MRI detection of senescent cells in porcine knee joints with a β-galactosidase responsive Gd-chelate
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 <i>R</i> <sub>1</sub> 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.
Authors
- Heike Elisabeth Daldrup-Link (ORCID: https://orcid.org/0000-0002-4929-819X)
- Issei Shinohara (ORCID: https://orcid.org/0000-0002-4122-7119)
- Neeladrisingha Das (ORCID: https://orcid.org/0000-0001-5394-0432)
- Kerem Nernekli (ORCID: https://orcid.org/0000-0001-8586-3494)
- Vidyani Suryadevara
- Dilyana B. Mangarova (ORCID: https://orcid.org/0000-0001-5954-3710)
- Stuart B. Goodman (ORCID: https://orcid.org/0000-0002-1919-3717)
- Jian‐Hong Tang (ORCID: https://orcid.org/0000-0002-3299-5167)
- Zahra Shokri Varniab (ORCID: https://orcid.org/0000-0002-2121-6658)
- Michael E. Moseley (ORCID: https://orcid.org/0000-0002-9163-8741)
- Ramesh Duwa (ORCID: https://orcid.org/0000-0001-9862-4425)
- Laura Pisani (ORCID: https://orcid.org/0000-0003-3084-3300)
- Masatoshi Murayama (ORCID: https://orcid.org/0009-0000-1228-482X)
- Guillem Pratx (ORCID: https://orcid.org/0000-0002-0247-6470)
- Raheleh Roudi (ORCID: https://orcid.org/0000-0001-5023-4743)
- Thomas J. Meade (ORCID: https://orcid.org/0000-0001-6202-1155)
- Iryna Vasyliv
- Tsuyoshi Ueyama
- Jiannong Wang (ORCID: https://orcid.org/0000-0002-6133-6371)
- Jennifer Lyons
- Tie Liang
- Mary Harris
- Mohammadjavad Hajipour
- Sarah Ying Lu-Liang
- Ricarda von Krüchten
Institutions
- Stanford University (US)
Publication Details
- Journal
- npj Imaging
- Published
- 2025-05-03
- DOI
- https://doi.org/10.1038/s44303-025-00078-y
- Citations
- 3
- Primary Topic
- Telomeres, Telomerase, and Senescence
- Type
- article
- Field-Weighted Citation Impact
- 3.49
Funders
- Northwestern University
- National Institutes of Health
- Ames Research Center
- Robert H. Lurie Comprehensive Cancer Center
- National Institute of Neurological Disorders and Stroke
- National Institute of Arthritis and Musculoskeletal and Skin Diseases