Using positron emission tomography (PET) imaging with bioluminescence—the light produced by a chemical reaction within an organism—researchers are starting to understand the behavior of transplanted or implanted stem cells that may one day be used to develop new treatments for disease.
According to a study in the December Journal of Nuclear Medicine, scientists have found that using the unique combination of noninvasive PET imaging and optical (bioluminescent) imaging is "an ideal method for tracking stem cell transplantation in small animal models," said Zhenghong Lee, an associate professor of nuclear medicine/radiology and biomedical engineering departments at Case Western Reserve University in Cleveland, Ohio. Researchers were able to use these two imaging techniques to "follow" stem cells for a longer time than previously had been achieved to determine their "fate," explained Lee.
Human mesenchymal stems cells or multipotent marrow stromal cells (hMSCs) are self-renewing adult stem cells that are found in adult donor bone marrow. These stem cells, the body’s blank or "master" cells, may differentiate (or change) into bone, fat tissue and cartilage, said Lee. "The promise of MSC therapies—derived from adult bone marrow and used as a viable and renewable source of stem cells—mandates research leading to a better understanding of the long-term fate and trafficking of transplanted MSCs in animal and human subjects," said the investigator at Case Western’s Center for Stem Cell and Regenerative Medicine. These progenitor cells may have great potential in providing future treatments for heart diseases, brain disorders and cancer and greatly reduce the need to use embryonic stem cells or other fetal tissues.
Specifically, this imaging research could help optimize treatments for individuals with graft-versus-host disease, a life-threatening condition where immune cells from donated marrow or cord blood attack the body of a bone marrow transplant patient, said Lee. Additionally, bone marrow stem cells may help regenerate cells in individuals with heart disease (heart attacks) or brain disorders (strokes, multiple sclerosis) or bone fractures. They could act as a drug delivery vehicle for cancer patients, he added. Much research in these areas still needs to be done "since there are many things that we don’t know about stem cell biology," noted Lee.
For this study, researchers used a fusion protein combining firefly luciferase (a light-emitting substance) for optical imaging, a red fluorescent protein for cell separation and a virus enzyme thymidine kinase for PET imaging in mice to visualize biological processes at the molecular level. "The triple-fusion reporter approach resulted in a reliable method of labeling stem cells for investigation by use of both small-animal PET imaging and bioluminescent imaging," said Lee. PET is a powerful molecular imaging procedure that noninvasively demonstrates the function of genes, cells and organs/tissues, providing information about the biochemistry processes, metabolic activities and body functions.
PET scans use very small amounts of radioactive pharmaceuticals that are detected or "traced" by a special type of camera that works with computers to provide quantitative pictures of the area of the body being imaged. To image dim light from bioluminescence—the process of light emission in living organisms—researchers use an ultra-sensitive camera from an external vantage point. This research is detailed in "Imaging of Mesenchymal Stem Cell Transplant by Bioluminescence and PET."
In a related Journal of Nuclear Medicine article, the growing number of exciting animal and preclinical studies are explored, revealing the "immense potential in stem cell-based therapies, particularly in the area of treating cardiovascular diseases," said Joseph C. Wu, assistant professor of cardiovascular medicine and radiology at Stanford University School of Medicine in Stanford, Calif. Wu and co-author Sarah J. Zhang review the basic principles of current techniques for cardiac stem cell tracking, compare the relative advantages and disadvantages of these imaging modalities and discuss the future prospect of cardiac stem cell trafficking. "Comparison of Imaging Techniques for Tracking Cardiac Stem Cell Therapy" is the first article in the journal’s new monthly feature called "Focus on Molecular Imaging."
"The unique information obtained from molecular imaging techniques is particularly helpful in evaluating cell engraftment and may shed light on the mixed findings regarding stem cell–based therapy," said Wu. "The current noninvasive imaging approaches for tracking stem cells in vivo include imaging with magnetic particles, radionuclides, quantum dots, reporter genes, and fluorescence and bioluminescence imaging," he added. "It is possible that a tailored combination of two or more techniques may provide the most ideal information profile for clinical applications," concluded Wu.
Additional co-authors of "Imaging of Mesenchymal Stem Cell Transplant by Bioluminescence and PET" include Zachary Love, nuclear medicine/radiology department; Fangjing Wang and Nicholas Salem, biomedical engineering department; Amad Awadallah, orthopedics department, James Dennis, orthopedics department and Center for Stem Cell and Regenerative Medicine, and Yuan Lin, hematology/oncology department, all at Case Western Reserve University in Cleveland, Ohio; and Andrew Weisenberger and Stan Majewski, Thomas Jefferson National Accelerator Facility, Newport News, Va.
"Comparison of Imaging Techniques for Tracking Cardiac Stem Cell Therapy" was co-written by Wu and Sarah J. Zhang, Stanford University School of Medicine, Stanford, Calif.
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