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Tracking the fate of stem cell implants with fluorine-19 MRI.

Gaudet JM, Ribot EJ, Chen Y, Gilbert KM, Foster PJ - PLoS ONE (2015)

Bottom Line: The 19F signal decreased over time in both models, with a more rapid decrease in the syngeneic model.In the xenograft model, all mice had detectable signal at endpoint.However, in certain circumstances the transfer of cellular label to other bystander cells may confuse interpretation of the long-term fate of the transplanted cells.

View Article: PubMed Central - PubMed

Affiliation: Imaging Research Laboratories, Robarts Research Institute, London, ON, Canada; Department of Medical Biophysics, University of Western Ontario, London, ON, Canada.

ABSTRACT

Background: In this study we used cellular magnetic resonance imaging (MRI) to detect mesenchymal stem cells (MSC) labeled with a Fluorine-19 (19F) agent. 19F-MRI offers unambiguous detection and in vivo quantification of labeled cells.

Methods: We investigated two common stem cell transplant mouse models: an immune competent, syngeneic transplant model and an immune compromised, xenograft transplant model. 19F labelled stem cells were implanted intramuscularly into the hindlimb of healthy mice. The transplant was then monitored for up to 17 days using 19F-MRI, after which the tissue was excised for fluorescence microscopy and immunohistochemisty.

Results: Immediately following transplantation, 19F-MRI quantification correlated very well with the expected cell number in both models. The 19F signal decreased over time in both models, with a more rapid decrease in the syngeneic model. By endpoint, only 2/7 syngeneic mice had any detectable 19F signal. In the xenograft model, all mice had detectable signal at endpoint. Fluorescence microscopy and immunohistochemistry were used to show that the 19F signal was related to the presence of bystander labeled macrophages, and not original MSC.

Conclusions: Our results show that 19F-MRI is an excellent tool for verifying the delivery of therapeutic cells early after transplantation. However, in certain circumstances the transfer of cellular label to other bystander cells may confuse interpretation of the long-term fate of the transplanted cells.

Show MeSH
In vitro validation of 19F-MRI quantification accuracy.Quantification was validated in a phantom study using cell pellets ranging from 2x105 to 2x106 MSC. Pellets were imaged three times, with the error bars representing the standard deviation between scans. The 19F-MRI quantification is in very strong agreement with the true number of cells, and has a Pearson correlation coefficient of 0.99. The red line represents the ideal result of a 1:1 correlation.
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pone.0118544.g002: In vitro validation of 19F-MRI quantification accuracy.Quantification was validated in a phantom study using cell pellets ranging from 2x105 to 2x106 MSC. Pellets were imaged three times, with the error bars representing the standard deviation between scans. The 19F-MRI quantification is in very strong agreement with the true number of cells, and has a Pearson correlation coefficient of 0.99. The red line represents the ideal result of a 1:1 correlation.

Mentions: Quantification of the 19F signal was tested in vitro using Cell Sense labeled mMSC pellets. Imaging was performed at 9.4T on six cell pellets ranging from 200k to 2 million cells. Fig. 2 represents the average quantification and standard deviation from imaging the cell pellets on three different occasions. We observed a strong linear relationship between the MR quantification and the real cell number, with an R2 = 0.98.


Tracking the fate of stem cell implants with fluorine-19 MRI.

Gaudet JM, Ribot EJ, Chen Y, Gilbert KM, Foster PJ - PLoS ONE (2015)

In vitro validation of 19F-MRI quantification accuracy.Quantification was validated in a phantom study using cell pellets ranging from 2x105 to 2x106 MSC. Pellets were imaged three times, with the error bars representing the standard deviation between scans. The 19F-MRI quantification is in very strong agreement with the true number of cells, and has a Pearson correlation coefficient of 0.99. The red line represents the ideal result of a 1:1 correlation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358825&req=5

pone.0118544.g002: In vitro validation of 19F-MRI quantification accuracy.Quantification was validated in a phantom study using cell pellets ranging from 2x105 to 2x106 MSC. Pellets were imaged three times, with the error bars representing the standard deviation between scans. The 19F-MRI quantification is in very strong agreement with the true number of cells, and has a Pearson correlation coefficient of 0.99. The red line represents the ideal result of a 1:1 correlation.
Mentions: Quantification of the 19F signal was tested in vitro using Cell Sense labeled mMSC pellets. Imaging was performed at 9.4T on six cell pellets ranging from 200k to 2 million cells. Fig. 2 represents the average quantification and standard deviation from imaging the cell pellets on three different occasions. We observed a strong linear relationship between the MR quantification and the real cell number, with an R2 = 0.98.

Bottom Line: The 19F signal decreased over time in both models, with a more rapid decrease in the syngeneic model.In the xenograft model, all mice had detectable signal at endpoint.However, in certain circumstances the transfer of cellular label to other bystander cells may confuse interpretation of the long-term fate of the transplanted cells.

View Article: PubMed Central - PubMed

Affiliation: Imaging Research Laboratories, Robarts Research Institute, London, ON, Canada; Department of Medical Biophysics, University of Western Ontario, London, ON, Canada.

ABSTRACT

Background: In this study we used cellular magnetic resonance imaging (MRI) to detect mesenchymal stem cells (MSC) labeled with a Fluorine-19 (19F) agent. 19F-MRI offers unambiguous detection and in vivo quantification of labeled cells.

Methods: We investigated two common stem cell transplant mouse models: an immune competent, syngeneic transplant model and an immune compromised, xenograft transplant model. 19F labelled stem cells were implanted intramuscularly into the hindlimb of healthy mice. The transplant was then monitored for up to 17 days using 19F-MRI, after which the tissue was excised for fluorescence microscopy and immunohistochemisty.

Results: Immediately following transplantation, 19F-MRI quantification correlated very well with the expected cell number in both models. The 19F signal decreased over time in both models, with a more rapid decrease in the syngeneic model. By endpoint, only 2/7 syngeneic mice had any detectable 19F signal. In the xenograft model, all mice had detectable signal at endpoint. Fluorescence microscopy and immunohistochemistry were used to show that the 19F signal was related to the presence of bystander labeled macrophages, and not original MSC.

Conclusions: Our results show that 19F-MRI is an excellent tool for verifying the delivery of therapeutic cells early after transplantation. However, in certain circumstances the transfer of cellular label to other bystander cells may confuse interpretation of the long-term fate of the transplanted cells.

Show MeSH