Preclinical imaging methods for assessing the safety and efficacy of regenerative medicine therapies

Abstract

Regenerative medicine therapies hold enormous potential for a variety of currently incurable conditions with high unmet clinical need. Most progress in this field to date has been achieved with cell-based regenerative medicine therapies, with over a thousand clinical trials performed up to 2015. However, lack of adequate safety and efficacy data is currently limiting wider uptake of these therapies. To facilitate clinical translation, non-invasive in vivo imaging technologies that enable careful evaluation and characterisation of the administered cells and their effects on host tissues are critically required to evaluate their safety and efficacy in relevant preclinical models. This article reviews the most common imaging technologies available and how they can be applied to regenerative medicine research. We cover details of how each technology works, which cell labels are most appropriate for different applications, and the value of multi-modal imaging approaches to gain a comprehensive understanding of the responses to cell therapy in vivo.

Optical fluorescence imaging with shortwave infrared light emitter nanomaterials for in vivo cell tracking in regenerative medicine

“…After production, radiotracers are unstable, immediately lose their energy and generate some particles named as positrons. These particles interact with neighbouring electrons via annihilation process, and two produced photons (each having 511 keV energy) can be detected by PET scanners . Cell labelling PET radiotracers include 2‐[F‐18]‐fluoro‐2‐deoxy‐D‐glucose ( 18 F‐FDG) and [ 64 Cu]‐pyruvaldehyde‐bis (N4‐methylthiosemicarbazone) ( 64 Cu‐PTSM).…”

“…Cell labelling PET radiotracers include 2‐[F‐18]‐fluoro‐2‐deoxy‐D‐glucose ( 18 F‐FDG) and [ 64 Cu]‐pyruvaldehyde‐bis (N4‐methylthiosemicarbazone) ( 64 Cu‐PTSM). Single‐photon emission computed tomography (SPECT) imaging relies on detection of two low‐energy γ (gamma) photons being emitted from radioisotopes including 111 In‐oxine and technetium ( 99m Tc) exametazime ( 99m Tc‐hexamethyl propylene amine oxime [HMPAO]) …”

“…However, because HSV1‐tk has non‐human origin its structure induces the immune response in host tissue. In addition, blood‐brain barrier is the main obstacle for intracerebral use of this reporter gene in humans . In spite of some problems concerning to genetic manipulations of therapeutic cells, indirect labelling by reporter genes provides a better choice for cell fate tracing in comparison with direct method .…”

In vivo fate of free and encapsulated iron oxide nanoparticles after injection of labelled stem cells

“…This is a highly sensitive and robust method of monitoring the biodistribution of cells though it has a low spatial resolution (intra and inter organ monitoring of cells distribution is not possible). 15 . CC-BY-NC-ND 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

“…34 We and others have shown that most cells die after injection. 11,15,35 Therefore, understanding the in vivo fate of cell-labelling nanoparticles, especially following the death of the labelled cells is important for the interpretation of imaging studies and to assess the risk of toxicity. In the current study, we focus on the effect of formulation on the fate of SPIONs after the in vivo injection of labelled cells.…”