Study: MRI contrast agents can change stem cell proliferation

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Changes in stem cell proliferation depend on the type of contrast agent used and will require assessment of the optimal USPIO (ultrasmall superparamagnetic iron oxide) for each individual stem cell population to ensure the most sensitive detection without associated toxicity, according to a study published in this month’s issue of Cell Transplantation.

Experimental stroke models have been developed to determine potential beneficial effects of stem/progenitor cell-based therapies. MRI offers a high-resolution, clinically relevant method allowing in vivo monitoring of cells labeled with contrast agents. In this study, a team of researchers from Belgium and Spain tested USPIO contrast agents Resovist, Endorem and Sinerem on mouse embryonic stem cells, rat multipotent adult progenitor cells and mouse mensenchymal stem cells.

The researchers found the labeling efficiency with each of the USPIOs varied significantly when different stem cell populations were compared. "This means that labeling methods will likely need to be optimized for every cell type," said Annelies Crabbe, PhD, from Stem Cell Institute, KU Leuven in Belgium.

Labeling with USPIOs in the range that allowed detection of cells by in vivo MRI did not affect differentiation of stem cells when labeled with concentrations of particles needed for MRI-based visualization, according to Crabbe and colleagues.

"Sinerem decreased proliferation of mouse mesenchymal stem cells while both Sinerem and Endorem affected the proliferation rate of rat multipotent adult progenitor cells, although prolonged culture, until seven days, resulted in restoration of the proliferation rate," noted Crabbe. "We also found that higher concentrations of Sinerem and Endorem were needed for cell labeling to achieve similar MRI detectability."

The researchers concluded that it will be necessary to evaluate the efficiency of cell labeling for every new contrast agent combination aimed at being followed in vivo by MRI. Also, the effect on biological behavior of cells should be examined. The researchers noted that the results were limited to examining the effects of labeling on proliferation, not differentiation.

"Although labeling of stem cells with MRI is promising, there are some limitations," said 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."

Crabbe and colleagues concluded that successful use of USPIOs for MRI-based visualization will require assessment of the optimal USPIO for each individual stem cell population to ensure the most sensitive detection without associated toxicity.

According to Julio Voltarelli, MD, PhD, professor of clinical medicine and clinical immunology at the University of São Paulo, Brazil and section editor for Cell Transplantation, there has been a knowledge gap regarding the survival and distribution of stem cell populations used for in vivo therapy. "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 Voltarelli. "However, this paper demonstrates that such labeling may alter stem cell behavior, such as proliferative potential, and give biased information when compared to non labeled cells."