Imaging technologies for monitoring the safety, efficacy and mechanisms of action of cell-based regenerative medicine therapies in models of kidney disease

Authors: Jack Sharkey, Lauren Scarfe, Ilaria Santeramo, Marta Garcia-Finana, Brian K. Park, Harish Poptani, Bettina Wilm, Arthur Taylor, Patricia Murray

Abstract:

The incidence of end stage kidney disease is rising annually and it is now a global public health problem. Current treatment options are dialysis or renal transplantation, which apart from their significant drawbacks in terms of increased morbidity and mortality, are placing an increasing economic burden on society. Cell-based Regenerative Medicine Therapies (RMTs) have shown great promise in rodent models of kidney disease, but clinical translation is hampered due to the lack of adequate safety and efficacy data. Furthermore, the mechanisms whereby the cell-based RMTs ameliorate injury are ill-defined. For instance, it is not always clear if the cells directly replace damaged renal tissue, or whether paracrine effects are more important. Knowledge of the mechanisms responsible for the beneficial effects of cell therapies is crucial because it could lead to the development of safer and more effective RMTs in the future. To address these questions, novel in vivo imaging strategies are needed to monitor the biodistribution of cell-based RMTs and evaluate their beneficial effects on host tissues and organs, as well as any potential adverse effects. In this review we will discuss how state-of-the-art imaging modalities, including bioluminescence, magnetic resonance, nuclear imaging, ultrasound and an emerging imaging technology called multispectral optoacoustic tomography, can be used in combination with various imaging probes to track the fate and biodistribution of cell-based RMTs in rodent models of kidney disease, and evaluate their effect on renal function.

Keywords

Stem cells; Preclinical imaging; Multispectral optoacoustic tomography; Cell tracking; Biodistribution; Kidney function

Citation: Jack Sharkey, Lauren Scarfe, Ilaria Santeramo, Marta Garcia-Finana, Brian K. Park, Harish Poptani, Bettina Wilm, Arthur Taylor, Patricia Murray Imaging technologies for monitoring the safety, efficacy and mechanisms of action of cell-based regenerative medicine therapies in models of kidney disease http://dx.doi.org/10.1016/j.ejphar.2016.06.056

Received: 7 May 2016, Accepted: 30 June 2016, Available online: 1 July 2016

Copyright: © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).

Concluding remarks

The development and application of in vivo imaging strategies to accurately assess the safety, efficacy and mechanisms of action of cell-based RMTs will lead to a better understanding of their potential hazards and therapeutic benefits, thus underpinning the safe introduction of these new therapies into the clinic. Indeed, in vivo imaging approaches are already providing novel insights into the mechanisms of action of RMTs in rodent models of kidney disease, which is likely to lead to safer and more effective therapies in the future. For instance, we now know that for the majority of therapeutic cell-types, the regenerative effects on host renal tissue are mediated by paracrine or endocrine factors. Therefore, if these factors could be defined, it could be possible to administer them instead of the cells, thus bypassing some of the potential hazards associated with cell administration. Although the focus of this review has been on renal cell-based RMTs, it is worth noting that in rodent models of various other diseases, including heart disease (Malliaras and Marban, 2011) and spinal cord injury (De Paul et al., 2015), there is increasing evidence that the therapeutic effects are mediated by paracrine factors rather than by the cells themselves.

Acknowledgements

PM thanks Prof Norbert Gretz, University of Heidelberg, for insightful comments regarding the recruitment of intrapulmonary arteriovenous anastomoses. The authors acknowledge funding from the UK Regenerative Medicine Platform Safety and Efficacy Hub (grant MR/K026739/1), Alder Hey Children's Kidney Fund, the EU FP7 Initial Training Network, ‘NephroTools’ and the EU FP7 project ‘StemTrack’. In vivo imaging data in this article were obtained in the Centre for Preclinical Imaging (CPI) of the University of Liverpool. The CPI has been funded by the UK Medical Research Council (grant MR/L012707/1).

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