Nernekli Kerem, Mangarova Dilyana B, Suryadevara Vidyani, Hajipour Mohammadjavad, Tang Jian-Hong, Wang Jie, Liang Tie, Harris Marek, Ueyama Tsuyoshi, Lyons Jennifer K, Moseley Michael E, Roudi Raheleh, Pisani Laura, von Krüchten Ricarda, Duwa Ramesh, Lu-Liang Sarah Ying, Shokri Varniab Zahra, Vasyliv Iryna, Das Neeladrisingha, Murayama Masatoshi, Shinohara Issei, Pratx Guillem, Goodman Stuart B, Meade Thomas J, Daldrup-Link Heike E
Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305 USA.
Department of Chemistry, Molecular Biosciences, Neurobiology and Radiology, Northwestern University, Evanston, IL 60208 USA.
Npj Imaging. 2025;3(1):18. doi: 10.1038/s44303-025-00078-y. Epub 2025 May 3.
Senescent cells promote osteoarthritis progression through the secretion of inflammatory mediators. Preclinical studies have identified senescence-associated beta-galactosidase (β-gal) as a biomarker of senescence, but in vivo detection remains challenging. Here, we evaluated whether a β-gal responsive gadolinium (Gd) chelate can non-invasively detect β-gal expressing senescent cells with standard clinical magnetic resonance imaging (MRI) technology in vitro, ex vivo, and in vivo in porcine joints. In vitro studies showed that senescent mesenchymal stromal cells (MSCs) exhibited significant MRI signal enhancement upon incubation with the β-gal responsive Gd-chelate compared to viable control cells. In vivo, intraarticular injection of the probe into pig knee joints revealed its retention and activation by senescent cells in cartilage defects, evidenced by a significant increase in relaxation rate. MRI-based senescent cell detection holds promise for identifying patients amenable to senolytic therapies, tailoring treatment plans, and monitoring therapy response in real-time.
衰老细胞通过分泌炎症介质促进骨关节炎进展。临床前研究已将衰老相关β-半乳糖苷酶（β-gal）鉴定为衰老的生物标志物，但体内检测仍然具有挑战性。在此，我们评估了一种β-gal响应性钆（Gd）螯合物是否能够利用标准临床磁共振成像（MRI）技术在体外、离体以及猪关节体内非侵入性地检测表达β-gal的衰老细胞。体外研究表明，与活的对照细胞相比，衰老的间充质基质细胞（MSC）在与β-gal响应性Gd螯合物孵育后表现出显著的MRI信号增强。在体内，将探针关节内注射到猪膝关节中显示其在软骨缺损处被衰老细胞保留并激活，这通过弛豫率的显著增加得以证明。基于MRI的衰老细胞检测有望用于识别适合衰老细胞溶解疗法的患者、制定个性化治疗方案以及实时监测治疗反应。
