- Walking poster presentation
- Open Access
In vivo multi-modality tracking of the regenerative effects of the human induced pluripotent stem cell-derived cardiomyocytes (iCMs)
© Mahmoudi et al; licensee BioMed Central Ltd. 2015
- Published: 3 February 2015
- Thymidine Kinase
- Myocardial Viability
- Zinc Finger Nuclease
- Herpes Simplex Virus Thymidine Kinase
- Injured Myocardium
In vivo multi-modality cellular and molecular imaging of the engrafted iCMs is necessary to characterize the engraftment and the regional effects on the viability of the injured myocardium. Zinc finger nuclease (ZFN)-mediated integration of the reporter gene into the AAVS1 locus in the iCMs and manganese enhanced MRI (MEMRI) should allow precise in vivo detection of myocardial regeneration.
In order to have multi-modal in vivo imaging of the stem cells, ZFN technology was employed to integrate a triple fusion RG (firefly luciferase (BLI), red fluorescent protein (RFP), and herpes simplex virus thymidine kinase (PET)) into the AAVS1 locus of iPSCs. iPSCs monoclonal lines were then differentiated into iCMs, under chemically defined conditions using CHIR (4 µM) and C59 (2 µM) small molecules to modulate the Wnt pathway activity. The produced iCMs were then fully characterized and injected into mice and tracked with several techniques.
This study demonstrates the successful use of in vivo multi-modality imaging to confirm the regeneration of the injured myocardium. ZFN technology enables targeted site-specific insertion of RGs and MEMRI allows direct evaluation of myocardial viability. These imaging capabilities will allow clinical translation of iCMs.
NIH/NHLBI UM1 (HL-12-026).
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.