Tracking Stem Cell Therapy in the Myocardium: Applications of Positron Emission Tomography

Abstract

The introduction of stem cells and/or progenitor cells into damaged myocardium has promising therapeutic potential in ischemic heart diseases and dilated cardiomyopathy. However, understanding the biologic mechanisms and the outcomes of transplanted cells during cardiac regenerative therapy remains mostly limited to histological assessment. Positron emission tomography (PET) is a sensitive molecular imaging modality that can non-invasively assess stem cell retention, survival, and function after transplantation. Two radiolabel approaches have been explored to implement PET: 1) direct cell labeling with a radionuclide; and 2) reporter gene-based cell labeling. Direct cell labeling has previously been used for early tracking of transplanted stem cells into the myocardium in several therapeutic clinical trials. Stem cells can also be labeled after transfection with a reporter gene, which can subsequently be visualized by using a PET reporter probe that binds to the reporter gene, therefore allowing serial in vivo evaluation of cell viability and proliferation in long-term follow-up studies. Recently, some studies successfully used this method to visualize implanted stem cells by PET imaging in animals. With the projected rapid growth of cell therapy for heart disease, PET is expected to play a major role in monitoring relevant changes that occur at every stage in cardiac regenerative therapy. These two cell tracking approaches used for PET imaging are reviewed here and compared against other imaging modalities.

PET Demonstrates Functional Recovery After Transplantation of Induced Pluripotent Stem Cells in a Rat Model of Cerebral Ischemic Injury

“…PET is one of the best-suited modalities to evaluate stem cell therapy, since it can be used in patients clinically for both cell trafficking and monitoring the response to therapy (16,17). PET with 18 F-FDG, a powerful tool with which to study the etiopathogenesis and progression of neurologic diseases, has recently been applied to detect the subtle changes of glucose metabolism in vivo after stem cell therapy in various neurologic disease models, including traumatic brain injury (18), Parkinson disease (19)(20)(21), and Huntington disease (22).…”

In Vivo Cell Tracking with Bioluminescence Imaging

“…Tracking of transplanted cells via imaging tools by visualizing the fate, function, migration, and homing of the cells using in vivo models would be highly valuable for research on cell-based therapies [1,2]. Implanted cells can be visualized using anatomical imaging modalities, such as magnetic resonance imaging and computed tomography, which have excellent anatomical resolution and no depth limitation [3][4][5][6]; however, these techniques have limitations of low sensitivity, low throughput, and high cost of instrumentation. Due to the highest sensitivity and low cost, optical imaging has been used most commonly for in vivo cell tracking [7,8].…”

Adenovirus-mediated expression of human sodium-iodide symporter gene permits in vivo tracking of adipose tissue-derived stem cells in a canine myocardial infarction model

“…There are several in vivo stem cell tracking methods based on coupling different cell labeling techniques and imaging modalities to track the engraftment and survival of transplanted stem cells in diseased hearts [11,12]. The reporter gene system is believed to provide information about the distribution, homing, survival, and functionality of transplanted stem cells for a relatively prolonged duration, and more effectively than direct cell-radiolabeling methods [11][12][13].…”