomic analysis was also performed on heart tissues to identify changes in metabolic profiles associated with aging and treatment status.
The administration of ADSC-sEVs significantly improves several aging-associated cardiac parameters, including oxidative stress, inflammation, and cellular senescence reductions. We also report on the age-related reversal of myocardial structure and function changes, highlighted by decreased fibrosis and improved vascularization. Notably, echocardiographic assessments reveal that sEV treatments ameliorate diastolic dysfunction and left ventricle structural alterations typically associated with aging. Furthermore, the treatment shifts the heart metabolome towards a more youthful profile.
These results denote the potential of ADSC-sEVs as a novel, noninvasive therapeutic strategy for mitigating cardiac aging-associated functional decline.
衰老会导致生理功能逐渐衰退，增加患心力衰竭或主动脉瓣狭窄等与年龄相关疾病的风险。干细胞疗法，尤其是那些利用旁分泌信号的疗法，有可能减轻衰老的不利影响。
探讨源自年轻脂肪干细胞的小细胞外囊泡（ADSC-sEVs）在逆转与心脏衰老相关的结构、分子和功能变化方面的潜力。
将老年C57BL/6J小鼠通过静脉注射来自年轻小鼠的ADSC-sEVs或作为对照的PBS进行治疗。纳入年轻小鼠以确定特定的与年龄相关的变化。使用经胸超声心动图和体能耐力测试评估sEV治疗对心脏功能的影响。对心脏组织进行组织学和分子分析，以评估结构变化以及衰老、炎症和氧化应激的标志物。还对心脏组织进行了全面的代谢组学分析，以确定与衰老和治疗状态相关的代谢谱变化。
ADSC-sEVs的给药显著改善了几个与衰老相关的心脏参数，包括氧化应激、炎症减轻和细胞衰老减少。我们还报告了心肌结构和功能变化与年龄相关的逆转，其表现为纤维化减少和血管生成改善。值得注意的是，超声心动图评估显示，sEV治疗改善了通常与衰老相关的舒张功能障碍和左心室结构改变。此外，治疗使心脏代谢组向更年轻的状态转变。
这些结果表明ADSC-sEVs作为一种减轻与心脏衰老相关的功能衰退的新型非侵入性治疗策略具有潜力。
