True MRI assessment of stem cell chondrogenesis in a tissue engineered matrix

Pothirajan, Padmabharathi; Dorcemus, Deborah; Nukavarapu, Syam P.; Kotecha, Mrignayani

doi:10.1109/embc.2014.6944484

Cited by 7 publications

(7 citation statements)

References 18 publications

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“…This is important in order (a) to assess the efficacy of tissue engineering approaches at an early growth stage, (b) for providing an accurate assessment of engineered tissue growth postimplantation, and (c) for monitoring the healing of cartilage after treatment. Magnetic resonance imaging (MRI) is a leading non-invasive characterization technique for monitoring growth in cartilage tissue engineering [2][3][4][5][6][7]. Research Cartilage tissue in its native state contains chondrocytes (~1%) imbedded in an extracellular matrix (ECM).…”

Section: Introductionmentioning

confidence: 99%

Reduction of water diffusion coefficient with increased engineered cartilage matrix growth observed using MRI

Kotecha

Schmid

Odintsov

et al. 2014

2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society

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Non-destructive monitoring of tissue-engineered cartilage growth is needed to optimize growth conditions, but extracting quantitative biomarkers of extracellular matrix development remains a technical challenge. MRI provides a non-invasive way to obtain a three dimensional map of growing tissue where the image contrast is based on tissue water relaxation times and the apparent diffusion coefficient (ADC). In this study, bovine chondrocytes were seeded in alginate beads (0, 1, 2, and 4 million cells/ml) and the ADC was measured weekly using diffusion-weighted MRI at 14.1 T over a one-month incubation period. Two groups of tissue-engineering constructs were created: one with ascorbic acid (vitamin C) added as a vitamin cofactor to increase collagen synthesis, and another with no added ascorbic acid. When normalized to the control beads without chondrocytes, the ADC was found to monotonically fall with incubation time (decreasing by up to 40% at 4 weeks), and with the administration of vitamin C. These results reflect the expected development of the extracellular matrix in the tissue-engineered constructs. We conclude that the normalized ADC is a potential biomarker for characterizing engineered cartilage tissue growth.

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Section: Introductionmentioning

confidence: 99%

Reduction of water diffusion coefficient with increased engineered cartilage matrix growth observed using MRI

Kotecha

Schmid

Odintsov

et al. 2014

2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society

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“…= 600 MHz). These higher field strengths provide much higher resolution (~10-20 µm) images for small size (~few mm) in vitro samples 23,25,34 . The most common MRI techniques for tissue growth assessment involve the quantification of change in water proton relaxation times (T 1 and T 2 ) and water apparent diffusion coefficient (ADC) to gauge the production of proteoglycans and collagen, the two main components of the cartilage extracellular matrix.…”

Section: Introductionmentioning

confidence: 99%

High Field Sodium MRI Assessment of Stem Cell Chondrogenesis in a Tissue-Engineered Matrix

et al. 2015

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The development of non-invasive assessment techniques in vitro and in vivo is essential for monitoring and evaluating the growth of engineered cartilage tissues. Magnetic resonance imaging (MRI) is the leading non-invasive imaging modality used for assessing engineered cartilage. Typical MRI uses water proton relaxation times (T1 and T2) and apparent diffusion coefficient (ADC) to assess tissue growth. These techniques, while excellent in providing the first assurance of tissue growth, are unspecific to monitor the progress of engineered cartilage extracellular matrix components. In the current article, we present high field (11.7 T, (1)H freq. = 500 MHz) sodium MRI assessment of tissue-engineered cartilage at the early stage of tissue growth in vitro. We observed the chondrogenesis of human bone marrow derived stromal cells seeded in a gradient polymer-hydrogel matrix made out of poly(85 lactide-co-15 glycolide)--PuraMatrix™ for 4 weeks. We calculated the sodium concentration in the engineered constructs using a model of sodium MRI voxels that takes into account scaffold volume, cell density and amount of glycosaminoglycan (GAG). The sodium concentration was then converted to the fixed charge density (FCD) and compared with FCD derived from biochemical GAG analysis. Despite the small amount of GAG present in the engineered constructs, the sodium MRI derived FCD is found to be correlated (Pearson correlation coefficient R = 0.79) with the FCD derived from biochemical analysis. We conclude that sodium MRI could prove to be an invaluable tool in assessing engineered cartilage quantitatively during the repair or regeneration of cartilage defects.

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“…It is possible to track these changes if the scaffold contribution to the MR data is eliminated. We recently published on a methodology to accomplish this using MRI data obtained from scaffolds in vitro [14]. We applied this methodology to the MRI evaluations of the scaffolds in vivo .…”

Section: Resultsmentioning

confidence: 99%

“…Magnetic Resonance Imaging (MRI) is ideal for measuring the growth dynamics of cartilage tissue [12-14]. Our recent review article summarizes the development in the field of non-invasive monitoring of engineered cartilage using magnetic resonance techniques [12].…”

Section: Introductionmentioning

confidence: 99%

Biological and MRI characterization of biomimetic ECM scaffolds for cartilage tissue regeneration

et al. 2015

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Osteoarthritis is the most common joint disorder affecting millions of people. Most scaffolds developed for cartilage regeneration fail due to vascularization and matrix mineralization. In this study we present a chondrogenic extracellular matrix (ECM) incorporated collagen/chitosan scaffold (chondrogenic ECM scaffold) for potential use in cartilage regenerative therapy. Biochemical characterization showed that these scaffolds possess key pro-chondrogenic ECM components and growth factors. MRI characterization showed that the scaffolds possess mechanical properties and diffusion characteristics important for cartilage tissue regeneration. In vivo implantation of the chondrogenic ECM scaffolds with bone marrow derived mesenchymal stem cells (MSCs) triggered chondrogenic differentiation of the MSCs without the need for external stimulus. Finally, results from in vivo MRI experiments indicate that the chondrogenic ECM scaffolds are stable and possess MR properties on par with native cartilage. Based on our results, we envision that such ECM incorporated scaffolds have great potential in cartilage regenerative therapy. Additionally, our validation of MR parameters with histology and biochemical analysis indicates the ability of MRI techniques to track the progress of our ECM scaffolds non-invasively in vivo; highlighting the translatory potential of this technology.

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True MRI assessment of stem cell chondrogenesis in a tissue engineered matrix

Cited by 7 publications

References 18 publications

Reduction of water diffusion coefficient with increased engineered cartilage matrix growth observed using MRI

Reduction of water diffusion coefficient with increased engineered cartilage matrix growth observed using MRI

High Field Sodium MRI Assessment of Stem Cell Chondrogenesis in a Tissue-Engineered Matrix

Biological and MRI characterization of biomimetic ECM scaffolds for cartilage tissue regeneration

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