title: Imaging technologies for monitoring the safety, efficacy and mechanisms of action of cell-based regenerative medicine therapies in models of kidney disease.
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.
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK; Centre for Preclinical Imaging, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Sharkey
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK; Centre for Preclinical Imaging, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Lauren
authors.initials: L
authors.lastname: Scarfe
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Santeramo
authors.affiliation: Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Garcia-Finana
authors.affiliation: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Park
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK; Centre for Preclinical Imaging, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Harish
authors.initials: H
authors.lastname: Poptani
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK; Centre for Preclinical Imaging, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Bettina
authors.initials: B
authors.lastname: Wilm
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK; Centre for Preclinical Imaging, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Arthur
authors.initials: A
authors.lastname: Taylor
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK; Centre for Preclinical Imaging, University of Liverpool, Liverpool L69 3GE, UK. Electronic address: p.a.murray@liv.ac.uk.
authors.forename: Patricia
authors.initials: P
authors.lastname: Murray
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy / Q000009:adverse effects* / Q000379:methods*; D006801:Humans; D007668:Kidney / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D057054:Molecular Imaging / Q000379:methods*; D044968:Regenerative Medicine / Q000379:methods*; D012449:Safety
keywords: Biodistribution; Cell tracking; Kidney function; Multispectral optoacoustic tomography; Preclinical imaging; Stem cells