In Vivo Noninvasive Monitoring of a Tissue Engineered Construct Using ¹H NMR Spectroscopy

Authors: Stabler, C. L.¹; Long Jr., R. C.²; Constantinidis, I.³; Sambanis, A.⁴

Source: Cell Transplantation, Volume 14, Numbers 2-3, 2005 , pp. 139-149(11)

Publisher: Cognizant Communication Corporation

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Abstract:

Direct, noninvasive monitoring of tissue engineered substitutes containing live, functional cells would provide valuable information on dynamic changes that occur postimplantation. Such changes include remodeling both within the construct and at the interface of the implant with the surrounding host tissue, and may result in changes in the number of viable cells in the construct. This study investigated the use of ¹H NMR spectroscopy in noninvasively monitoring the viable cell number within a tissue engineered construct in vivo. The construct consisted of mouse βTC3 insulinomas in a disk-shaped agarose gel, surrounded by a cell-free agarose gel layer. Localized ¹H NMR spectra were acquired from within implanted constructs, and the total choline resonance was measured. Critical issues that had to be addressed in accurately quantifying total choline from the implanted cells included avoiding signal from host tissue and correcting for interfering signal from diffusing solutes. In vivo NMR measurements were correlated with MTT assays and NMR measurements performed in vitro on explanted constructs. Total choline measurements accurately and noninvasively quantified viable βTC3 cell numbers in vivo, in the range of 1 × 10⁶ to more than 14 × 10⁶ cells, and monitored changes in viable cell number that occurred in the same construct over time. This is the first study using NMR techniques to monitor viable cell numbers in an implanted tissue substitute. It established architectural characteristics that a construct should have to be amenable to NMR monitoring, and it set the foundation for future in vivo investigations with other tissue engineered implants.

Keywords: 1H NMR spectroscopy; Total choline; βTC3 insulinoma cells; Pancreatic substitute; In vivo monitoring

Document Type: Review article

Affiliations: 1: Georgia Institute of Technology/Emory University Center for the Engineering of Living Tissues, 315 Ferst Drive, Atlanta, GA 30332-0363, Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, 313 Ferst Drive, Atlan 2: Georgia Institute of Technology/Emory University Center for the Engineering of Living Tissues, 315 Ferst Drive, Atlanta, GA 30332-0363, Fredrik Philips Magnetic Resonance Research Center, Department of Radiology, Emory University, 1639 Pierce Dri 3: Division of Endocrinology, Department of Medicine, University of Florida, PO Box 100226, Gainesville, FL 32610-0226, National High Magnetic Field Laboratory, 1800 E. Paul Dirac Dr., Tallahassee, FL 32310-3706 4: Georgia Institute of Technology/Emory University Center for the Engineering of Living Tissues, 315 Ferst Drive, Atlanta, GA 30332-0363, Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, 313 Ferst Drive, Atlan

Publication date: 2005-02-01

More about this publication?

Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.