Institute of Functional Interfaces

Organotypic tissue models in MRI method development

  • chair:

    Gottwald, E. / Giselbrecht, S. (2014) 

  • place:

    Z Med Phys, 2014, 24, (2), 89-90 doi: 10.1016/j.zemedi.2014.02.006 

  • Date: Mai 2014

Abstract

MRI method development usually relies on the use of MRI phantoms, animals or cadavers. Whereas the former is a valuable tool to optimize the performance of the imaging device without putting a living subject to risk, MRI techniques capable to monitor physiological processes have to be established in living matter, be it a part of, or the whole animal or human itself. But since especially MRI method development may impose severe risks on the subject studied, in vitro models that mimic in vivo physiology and tissue architecture would be a helpful tool. At the same time, these systems would be able to be controlled precisely with regard to e.g. (blood) flow rate, flow modality, oxygen tension, and cell number to mimic not only normal physiologic conditions but furthermore also conditions in specific disease states, such as ischemia, for instance. In addition, the use of human cells in such bioreactors might deliver more physiologically relevant data compared to animal testing, which by nature, is done in the wrong species. Although some MRI-compatible bioreactors have already been developed [1–5], usually these bioreactors do focus on specialized aspects of the respective tissue under consideration and for which purpose they work exquisitely well.

In vitro systems with a more generalized spectrum of applications would considerably add to MRI method development since bioreactor development and manufacturing may not be easily transferred into a clinical setting particularly with regard to the handling properties of the respective system. To overcome these difficulties, besides MRI-compatibility, bioreactors with a self-explaining handling, a closed circulation loop for medium supply with minimal contamination risk and a modular setup are needed. Finally, the cell-containing structures should ensure not only the maintenance but also the growth, self-organization and/or the possibility for tissue engineering of the tissue inoculated. First attempts to achieve this have been made by Weibezahn et al. [6] who invented a chip system with microcavity arrays for the three-dimensional cultivation of cells. Meanwhile, three-dimensionality is widely accepted as being one of the key characteristics of organotypic tissue cultures and citing all the relevant literature is beyond the scope of this forum. With the chip as the key component, bioreactors for active nutrient and gas supply were constructed that showed optimal support for primary liver cell functions over a period of 14 days [7]. In the following years a number of cell lines, but also primary cells, especially stem cells, have been cultivated in the system and again it could be demonstrated that this bioreactor type is suitable for stem cell maintenance, stem cell differentiation and the induction of organotypic behaviour even in cancer cell lines [8–11]. Moreover, the system displayed a homogeneous flow distribution over the cell-containing microcavity array area and residue-free wash-out characteristics as shown by the use of Gd-DOTA imaged in an experimental animal MRI at 9.4 T field strength [12] which might be a useful system when the metabolism and the washout of traceable active pharmaceutic ingredients (API) or drug candidates is of interest.

In conjunction with other MRI/NMR-modalities and additional analytical techniques MRI-compatible bioreactors will most likely play an increasing role in MRI-method development that might shorten the time to develop new therapeutic treatment modalities and might even deliver insights into healthy and diseased tissues with an unprecedented resolution, e.g. by the use of cryo-coils, X-nuclei, and information content that is clearly more desirable than existing minimally invasive methods such as biopsies [13].

 

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