NDLI: Longitudinal Monitoring of Stem Cell Grafts In Vivo Using Magnetic Resonance Imaging with Inducible Maga as a Genetic Reporter

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Longitudinal Monitoring of Stem Cell Grafts In Vivo Using Magnetic Resonance Imaging with Inducible Maga as a Genetic Reporter

Content Provider	Ivyspring International Publisher
Author	Cho, In K. Moran, Sean P. Paudyal, Ramesh Piotrowska-Nitsche, Karolina Cheng, Pei-Hsun Zhang, Xiaodong Mao, Hui Chan, Anthony W.S.
Editor	Chen, Xiaoyuan (Shawn)
Abstract	Purpose: The ability to longitudinally monitor cell grafts and assess their condition is critical for the clinical translation of stem cell therapy in regenerative medicine. Developing an inducible genetic magnetic resonance imaging (MRI) reporter will enable non-invasive and longitudinal monitoring of stem cell grafts in vivo. Methods: MagA, a bacterial gene involved in the formation of iron oxide nanocrystals, was genetically modified for in vivo monitoring of cell grafts by MRI. Inducible expression of MagA was regulated by a Tet-On (Tet) switch. A mouse embryonic stem cell-line carrying Tet-MagA (mESC-MagA) was established by lentivirus transduction. The impact of expressing MagA in mESCs was evaluated via proliferation assay, cytotoxicity assay, teratoma formation, MRI, and inductively coupled plasma atomic emission spectroscopy (ICP-OES). Mice were grafted with mESCs with and without MagA (mESC-MagA and mESC-WT). The condition of cell grafts with induced “ON” and non-induced “OFF” expression of MagA was longitudinally monitored in vivo using a 7T MRI scanner. After imaging, whole brain samples were harvested for histological assessment. Results: Expression of MagA in mESCs resulted in significant changes in the transverse relaxation rate (R2 or 1/T2) and susceptibility weighted MRI contrast. The pluripotency of mESCs carrying MagA was not affected in vitro or in vivo. Intracranial mESC-MagA grafts generated sufficient T2 and susceptibility weighted contrast at 7T. The mESC-MagA grafts can be monitored by MRI longitudinally upon induced expression of MagA by administering doxycycline (Dox) via diet. Conclusion: Our results demonstrate MagA could be used to monitor cell grafts noninvasively, longitudinally, and repetitively, enabling the assessment of cell graft conditions in vivo.
Related Links	https://www.thno.org/v04p0972.pdf
Ending Page	989
Starting Page	972
File Format	PDF
ISSN	18387640
DOI	10.7150/thno.9436
Journal	Theranostics
PubMed reference number	25161700
Issue Number	10
PubMed Central reference number	PMC4143941
Volume Number	4
Language	English
Publisher	Ivyspring International Publisher
Publisher Date	2014-07-27
Access Restriction	Open
Subject Keyword	Magnetic resonance imaging Reporter gene MagA Longitudinal monitoring Stem cell Cell tracking Regenerative medicine Inducible expression Intracranial graft Research Paper
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology Medicine
Journal Impact Factor	13.3

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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Longitudinal Monitoring of Stem Cell Grafts In Vivo Using Magnetic Resonance Imaging with Inducible Maga as a Genetic Reporter

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