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J Magn Reson Imaging. 2016 Dec;44(6):1456-1463. doi: 10.1002/jmri.25299. Epub 2016 May 17.

Positive-contrast cellular MRI of embryonic stem cells for tissue regeneration using a highly efficient T1 MRI contrast agent.

Loai S1,2,3, Haedicke I4,5, Mirzaei Z1,2, Simmons CA1,2,6, Zhang XA4,5, Cheng HL1,2,7.

Author information

1
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
2
Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada.
3
Department of Chemical Engineering and Bioengineering, McMaster University, Hamilton, ON, Canada.
4
Department of Physical and Environmental Sciences, University of Toronto Scarborough, Toronto, ON, Canada.
5
Department of Chemistry, University of Toronto, Toronto, ON, Canada.
6
Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON, Canada.
7
The Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto Toronto, ON, Canada.

Abstract

PURPOSE:

To investigate the feasibility of high-sensitivity cellular MRI of embryonic stem (ES) cells using a novel cell permeable and cell retentive T1 contrast agent.

MATERIALS AND METHODS:

Mouse ES cells were labeled with a novel manganese porphyrin contrast agent, MnAMP, at 0.1 mM over 2 to 24 h and retained in contrast-free medium for up to 24 h postlabeling. MRI was performed on a 3 Tesla clinical scanner; T1 and T2 relaxation times were measured. Quantification of manganese content was performed using atomic absorption spectroscopy. Viability and proliferation assays were done for the longest labeling interval. Differentiation capacity was assessed using the hanging drop method to direct differentiation toward cardiomyocytes.

RESULTS:

MnAMP-labeled ES cells exhibited over a fourfold decrease in T1 compared with unlabeled cells, and maintained up to a threefold decrease 24 h postlabeling. Viability and proliferation were not affected. Most importantly, labeled ES cells differentiated into functional cardiomyocytes that exhibited normal contractility patterns.

CONCLUSION:

MnAMP-based cellular MRI is a very high sensitivity T1 approach for cellular imaging. It has the potential for noninvasive in vivo monitoring of stem cell therapy in cardiac regeneration and other tissue engineering and regenerative medicine applications. J. Magn. Reson. Imaging 2016;44:1456-1463.

KEYWORDS:

cardiomyocytes; cellular imaging and cell tracking; embryonic stem cells; regenerative medicine; stem cell therapy; tissue engineering

PMID:
27185221
DOI:
10.1002/jmri.25299
[Indexed for MEDLINE]

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