Magnetic Resonance Imaging of Chondrocytes Labeled with Superparamagnetic Iron Oxide Nanoparticles in Tissue-Engineered Cartilage

Ramaswamy, Sharan; Greco, Jane B.; Uluer, Mehmet C.; Zhang, Zijun; Zhang, Zhuoli; Fishbein, Kenneth W.; Spencer, Richard G.

doi:10.1089/ten.tea.2008.0677

Cited by 67 publications

(51 citation statements)

References 50 publications

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“…96 SPIO-labeled chondrocytes were also shown to maintain their phenotype and to continue the production of cartilage-specific ECM components in hollow-fiber bioreactor experiments or when grown in alginate beads. [95][96][97] It was also confirmed that the chondrocyte differentiation of human bone marrow-derived MSCs seeded in porcine osteochondral plugs was not affected by SPIO labeling in vitro and this strategy can be used for MRI cell tracking in cartilage tissue engineering effectively. 98 Chen et al 99 observed optimal low-dosage SPIOlabeled cells in a minipig model and found that the labeled cells could be tracked for at least 12 weeks using T 2 -weighted MR imaging.…”

Section: Magnetic Resonance Imagingmentioning

confidence: 68%

“…One way to observe these cells is to label them with superparamagnetic iron oxide (SPIO) particles. SPIO particles were used for tracking chondrocytes grown in agarose by Ramaswamy et al 95 for an incubation time of 6 weeks. In another study, the T 2 values of SPIO-labeled cells were found to decrease with the increasing cell number, which can be used as a signal contrast standard for labeled cells.…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

“…Recent 7-week studies of chondrocytes growing in an MRcompatible hollow cylinder bioreactor tracked the development of new cartilage-like tissue using T 2 relaxation times and SPIO nanoparticles. 93,95 Alternatively, in vivo imaging of small animal models (e.g., SCID mice, rats, and rabbits) can be performed weekly to test the efficacy of tissue-engineering strategies, often using narrow bore (20-30 cm) high field (4.7-11 Tesla) animal MRI systems. Large animals (e.g., dogs, goats, pigs, and horses) have also been used for cartilage repair studies, 127 but they present challenges as clinical MR scanners must be used in most cases.…”

Section: In Vivo Mr Techniques For Monitoring Of Cartilage Tissue Engmentioning

confidence: 99%

See 2 more Smart Citations

Monitoring Cartilage Tissue Engineering Using Magnetic Resonance Spectroscopy, Imaging, and Elastography

Kotecha

Klatt

Magin

2013

Tissue Engineering Part B: Reviews

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A key technical challenge in cartilage tissue engineering is the development of a noninvasive method for monitoring the composition, structure, and function of the tissue at different growth stages. Due to its noninvasive, three-dimensional imaging capabilities and the breadth of available contrast mechanisms, magnetic resonance imaging (MRI) techniques can be expected to play a leading role in assessing engineered cartilage. In this review, we describe the new MR-based tools (spectroscopy, imaging, and elastography) that can provide quantitative biomarkers for cartilage tissue development both in vitro and in vivo. Magnetic resonance spectroscopy can identify the changing molecular structure and alternations in the conformation of major macromolecules (collagen and proteoglycans) using parameters such as chemical shift, relaxation rates, and magnetic spin couplings. MRI provides high-resolution images whose contrast reflects developing tissue microstructure and porosity through changes in local relaxation times and the apparent diffusion coefficient. Magnetic resonance elastography uses low-frequency mechanical vibrations in conjunction with MRI to measure soft tissue mechanical properties (shear modulus and viscosity). When combined, these three techniques provide a noninvasive, multiscale window for characterizing cartilage tissue growth at all stages of tissue development, from the initial cell seeding of scaffolds to the development of the extracellular matrix during construct incubation, and finally, to the postimplantation assessment of tissue integration in animals and patients.

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Section: Magnetic Resonance Imagingmentioning

confidence: 68%

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

Section: In Vivo Mr Techniques For Monitoring Of Cartilage Tissue Engmentioning

confidence: 99%

See 1 more Smart Citation

Monitoring Cartilage Tissue Engineering Using Magnetic Resonance Spectroscopy, Imaging, and Elastography

Kotecha

Klatt

Magin

2013

Tissue Engineering Part B: Reviews

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“…15,33 Recently, to improve contrast in MRI, a Food and Drug Administration-approved superparamagnetic iron oxide contrast agent (Feridex) was used to label chondrocytes and observe the presence of individual cells in tissue-engineered cartilage constructs. 34 Such information is vital to staging and assessing tissue development.…”

Section: Discussionmentioning

confidence: 99%

Magnetization Transfer Imaging Provides a Quantitative Measure of Chondrogenic Differentiation and Tissue Development

Hong

et al. 2010

Tissue Engineering Part C: Methods

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The goal of the present investigation was to test whether quantitative magnetization transfer imaging can be used as a noninvasive evaluation method for engineered cartilage. In this work, we used magnetic resonance imaging (MRI) to monitor the chondrogenesis of stem-cell-based engineered tissue over a 3-week period by measuring on a pixel-by-pixel basis the relaxation times (T 1 and T 2 ), the apparent diffusion coefficient, and the magnetization transfer parameters: bound proton fraction and cross-relaxation rate (k). Tissue-engineered constructs for generating cartilage were created by seeding mesenchymal stem cells in a gelatin sponge. Every 7 days, tissue samples were analyzed using MRI, histological, and biochemical methods. The MRI measurements were verified by histological analysis, and the imaging data were correlated with biochemical analysis of the developing cartilage matrix for glycosaminoglycan content. The MRI analysis for bound proton fraction and k showed a statistically significant increase that was correlated with the increase of glycosaminoglycan (R ¼ 0.96 and 0.87, respectively, p < 0.05), whereas T 1 , T 2 , and apparent diffusion coefficient results did not show any significant changes over the 3-week measurement period.

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“…Magnetic Resonance Spectroscopy (MRS or NMR as it is known widely) and Magnetic Resonance Imaging (MRI) are increasingly used in tissue engineering laboratories as new non-invasive characterization tools for the engineered tissues [19][20][21][22][23][24][25][26]. MRS is an established technique to investigate the atomic level structure and molecular dynamics of biological samples, whereas MRI provides volumetric maps of tissue based on the spin density, relaxation times, or diffusion of water protons or other high abundance NMR visible nuclei (such as sodium in cartilage tissue and phosphorous in bone tissue) [27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Monitoring Tissue Engineering and Regeneration by Magnetic Resonance Imaging and Spectroscopy

Kotecha¹

2012

J Tissue Sci Eng

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In this article, based on the invited talk at the "Tissue Science 2012" meeting in Chicago on October 1-3, 2012, we describe some examples of characterization of engineered cartilage and bone tissue using magnetic resonance spectroscopy and imaging. Two different models of engineered cartilage and engineered bone tissue constructs were used for these studies: 1) chondrocyte based cartilage tissue engineering constructs: human and bovine chondrocytes seeded in alginate beads (Hydrogel scaffold model) or bovine chondrocytes grown as pellets (scaffold free model); 2) mesenchymal stem cell (MSC) based cartilage and bone tissue engineering constructs: human mesenchymal stem cell (HMSCs) seeded in cartilage biomimetic scaffolds (collagen/chitosan scaffold integrated with extracellular matrix of cartilage) or HMSCs seeded in collagen/chitosan scaffolds. Magnetic resonance spectroscopy and imaging experiments using 9.4 T (400 MHz proton frequency), 11.7 T (500 MHz proton frequency) or 14.1 T (600 MHz proton frequency) MR spectrometers/Imager were performed on these constructs over two to four weeks of tissue culture time. Specifically, water suppressed proton NMR spectroscopy; proton and sodium multi-quantum coherence spectroscopy and proton T1, T2 and ADC parametric MRI were used to study the chondrogenesis and osteogenesis of these tissues. We found that the change in MR relaxation and diffusion coefficient parameters correlate well with the growth of engineered tissues. We found that the MR parameters and the change in these parameters in growing tissue are strongly influenced by the choice of scaffolds. We also found as expected that the tissue-engineered cartilage lacked order or preference in collagen orientation. Further work is underway to elucidate these findings. We anticipate that in future, MRI will augment histological and immunohistochemical techniques by providing a complimentary and real time quantitative assessment of engineered tissue growth at all growth stages: (i) cell seeding to pre implantation; (ii) preclinical validation studies post implantation in small and large animal models; (iii) clinical studies of performance of engineered tissues.

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Magnetic Resonance Imaging of Chondrocytes Labeled with Superparamagnetic Iron Oxide Nanoparticles in Tissue-Engineered Cartilage

Cited by 67 publications

References 50 publications

Monitoring Cartilage Tissue Engineering Using Magnetic Resonance Spectroscopy, Imaging, and Elastography

Monitoring Cartilage Tissue Engineering Using Magnetic Resonance Spectroscopy, Imaging, and Elastography

Magnetization Transfer Imaging Provides a Quantitative Measure of Chondrogenic Differentiation and Tissue Development

Monitoring Tissue Engineering and Regeneration by Magnetic Resonance Imaging and Spectroscopy

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