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MRI detection of senescent cells in porcine knee joints with a β-galactosidase responsive Gd-chelate.

作者信息

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

机构信息

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.

出版信息

Npj Imaging. 2025;3(1):18. doi: 10.1038/s44303-025-00078-y. Epub 2025 May 3.


DOI:10.1038/s44303-025-00078-y
PMID:40330124
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12049270/
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 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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dda/12118744/2a2cb4d06475/44303_2025_78_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dda/12118744/cb7202fe3933/44303_2025_78_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dda/12118744/d648e34b9d25/44303_2025_78_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dda/12118744/296475afa7d7/44303_2025_78_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dda/12118744/dedc0c513a59/44303_2025_78_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dda/12118744/34ebcfe1225b/44303_2025_78_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dda/12118744/2a2cb4d06475/44303_2025_78_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dda/12118744/cb7202fe3933/44303_2025_78_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dda/12118744/d648e34b9d25/44303_2025_78_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dda/12118744/296475afa7d7/44303_2025_78_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dda/12118744/dedc0c513a59/44303_2025_78_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dda/12118744/34ebcfe1225b/44303_2025_78_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dda/12118744/2a2cb4d06475/44303_2025_78_Fig6_HTML.jpg

相似文献

[1]
MRI detection of senescent cells in porcine knee joints with a β-galactosidase responsive Gd-chelate.

Npj Imaging. 2025

[2]
Cellular senescence imaging and senolysis monitoring in cancer therapy based on a β-galactosidase-activated aggregation-induced emission luminogen.

Acta Biomater. 2024-4-15

[3]
Clearance of senescent cells with ABT-263 improves biological functions of synovial mesenchymal stem cells from osteoarthritis patients.

Stem Cell Res Ther. 2022-6-3

[4]
Characterization of Induction and Targeting of Senescent Mesenchymal Stromal Cells.

Tissue Eng Part C Methods. 2022-6

[5]
β-Gal gene expression MRI reporter in melanoma tumor cells. Design, synthesis, and in vitro and in vivo testing of a Gd(III) containing probe forming a high relaxivity, melanin-like structure upon β-Gal enzymatic activation.

Bioconjug Chem. 2011-11-15

[6]
(1-(2-(β-Galactopyranosyloxy)propyl)-4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) gadolinium(III)

2004

[7]
Gadolinium Magnetic Resonance Imaging

2025-1

[8]
Synthesis and characterization of a cell-permeable bimodal contrast agent targeting β-galactosidase.

Bioorg Med Chem. 2011-3-13

[9]
Far-red Fluorescent Senescence-associated β-Galactosidase Probe for Identification and Enrichment of Senescent Tumor Cells by Flow Cytometry.

J Vis Exp. 2022-9-13

[10]
A dual-enzyme activated fluorescent probe for precise identification of tumor senescence.

Chem Sci. 2025-3-11

本文引用的文献

[1]
SenNet recommendations for detecting senescent cells in different tissues.

Nat Rev Mol Cell Biol. 2024-12

[2]
Lifestyle behaviour changes associated with osteoarthritis: a prospective cohort study.

Sci Rep. 2024-3-14

[3]
Novel Clinically Translatable Iron Oxide Nanoparticle for Monitoring Anti-CD47 Cancer Immunotherapy.

Invest Radiol. 2024-5-1

[4]
SSR white paper: guidelines for utilization and performance of direct MR arthrography.

Skeletal Radiol. 2024-2

[5]
Efficient secreted expression of natural intracellular β-galactosidase from Bacillus aryabhattai via non-classical protein secretion pathway in Bacillus subtilis.

Int J Biol Macromol. 2023-9-1

[6]
Spatial mapping of cellular senescence: emerging challenges and opportunities.

Nat Aging. 2023-7

[7]
Author Correction: Senescent cardiomyocytes contribute to cardiac dysfunction following myocardial infarction.

NPJ Aging. 2023-6-23

[8]
MegaPro, a clinically translatable nanoparticle for tracking of stem cell implants in pig cartilage defects.

Theranostics. 2023

[9]
Molecular Engineering of Self-Immolative Bioresponsive MR Probes.

J Am Chem Soc. 2023-5-10

[10]
NIH SenNet Consortium to map senescent cells throughout the human lifespan to understand physiological health.

Nat Aging. 2022-12

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