Emerging roles for integrated imaging modalities in cardiovascular cell-based therapeutics: a clinical perspective

Abstract

Despite preclinical promise, the progress of cell-based therapy to clinical cardiovascular practice has been slowed by several challenges and uncertainties that have been highlighted by the conflicting results of human trials. Most telling has been the revelation that current strategies fall short of achieving sufficient retention and engraftment of cells to meet the ambitious objective of myocardial regeneration. This has sparked novel research into the refinement of cell biology and delivery to overcome these shortcomings. Within this context, molecular imaging has emerged as a valuable tool for providing noninvasive surveillance of cell fate in vivo. Direct and indirect labelling of cells can be coupled with clinically relevant imaging modalities, such as radionuclide single photon emission computed tomography and positron emission tomography, and magnetic resonance imaging, to assess their short- and long-term distributions, along with their viability, proliferation and functional interaction with the host myocardium. This review details the strengths and limitations of the different cell labelling and imaging techniques and their potential application to the clinical realm. We also consider the broader, multifaceted utility of imaging throughout the cell therapy process, providing a discussion of its considerable value during cell delivery and its importance during the evaluation of cardiac outcomes in clinical studies.

Renin Inhibition Improves the Survival of Mesenchymal Stromal Cells in a Mouse Model of Myocardial Infarction

“…For that purpose, BLI has been shown to strongly correlate with the number of cells both in vitro [7] and in vivo [23]. Thus, optical bioluminescence imaging has been adopted in many preclinical studies to longitudinally monitor cell fate, especially in animal models of CHD [13, 24, 20, 23, 25]. Our study confirmed prior observations [5] with poor stem cell survival 24–48 h following delivery into the infarcted heart.…”

Stem Cells for the Therapy of Ischemic Heart Disease: Advances and Prospects

“…К сожале нию, несмотря на некоторые различия в эф фективности этих методов доставки клеток, в настоящее время сохранение МСК и их при живление в миокарде остается недостаточно совершенным во всех случаях [143].…”

Noninvasive Assessment of Cell Fate and Biology in Transplanted Mesenchymal Stem Cells

“…While direct labelling is used to monitor cell fate only shortly after transplantation, mainly due to the progressive dilution of the signal - as a consequence of cell division - and cell toxicity issues - which may vary depending on the agent and doses used, reporter gene imaging allows long-term assessment of cell fate with longitudinal and repetitive imaging[26,27]. Using this strategy, cells are engineered to over-express or produce de novo an enzyme, receptor or protein: when this protein interacts with an exogenously administered substrate, it results in a signal that can be used to distinguish not only implanted cells from endogenous cells with high specificity, but also modulations in intracellular functions[28].…”

“…Due to the lack of spatial resolution and tissue depth penetration, the use of BLI is restricted to small animal studies (rats and mice)[26]. However, this strategy can be adapted to clinically used imaging modalities, such as Positron Emission Tomography (PET) or Single-Photon Emission Computed Tomography (SPECT), using - for instance - thymidine kinase (TK) or human sodium-iodide symporter (hNIS) as reporter genes, respectively[19,27]. Therefore, BLI may be considered as a starting step in the development of novel imaging strategies in high-throughput preclinical studies.…”