MRI detection of senescent cells in porcine knee joints with a β-galactosidase responsive Gd-chelate
Abstract 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-ga...
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Nature Portfolio
2025-05-01
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| Series: | npj Imaging |
| Online Access: | https://doi.org/10.1038/s44303-025-00078-y |
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| author | Kerem Nernekli Dilyana B. Mangarova Vidyani Suryadevara Mohammadjavad Hajipour Jian-Hong Tang Jie Wang Tie Liang Marek Harris Tsuyoshi Ueyama Jennifer K. Lyons Michael E. Moseley Raheleh Roudi Laura Pisani Ricarda von Krüchten Ramesh Duwa Sarah Ying Lu-Liang Zahra Shokri Varniab Iryna Vasyliv Neeladrisingha Das Masatoshi Murayama Issei Shinohara Guillem Pratx Stuart B. Goodman Thomas J. Meade Heike E. Daldrup-Link |
| author_facet | Kerem Nernekli Dilyana B. Mangarova Vidyani Suryadevara Mohammadjavad Hajipour Jian-Hong Tang Jie Wang Tie Liang Marek Harris Tsuyoshi Ueyama Jennifer K. Lyons Michael E. Moseley Raheleh Roudi Laura Pisani Ricarda von Krüchten Ramesh Duwa Sarah Ying Lu-Liang Zahra Shokri Varniab Iryna Vasyliv Neeladrisingha Das Masatoshi Murayama Issei Shinohara Guillem Pratx Stuart B. Goodman Thomas J. Meade Heike E. Daldrup-Link |
| author_sort | Kerem Nernekli |
| collection | DOAJ |
| description | Abstract 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 R 1 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. |
| format | Article |
| id | doaj-art-218ed68df1fd4931a549c2dbd700d265 |
| institution | OA Journals |
| issn | 2948-197X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Imaging |
| spelling | doaj-art-218ed68df1fd4931a549c2dbd700d2652025-08-20T02:11:23ZengNature Portfolionpj Imaging2948-197X2025-05-013111110.1038/s44303-025-00078-yMRI detection of senescent cells in porcine knee joints with a β-galactosidase responsive Gd-chelateKerem Nernekli0Dilyana B. Mangarova1Vidyani Suryadevara2Mohammadjavad Hajipour3Jian-Hong Tang4Jie Wang5Tie Liang6Marek Harris7Tsuyoshi Ueyama8Jennifer K. Lyons9Michael E. Moseley10Raheleh Roudi11Laura Pisani12Ricarda von Krüchten13Ramesh Duwa14Sarah Ying Lu-Liang15Zahra Shokri Varniab16Iryna Vasyliv17Neeladrisingha Das18Masatoshi Murayama19Issei Shinohara20Guillem Pratx21Stuart B. Goodman22Thomas J. Meade23Heike E. Daldrup-Link24Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineDepartment of Chemistry, Molecular Biosciences, Neurobiology and Radiology, Northwestern UniversityMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineDivision of Cardiovascular Medicine, Stanford University School of MedicineDivision of Cardiovascular Medicine, Stanford University School of MedicineMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineDepartment of Radiation Oncology and Medical Physics, Stanford UniversityDepartment of Orthopaedic Surgery, Stanford UniversityDepartment of Orthopaedic Surgery, Stanford UniversityDepartment of Radiation Oncology and Medical Physics, Stanford UniversityDepartment of Orthopaedic Surgery, Stanford UniversityDepartment of Chemistry, Molecular Biosciences, Neurobiology and Radiology, Northwestern UniversityMolecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford University School of MedicineAbstract 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 R 1 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.https://doi.org/10.1038/s44303-025-00078-y |
| spellingShingle | Kerem Nernekli Dilyana B. Mangarova Vidyani Suryadevara Mohammadjavad Hajipour Jian-Hong Tang Jie Wang Tie Liang Marek Harris Tsuyoshi Ueyama Jennifer K. Lyons Michael E. Moseley Raheleh Roudi Laura Pisani Ricarda von Krüchten Ramesh Duwa Sarah Ying Lu-Liang Zahra Shokri Varniab Iryna Vasyliv Neeladrisingha Das Masatoshi Murayama Issei Shinohara Guillem Pratx Stuart B. Goodman Thomas J. Meade Heike E. Daldrup-Link MRI detection of senescent cells in porcine knee joints with a β-galactosidase responsive Gd-chelate npj Imaging |
| title | MRI detection of senescent cells in porcine knee joints with a β-galactosidase responsive Gd-chelate |
| title_full | MRI detection of senescent cells in porcine knee joints with a β-galactosidase responsive Gd-chelate |
| title_fullStr | MRI detection of senescent cells in porcine knee joints with a β-galactosidase responsive Gd-chelate |
| title_full_unstemmed | MRI detection of senescent cells in porcine knee joints with a β-galactosidase responsive Gd-chelate |
| title_short | MRI detection of senescent cells in porcine knee joints with a β-galactosidase responsive Gd-chelate |
| title_sort | mri detection of senescent cells in porcine knee joints with a β galactosidase responsive gd chelate |
| url | https://doi.org/10.1038/s44303-025-00078-y |
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