A study conducted by a team of researchers from Spain and Belgium indicated that, different stem cell populations displayed changes when tested with three different labeling agents. These changes were recorded in the stem cells phenotype, migration abilities and biological behavior and were determined on the kind of contrast agent utilized.

The study published in the November issue of Cell Transplanti, contained the findings of the Belgian and Spanish researchers.

The tests were conducted on USPIO (ultra small superparamagnetic iron oxide) with Endorem, Resovist and Sinerem as contrast agents on rat multipotent adult progenitor cells (rMAPC), mouse mensenchymal stem cells (mMSC) and mouse embryonic stem cells (mESC).

The findings indicated that comparison of different cell populations revealed varied results with the labeling on each of the (U)SPIOs.

"This means that labeling methods will likely need to be optimized for every cell type," said Dr. Crabbe. "Over time we saw a dilution of (U)SPIOs and a decrease of iron in the cells."

While noninvasive imaging determines post-transplantation in stem cell research, the study has not scientifically substantiated the impact of the use of contrast agents on transplanted stem cells in vivo by MRI.

Researchers discovered that (U)SPIO labeling has "no significant alterations" in cell phenotypes and that the label "does not significantly alter stem cell differentiation."

"Sinerem decreased proliferation of mMSC while both Sinerem and Endorem affected the proliferation rate of rMAPC, although prolonged culture, until seven days, resulted in restoration of the proliferation rate," noted Dr. Crabbe. "We also found that higher concentrations of Sinerem and Endorem were needed for cell labeling to achieve similar MRI detectability."

The conclusive findings of the research suggested that analysis of the labeling efficiency of each cell for every new contrast agent combination was to be followed in vivo by MRI. The finding also aimed at evaluating the biological behavior of each cell. Currently the study was restricted to examine the labeling effects on proliferation and not on differentiation.

"Although labeling of stem cells with MRI is promising, there are some limitations," concluded Dr. Crabbe. "More optimal particles are needed that can be taken up without the need of potentially toxic agents. Also, there is the problem of particle dilution over time as cells divide. When grafted cells continue to proliferate, loss of signal occurs."

There has been a knowledge gap between survival and distribution of the stem cell populations used in the therapy, said Dr. Julio Voltarelli, professor of clinical medicine and clinical immunology at the University of Sao Pãulo, Brazil and section editor for Cell Transplantation.

"Many studies have tried to close this gap by using radioactive or nonradioactive labeling of the cells in order to follow their fate in the organism," said Dr. Voltarelli. "However, this paper demonstrates that such labeling may alter stem cell behavior, such as proliferative potential, and give biased information when compared to no labeled cells."