Vol 19, N 8, 2010


The Regenerative Medicine Journal

Do MRI contrast agents change stem cell phenotypes?

Tampa, Fla. (Nov. 03, 2010)—Noninvasive imaging plays an important posttransplantation role in stem cell research, but questions regarding whether the contrast agents used to track transplanted stem cells in vivo via MRI have an impact on the cells have largely gone unanswered. Accordingly, researchers tested three different labeling agents on three different stem cell populations to determine what effect, if any, the labeling agents had on stem cell phenotype, biological behavior, and migration abilities.

The team of researchers from Belgium and Spain tested USPIO (ultra small superparamagnetic iron oxide) contrast agents Resovist®, Endorem®, and Sinerem® on mouse embryonic stem cells (mESC), rat multipotent adult progenitor cells (rMAPC), and mouse mensenchymal stem cells (mMSC). Their study is published in the current issue of Cell Transplantation (19:8), now freely available on-line at http://www.ingentaconnect.com/content/cog/ct/

“Due to their physiochemical characteristics, label uptake and particle stability in cells differs between different types of labeling agents,” said corresponding author Dr. Annelies Crabbe.  “Also, some reports have suggested that (U)SPIO labeling may affect the biological properties of cells, but there is limited data comparing labeling efficiency and potential toxic effects that labeling agents may have on the biology and behavior of different stem/progenitor cell populations.”

The researchers found the labeling efficiency with each of the (U)SPIOs 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 Dr. Crabbe. “Over time we saw a dilution of (U)SPIOs and a decrease of iron in the cells.”

On the issue of whether (U)SPIO labeling has a biological effect on cells, the researchers discovered “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 7 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 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. They noted that their 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,” 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.”

“Survival and distribution of stem cell populations used for in vivo therapy is a big hole in the present knowledge of these therapies. Many studies tried to close this hole using radioactive or nonradioactive labeling of the cells in order to follow their fate in the organism” commented Prof. Julio Voltarelli, Professor of Clinical Medicine & Clinical Immunology at the University of Sao Pãulo, Brazil and section editor for Cell Transplantation.

“However, this paper demonstrates that such labeling may alter stem cell behavior, such as proliferative potential, and give biased information compared to nonlabeled cells.”

Contact: Dr. Annelies Crabbe, Stem Cell Institute. K.U. Leuven, O&N1- Herestraat 49, bus 804, 3000 Leuven, Belgium. Tel: 003216330292;  Fax: 003216330294; E-mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it

The editorial offices for CELL TRANSPLANTATION are at the Center of Excellence for Aging and Brain Repair, College of Medicine, the University of South Florida and the Diabetes Research Institute, University of Miami Miller School of Medicine. Contact, David Eve, Ph.D., at This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Camillo Ricordi, M.D., at This e-mail address is being protected from spambots. You need JavaScript enabled to view it

News release by Florida Science Communications, www.sciencescribe.net

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