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Studies on imaging and tracking transplanted cells

Tampa, Fla. (Dec. 10, 2008) Successfully monitoring the distribution and fate of transplanted stem cells through imaging and subsequent tracking would aid clinicians in their ability to evaluate the efficacy of transplanted cells. Three studies published in the current issue of Cell Transplantation (Vol. 17, No.8) assess various imaging techniques and evaluate the degree to which the techniques afford clinicians useable imaging and tracking data.

Bioluminescent imaging of human fetal hepatocytes

In a study conducted by Dr. Mark A. Zern and colleagues at the Transplant Research Institute, University of California Davis Medical Center, the use of bioluminescent imaging to track transplanted immortalized human fetal hepatocytes injected into mice was evaluated. According to the researchers, it was essential for them to evaluate via noninvasive monitoring the effectiveness of transplanted cells to engraft and repopulate the recipient liver. Using double or triple fusion lentiviral vectors in a mouse model transplanted with immortalized fetal hepatocytes, the researchers for the first time imaged in vivo human hepatic progenitor cells transplanted into a rodent model.

"Our results, confirmed by a series of biochemical and histologic modalities, indicate that this imaging system appears to be a promising approach for repeatedly and noninvasively monitoring transplanted hepatic cells," said Zern.

Contact: Dr. Mark A. Zern, Transplant Institute, UC Davis Medical Center, (916) 734-8063;

Using small particles of iron oxide

A second study involving imaging published in this issue of Cell Transplantation (Vol. 17 No. 8), evaluated the use of cloned mensenchymal stem cells (MSC) labeled with clinically-approved small particles of iron oxide (SPIO) for the treatment of experimental autoimmune encephalomyelitis (EAE). Results revealed an increase in disease severity when using SPIO while a control experiment with unlabeled MSC did not affect disease severity.

"Treatment with SPIO alone did not alter disease course," said study lead author Dr. Richard Schafer of the Institute of Clinical and Experimental Transfusion Medicine at University Hospital, Tubingen, Germany. "Iron deposition was present in the group treated with SPIO-labeled MSC, indicating that in vivo the initially cell surface bound iron detached from the MSC. Our results could be of great importance for imaging patients in the clinical setting, indicating that in vivo application of SPIO-labeled MSC needs to be performed with caution since the cell-derived exposure of iron can lead to disease aggravation."

Contact: Dr. Richard Schafer, University Hospital, Tubingen, Germany + 49-7071-295240

Three different labeling methods evaluated

In a study conducted at the Center for Research in Cardiovascular Medicine at the State University of New York (SUNY) Buffalo, researchers experimented with three different labeling methods for tracking transplanted mensenchymal stem cells (MSCs): adenovirus-mediated expression of enhanced green fluorescence protein (EGFP); B-galactosidase (LacZ); and live cell DAPI nuclear staining. Each was used to label porcine bone marrow-derived MSCs in cultures.

"Although MSCs could be efficiently labeled by these methods in cultures, whether the labels could be reliably detected after in vivo implantation, particularly in a large animal model, needed to be examined," said study lead author Dr. Techung Lee of the SUNY Buffalo Department of Biochemistry.

The research team experienced 'inconsistency' when attempting to track EGFP and LacZ-labeled MSCs while the DAPI-labeled cells could be 'stably retained' in the implanted MSCs for at least one month after implantation.

"These labeled MSCs could be detected histologically with little ambiguity," commented Lee.

The researchers concluded that DAPI labeling could be reliably used for MSC tracking in both small and large animal models because the brightly emitted blue fluorescence is exclusively confined to the nucleus, generating a sharper image that was advantageous for stem cell identification.

Contact: Dr. Techung Lee, SUNY Buffalo (716) 829-3106

"The availability of in vivo monitoring of transplanted cells allows visualization of cell migration and proliferation, adding a critical parameter for safety and efficacy measure," said Cesar Borlongan, Ph.D. at the University of South Florida Health, and associate editor of Cell Transplantation.


Contact: Dr. Mark A. Zern
Cell Transplantation Center of Excellence for Aging and Brain Repair

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