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Clinical imaging in regenerative medicine

Abstract

In regenerative medicine, clinical imaging is indispensable for characterizing damaged tissue and for measuring the safety and efficacy of therapy. However, the ability to track the fate and function of transplanted cells with current technologies is limited. Exogenous contrast labels such as nanoparticles give a strong signal in the short term but are unreliable long term. Genetically encoded labels are good both short- and long-term in animals, but in the human setting they raise regulatory issues related to the safety of genomic integration and potential immunogenicity of reporter proteins. Imaging studies in brain, heart and islets share a common set of challenges, including developing novel labeling approaches to improve detection thresholds and early delineation of toxicity and function. Key areas for future research include addressing safety concerns associated with genetic labels and developing methods to follow cell survival, differentiation and integration with host tissue. Imaging may bridge the gap between cell therapies and health outcomes by elucidating mechanisms of action through longitudinal monitoring.

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Figure 1: The human body contains 3.7 × 1013 cells10.

Katie Vicari/Nature Publishing Group

Figure 2: Tracking cell fate by noninvasive imaging requires either direct or indirect labeling.

Katie Vicari/Nature Publishing Group

Figure 3: Examples of clinical imaging used to identify and track labeled cells in the body.

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Acknowledgements

The authors would like to acknowledge Kristine Evers for proofreading of the manuscript and the following grant support: M.M. was supported by the Commonwealth of Pennsylvania, Department of Health (4100061184), NINDS (R01NS082226) and NIBIB (1R01EB016629). C.E.M. was supported by US National Institutes of Health (NIH) grants P01HL094374, R01HL084642, U01HL100405 and P01GM81619. J.A.F. was supported in part by the intramural research program in the Clinical Center and National Institutes of Biomedical Imaging and Bioengineering at the US National Institutes of Health. A.M. was supported in part by NIH grant R24 DK096465.

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Correspondence to Charles E Murry or Joseph A Frank.

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C.E.M. is a scientific founder and equity holder in BEAT Biotherapeutics.

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Naumova, A., Modo, M., Moore, A. et al. Clinical imaging in regenerative medicine. Nat Biotechnol 32, 804–818 (2014). https://doi.org/10.1038/nbt.2993

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