Multimodal Imaging for In Vivo Evaluation of Induced Pluripotent Stem Cells in a Murine Model of Heart Failure.
Myocardial stem cell therapy in heart failure is strongly dependent on successful cellular transfer, engraftment, and survival. Moreover, massive cell loss directly after intramyocardial injection is commonly observed, generating the need for efficient longitudinal monitoring of transplanted cells in order to develop more efficient transplantation techniques. Therefore, the aim of the present study was to assess viability and cardiac retention of induced pluripotent stem cells after intramyocardial delivery using in vivo bioluminescence analysis (BLI) and magnetic resonance imaging (MRI). Murine induced pluripotent stem cells (iPSCs) were transfected for luciferase reporter gene expression and labeled intracellularly with supraparamagnetic iron oxide particles. Consequently, 5 × 105cells were transplanted intramyocardially following left anterior descending coronary artery ligation in mice. Cardiac iPSCs were detected using BLI and serial T2* sequences by MRI in a 14-day follow-up. Additionally, infarct extension and left ventricular (LV) function were assessed by MRI. Controls received the same surgical procedure without cell injection. MRI sequences showed a strong MRI signal of labeled iPSCs correlating with myocardial late enhancement, demonstrating engraftment in the infarcted area. Mean iPSC volumes were 4.2 ± 0.4 mm3at Day 0; 3.1 ± 0.4 mm3at Day 7; and 5.1 ± 0.8 mm3after 2 weeks. Thoracic BLI radiance decreased directly after injection from 1.0 × 106± 4.2 × 104(p/s/cm2/sr) to 1.0 × 105± 4.9 × 103(p/s/cm2/sr) on Day 1. Afterward, BLI radiance increased to 1.1 × 106± 4.2 × 104(p/s/cm2/sr) 2 weeks after injection. Cardiac graft localization was confirmed by ex vivo BLI analysis and histology. Left ventricular ejection fraction was higher in the iPSC group (30.9 ± 0.9%) compared to infarct controls (24.0 ± 2.1%; P < 0.05). The combination of MRI and BLI assesses stem cell fate in vivo, enabling cardiac graft localization with evaluation of LV function in myocardial infarction.
Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School.|Leibniz Research Laboratories for Biotechnology and Artificial Organs-REBIRTH-Cluster of Excellence, Hannover Medical School.
Sebastian V
SV
Rojas
Central Animal Laboratory, Hannover Medical School, Hannover.
Martin
M
Meier
Leibniz Research Laboratories for Biotechnology and Artificial Organs-REBIRTH-Cluster of Excellence, Hannover Medical School.
Robert
R
Zweigerdt
Miltenyi Biotec GmbH, Bergisch Gladbach.
Dominik
D
Eckardt
Leibniz Research Laboratories for Biotechnology and Artificial Organs-REBIRTH-Cluster of Excellence, Hannover Medical School.
Christian
C
Rathert
Leibniz Research Laboratories for Biotechnology and Artificial Organs-REBIRTH-Cluster of Excellence, Hannover Medical School.
Natalie
N
Schecker
Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School.
Jan D
JD
Schmitto
Department of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany.
Sara
S
Rojas-Hernandez
Leibniz Research Laboratories for Biotechnology and Artificial Organs-REBIRTH-Cluster of Excellence, Hannover Medical School.
Ulrich
U
Martin
Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School.
Ingo
I
Kutschka
Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School.|Leibniz Research Laboratories for Biotechnology and Artificial Organs-REBIRTH-Cluster of Excellence, Hannover Medical School.
Axel
A
Haverich
Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School.|Leibniz Research Laboratories for Biotechnology and Artificial Organs-REBIRTH-Cluster of Excellence, Hannover Medical School.
Andreas
A
Martens
D000818:Animals; D002478:Cells, Cultured; D006321:Heart / Q000000981:diagnostic imaging*; D006333:Heart Failure / Q000000981:diagnostic imaging* / Q000628:therapy*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D008163:Luminescent Measurements / Q000379:methods; D008279:Magnetic Resonance Imaging; D051379:Mice; D064847:Multimodal Imaging / Q000379:methods; D009206:Myocardium / Q000473:pathology; D061848:Optical Imaging / Q000379:methods
Bioluminescence imaging; Induced pluripotent stem cells; Magnetic resonance imaging; Myocardial infarction; Stem cell therapy