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Bioreactors for Tissue Engineering pp 335–352Cite as

Monitoring the Performance of Tissue Engineering Bioreactors Using Magnetic Resonance Imaging and Spectroscopy

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Conclusions

The NMR-based methods described here are able to evaluate local changes in cell density and metabolic activity, perfusion and flow velocities within a functional engineered tissue. The application of NMR techniques is particularly attractive in the context of bioartificial organs. The application of such techniques over the past 25 years to the study of intact biological systems, including man, has generated a wealth of data, including spectroscopic and imaging profiles of healthy and diseased tissues. This database is a valuable tool that can be used to assess the performance of cells from a given tissue, when incorporated into a bioartificial organ, and/or the physical and morphological properties of an engineered tissue as compared to its native counterpart. This approach could be useful, for example, for monitoring the progress of skin grafts, or to assess GAG and collagen contents locally in a repair site within articular or meniscal cartilage. The possibility of using the same suite of techniques both in vitro, during the production stage of the tissue, and in vivo, post implantation, is probably unique to NMR and represents a tremendous advantage of this technique.

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References

  • Adams, M.E., Li, D.K., McConkey, J.P., Davidson, R.G., Day, B., Duncan, C.P. and Tron, V. 1991. Evaluation of cartilage lesions by magnetic resonance imaging at 0.15 T: comparison with anatomy and concordance with arthroscopy. J Rheumatol. 18: 1573–1580.

    PubMed  CAS  Google Scholar 

  • Allen, J.W. and Bhatia, S.N. 2002. Improving the next generation of bioartificial liver devices. Semin Cell Dev Biol. 13: 447–54.

    Article  PubMed  CAS  Google Scholar 

  • As, H.V. and Lens, P. 2001. Use of 1H NMR to study transport processes in porous biosystems. J Ind Microbiol Biotechnol. 26: 43–52.

    Article  CAS  Google Scholar 

  • Axel, L., Shimakawa, A., MacFall, J. 1986. A time-of-flight method of measuring flow velocity by magnetic resonance imaging. Magn Reson Imaging. 4: 199–205.

    Article  PubMed  CAS  Google Scholar 

  • Bashir, A., Gray, M.L., Hartke, J. and Burstein, D. 1999. Nondestructive imaging of human cartilage glycosaminoglycan concentration by MRI. Magn Reson Med. 41: 857–65.

    Article  PubMed  CAS  Google Scholar 

  • Bashir, A., Gray, M.L., Boutin, R.D. and Burstein, D. 1997. Glycosaminoglycan in articular cartilage: in vivo assessment with delayed Gd(DTPA)(2-)-enhanced MR imaging. Radiology. 205: 551–558.

    PubMed  CAS  Google Scholar 

  • Begley, C.M. and Kleis, S.J. 2000. The fluid dynamic and shear environment in the NASA/JSC rotating-wall perfused-vessel bioreactor. Biotechnol Bioeng. 70: 32–40.

    Article  PubMed  CAS  Google Scholar 

  • Brindle, K.M. 1998. Investigating the performance of intensive mammalian cell bioreactor systems using magnetic resonance imaging and spectroscopy. Biotech Genetic Eng Rev. 15: 499–520.

    CAS  Google Scholar 

  • Brindle, K.M. 1995. Enzyme-catalyzed exchange: magnetisation transfer measurements. In: D. M. G. a. R.K. Harris editor. Encyclopedia of Nuclear Magnetic Resonance. Chichester: John Wiley and Sons Ltd. p 1902–1909.

    Google Scholar 

  • Brindle, K.M., Blackledge, M.J., Challiss, R.A. and Radda, G.K. 1989. 31P NMR magnetization-transfer measurements of ATP turnover during steady-state isometric muscle contraction in the rat hind limb in vivo. Biochemistry. 28: 4887–93.

    Article  PubMed  CAS  Google Scholar 

  • Buckwalter, J.A. and Martin, J. 1995. Degenerative joint disease. Clin Symp. 47: 1–32.

    PubMed  CAS  Google Scholar 

  • Burstein, D., Bashir, A. and Gray, M.L. 2000. MRI techniques in early stages of cartilage disease. Invest Radiol. 35: 622–38.

    Article  PubMed  CAS  Google Scholar 

  • Callies, R., Jackson, M.E. and Brindle, K.M. 1994. Measurements of the growth and distribution of mammalian cells in a hollow-fiber bioreactor using nuclear magnetic resonance imaging. Biotechnology (N Y). 12: 75–78.

    Article  CAS  Google Scholar 

  • Constantinidis, I., Stabler, C.L., Long, R., Jr. and Sambanis, A. 2002. Noninvasive monitoring of a retrievable bioartificial pancreas in vivo. Ann N Y Acad Sci. 961: 298–301.

    PubMed  Google Scholar 

  • Crank, J. 1964. The Mathematics of Diffusion. London: Oxford University Press.

    Google Scholar 

  • Dardzinski, B.J., Mosher, T.J., Li, S., Van Slyke, M.A. and Smith, M.B. 1997. Spatial variation of T2 in human articular cartilage. Radiology. 205: 546–50.

    PubMed  CAS  Google Scholar 

  • Deo, Y.M., Mahadevan, M.D. and Fuchs, R. 1996. Practical considerations in operation and scale-up of spin-filter based bioreactors for monoclonal antibody production. Biotechnol Prog. 12: 57–64.

    Article  PubMed  CAS  Google Scholar 

  • Desmoulin, F., Confort-Gouny, S., Masson, S., Bernard, M., Doddrell, D.M. and Cozzone, P.J. 1990. Application of reverse-DEPT polarization transfer pulse sequence to study the metabolism of carbon-13-labeled substrates in perfused organs by 1H NMR spectroscopy. Magn Reson Med. 15: 456–61.

    PubMed  CAS  Google Scholar 

  • Donoghue, C., Brideau, M., Newcomer, P., Pangrle, B., DiBiasio, D., Walsh, E. and Moore, S. 1992. Use of magnetic resonance imaging to analyze the performance of hollow-fiber bioreactors. Ann N Y Acad Sci. 665: 285–300.

    PubMed  CAS  Google Scholar 

  • Farndale, R.W., Buttle, D.J. and Barrett, A.J. 1986. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta. 883: 173–7.

    PubMed  CAS  Google Scholar 

  • Fernandez, E.J., Mancuso, A. and Clark, D.S. 1988. NMR spectroscopy studies of hybridoma metabolism in a simple membrane bioreactor. Biotechnol Progress. 4: 173–83.

    CAS  Google Scholar 

  • Foy, B.D. and Blake, J. 2001. Diffusion of paramagnetically labeled proteins in cartilage: Enhancement of the 1-D NMR imaging technique. J Magn Reson. 148: 126–134.

    Article  PubMed  CAS  Google Scholar 

  • Franks, S.E., Kuesel, A.C., Lutz, N.W. and Hull, W.E. 1996. 31P MRS of human tumor cells: effects of culture media and conditions on phospholipid metabolite concentrations. Anticancer Res. 16: 1365–74.

    PubMed  CAS  Google Scholar 

  • Gadian, D.G. 1996. NMR And Its Applications To Living Systems. London: Oxford University Press.

    Google Scholar 

  • Gillies, R.J., Scherer, P.G., Raghunand, N., Okerlund, L.S., Martinez-Zaguilan, R., Hesterberg, L. and Dale, B.E. 1991. Iteration of hybridoma growth and productivity in hollow fiber bioreactors using 31P NMR. Magn Reson Med. 18: 181–192.

    PubMed  CAS  Google Scholar 

  • Goodwin, D.W., Wadghiri, Y.Z. and Dunn, J.F. 1998. Micro-imaging of articular cartilage: T2, proton density, and the magic angle effect. Acad Radiol. 5: 790–798.

    Article  PubMed  CAS  Google Scholar 

  • Gorenflo, V.M., Smith, L., Dedinsky, B., Persson, B. and Piret, J.M. 2002. Scale-up and optimization of an acoustic filter for 200 L/day perfusion of a CHO cell culture. Biotechnol Bioeng. 80: 438–44.

    Article  PubMed  CAS  Google Scholar 

  • Gorter, A., van de Griend, R.J., van Eendenburg, J.D., Haasnoot, W.H. and Fleuren, G.J. 1993. Production of bi-specific monoclonal antibodies in a hollow-fibre bioreactor. J Immunol Methods. 161: 145–150.

    Article  PubMed  CAS  Google Scholar 

  • Gray, M.L., Burstein, D., Lesperance, L.M. and Gehrke, L. 1995. Magnetization transfer in cartilage and its constituent macromolecules. Magn Reson Med. 34: 319–325.

    PubMed  CAS  Google Scholar 

  • Gruetter, R., Novotny, E.J., Boulware, S.D., Rothman, D.L., Mason, G.F., Shulman, G.I., Shulman, R.G. and Tamborlane, W.V. 1992. Direct measurement of brain glucose concentrations in humans by 13C NMR spectroscopy. Proc Natl Acad Sci U S A. 89: 1109–1112.

    PubMed  CAS  Google Scholar 

  • Hammer, B.E., Heath, C.A., Mirer, S.D. and Belfort, G. 1990. Quantitative flow measurements in bioreactors by nuclear magnetic resonance imaging. Bio/Technology. 8: 327–330.

    Article  PubMed  CAS  Google Scholar 

  • Hardy, C.J., Saranathan, M., Zhu, Y. and Darrow, R.D. 2000. Coronary angiography by real-time MRI with adaptive averaging. Magn Reson Med. 44: 940–946.

    Article  PubMed  CAS  Google Scholar 

  • Hesse, S.J., Ruijter, G.J., Dijkema, C. and Visser, J. 2000. Measurement of intracellular (compartmental. pH by 31P NMR in Aspergillus niger. J Biotechnol. 77: 5–15.

    Article  PubMed  CAS  Google Scholar 

  • Hoult, D.I., Busby, S.J., Gadian, D.G., Radda, G.K., Richards, R.E. and Seeley, P.J. 1974. Observation of tissue metabolites using 31P nuclear magnetic resonance. Nature. 252: 285–287.

    Article  PubMed  CAS  Google Scholar 

  • Karantanas, A.H., Hadjigeorgiou, G.M., Paterakis, K., Sfiras, D. and Komnos, A. 2002. Contribution of MRI and MR angiography in early diagnosis of brain death. Eur Radiol. 12: 2710–2716.

    Article  PubMed  CAS  Google Scholar 

  • Kim, D.K., Ceckler, T.L., Hascall, V.C., Calabro, A. and Balaban, R.S. 1993. Analysis of water-macromolecule proton magnetization transfer in articular cartilage. Magn Reson Med. 29:, 211–215.

    PubMed  CAS  Google Scholar 

  • Kim, Y.J., Sah, R.L., Doong, J.Y. and Grodzinsky, A.J. 1988. Fluorometric assay of DNA in cartilage explants using Hoechst 33258. Anal Biochem. 174: 168–176.

    Article  PubMed  CAS  Google Scholar 

  • Ko, S.F., Wan, Y.L., Ng, S.H., Lee, T.Y., Cheng, Y.F., Wong, H.F. and Hsieh, M.J. 1999. MRI of thoracic vascular lesions with emphasis on two-dimensional time-of-flight MR angiography. Br J Radiol. 72: 613–620.

    PubMed  CAS  Google Scholar 

  • Koretsky, A.P. 2002. Functional assessment of tissues with magnetic resonance imaging. Ann N Y Acad Sci. 961: 203–205.

    PubMed  Google Scholar 

  • Koretsky, A.P. and Williams, D.S. 1992. Application of localized in vivo NMR to whole organ physiology in the animal. Ann Rev Physiol. 54: 799–826.

    Article  CAS  Google Scholar 

  • Lamminen, A. and Keto, P. 1996. MRI angiography. Duodecim. 112: 1533–1542.

    PubMed  CAS  Google Scholar 

  • Lehner, K.B., Rechl, H.P., Gmeinwieser, J.K., Heuck, A.F., Lukas, H.P. and Kohl, H.P. 1989. Structure, function, and degeneration of bovine hyaline cartilage: assessment with MR imaging in vitro. Radiology. 170: 495–499.

    PubMed  CAS  Google Scholar 

  • Lien, Y.H., Zhou, H.Z., Job, C., Barry, J.A. and Gillies, R.J. 1992. In vivo 31P NMR study of early cellular responses to hyperosmotic shock in cultured glioma cells. Biochimie. 74: 931–9.

    Article  PubMed  CAS  Google Scholar 

  • Macdonald, J.M., Grillo, M., Schmidlin, O., Tajiri, D.T. and James, T.L. 1998. NMR spectroscopy and MRI investigation of a potential bioartificial liver. NMR Biomed. 11: 55–66.

    Article  PubMed  CAS  Google Scholar 

  • Mancuso, A., Fernandez, E.J., Blanch, H.W. and Clark, D.S. 1990. A nuclear magnetic resonance technique for determining hybridoma cell concentration in hollow fiber bioreactors. Bio/Technology. 8: 1282–1285.

    Article  PubMed  CAS  Google Scholar 

  • Maroudas, A. 1968. Physicochemical properties of cartilage in the light of ion exchange theory. Biophys J. 8: 575–595.

    Article  PubMed  CAS  Google Scholar 

  • McAlindon, T.E., Watt, I., McCrae, F., Goddard, P. and Dieppe, P.A. 1991. Magnetic resonance imaging in osteoarthritis of the knee: correlation with radiographic and scintigraphic findings. Ann Rheum Dis. 50: 14–19.

    Article  PubMed  CAS  Google Scholar 

  • Melvin, B.K. and Shanks, J.V. 1996. Influence of aeration on cytoplasmic pH of yeast in an NMR airlift bioreactor. Biotechnol Prog. 12: 257–265.

    Article  PubMed  CAS  Google Scholar 

  • Mlynarik, V., Degrassi, A., Toffanin, R., Vittur, F., Cova, M. and Pozzi-Mucelli, R.S. 1996. Investigation of laminar appearance of articular cartilage by means of magnetic resonance microscopy. Magn Reson Imaging. 14: 435–442.

    Article  PubMed  CAS  Google Scholar 

  • Moon, R.B. and Richards, J.H. 1973. Determination of intracellular pH by 31P magnetic resonance. J Biol Chem. 248: 7276–7278.

    PubMed  CAS  Google Scholar 

  • Mow, V.C., Fithian, D.C. and Kelly, M.A. 1990. Fundamentals of articular cartilage and meniscus biomechanics. In: J. W. Ewing editor. Articular Cartilage and Knee Joint Function. New York: Raven Press Ltd. p 1–18.

    Google Scholar 

  • Neeman, M., Jarret, K.A., Sillerud, L.O. and Freyer, J.P. 1991. Self-diffusion of water in multicellular spheroids measured by magnetic resonance microimaging. Cancer Res. 51: 4072–4079.

    PubMed  CAS  Google Scholar 

  • Neves, A.A., Medcalf, N. and Brindle, K.M. 2003. Functional assessment of tissue engineered meniscal cartilage using magnetic resonance imaging and spectroscopy. Tissue Eng. 9: 49–57.

    Article  CAS  Google Scholar 

  • Papas, K.K., Long, R.C., Jr., Constantinidis, I. and Sambanis, A. 2000. Effects of short-term hypoxia on a transformed cell-based bioartificial pancreatic construct. Cell Transplant. 9: 415–422.

    PubMed  CAS  Google Scholar 

  • Pei, M., Solchaga, L.A., Seidel, J., Zeng, L., Vunjak-Novakovic, G., Caplan, A.I. and Freed, L.E. 2002. Bioreactors mediate the effectiveness of tissue engineering scaffolds. FASEB J. 16: 1691–1694.

    PubMed  CAS  Google Scholar 

  • Petersen, E.F., Fishbein, K.W., McFarland, E.W. and Spencer, R.G. 2000. 31P NMR spectroscopy of developing cartilage produced from chick chondrocytes in a hollow-fiber bioreactor. Magn Reson Med. 44: 367–372.

    Article  PubMed  CAS  Google Scholar 

  • Pfeuffer, J., Flogel, U. and Leibfritz, D. 1998. Monitoring of cell volume and water exchange time in perfused cells by diffusion-weighted 1H NMR spectroscopy. NMR Biomed. 11: 11–18.

    Article  PubMed  CAS  Google Scholar 

  • Poole, A.R. 1993. Cartilage in health and disease. In: McCarthy D.J. Arthritis and Allied Conditions: A Textbook of Rheumatology. Philadelphia: Lea & Febinger. p 279–333.

    Google Scholar 

  • Potter, K., Butler, J.J., Horton, W.E. and Spencer, R.G. 2000. Response of engineered cartilage tissue to biochemical agents as studied by proton magnetic resonance microscopy. Arthritis Rheum. 43: 1580–1590.

    Article  PubMed  CAS  Google Scholar 

  • Racher, A.J. and Griffiths, J.B. 1993. Investigation of parameters affecting a fixed bed bioreactor process for recombinant cell lines. Cytotechnology. 13: 125–131.

    Article  PubMed  CAS  Google Scholar 

  • Ratcliffe, A. and Niklason, L.E. 2002. Bioreactors and bioprocessing for tissue engineering. Ann N Y Acad Sci. 961: 210–215.

    Article  PubMed  CAS  Google Scholar 

  • Samuel, D. 2002. The bioartificial liver: hopes and realities. Gastroenterol Clin Biol. 26: 721–723.

    PubMed  Google Scholar 

  • Shu, S.Y., Wu, Y.M., Bao, X.M., Wen, Z.B., Huang, F.H., Li, S.X., Fu, Q.Z. and Ning, Q. 2002. A new area in the human brain associated with learning and memory: immunohistochemical and functional MRI analysis. Mol Psychiatry. 7: 1018–1022.

    Article  PubMed  CAS  Google Scholar 

  • Thelwall, P.E., Neves, A.A. and Brindle, K.M. 2001. Measurement of bioreactor perfusion using dynamic contrast agent-enhanced magnetic resonance imaging. Biotechnol Bioeng. 75: 682–690.

    Article  PubMed  CAS  Google Scholar 

  • Trattnig, S., Mlynarik, V., Breitenseher, M., Huber, M., Zembsch, A., Rand, T. and Imhof, H. 1999. MRI visualization of proteoglycan depletion in articular cartilage via intravenous administration of Gd-DTPA. Magn Reson Imaging. 17: 577–583.

    Article  PubMed  CAS  Google Scholar 

  • van de Kerkhove, M.P., Di Florio, E., Scuderi, V., Mancini, A., Belli, A., Bracco, A., Dauri, M., Tisone, G., Di Nicuolo, G., Amoroso, P., Spadari, A., Lombardi, G., Hoekstra, R., Calise, F. and Chamuleau, R.A. 2002. Phase I clinical trial with the AMC-bioartificial liver. Academic Medical Center. Int J Artif Organs. 25: 950–959.

    PubMed  Google Scholar 

  • van Zijl, P.C., Mooney, C.T., Faustino, P., Pekar, J., Kaplan, O. and Cohen, J.S. 1991. Complete separation of intracellular and extracellular information in NMR spectra of perfused cells by diffusion-weighted spectroscopy. Proc Nat Acad Sciences. 88: 3228–3232.

    Google Scholar 

  • Verheul, H.B., Balazs, R., Berkelbach van der Sprenkel, J.W., Tulleken, C.A., Nicolay, K., Tamminga, K.S. and van Lookeren Campagne, M. 1994. Comparison of diffusion-weighted MRI with changes in cell volume in a rat model of brain injury. NMR Biomed. 7: 96–100.

    PubMed  CAS  Google Scholar 

  • Wachsmuth, L., Juretschke, H.P. and Raiss, R.X. 1997. Can magnetization transfer magnetic resonance imaging follow proteoglycan depletion in articular cartilage? Magma. 5: 71–78.

    PubMed  CAS  Google Scholar 

  • Wang, M.D., Yang, M., Huzel, N. and Butler, M. 2002. Erythropoietin production from CHO cells grown by continuous culture in a fluidized-bed bioreactor. Biotechnol Bioeng. 77: 194–203.

    Article  PubMed  CAS  Google Scholar 

  • Wehrli, F.W., Shimakawa, A., Gullberg, G.T. and MacFall, J.R. 1986. Time-of-flight MR flow imaging: selective saturation recovery with gradient refocusing. Radiology. 160: 781–785.

    PubMed  CAS  Google Scholar 

  • Woessner, J.F. 1961. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Bioch Bioph. 93: 440–44.

    Article  CAS  Google Scholar 

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  1. Department of Biochemistry, University of Cambridge, Cambridge, UK

    A.A. Neves & K.M. Brindle

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  1. A.A. Neves
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  1. University of Bath, UK

    Julian Chaudhuri

  2. University College Dublin, Ireland

    Mohamed Al-Rubeai

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Neves, A., Brindle, K. (2005). Monitoring the Performance of Tissue Engineering Bioreactors Using Magnetic Resonance Imaging and Spectroscopy. In: Chaudhuri, J., Al-Rubeai, M. (eds) Bioreactors for Tissue Engineering. Springer, Dordrecht. https://doi.org/10.1007/1-4020-3741-4_15

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