Novel MRI Contrast Agent from Magnetotactic Bacteria Enables In Vivo Tracking of iPSC-derived Cardiomyocytes.
Therapeutic delivery of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) represents a novel clinical approach to regenerate the injured myocardium. However, methods for robust and accurate in vivo monitoring of the iCMs are still lacking. Although superparamagnetic iron oxide nanoparticles (SPIOs) are recognized as a promising tool for in vivo tracking of stem cells using magnetic resonance imaging (MRI), their signal persists in the heart even weeks after the disappearance of the injected cells. This limitation highlights the inability of SPIOs to distinguish stem cell viability. In order to overcome this shortcoming, we demonstrate the use of a living contrast agent, magneto-endosymbionts (MEs) derived from magnetotactic bacteria for the labeling of iCMs. The ME-labeled iCMs were injected into the infarcted area of murine heart and probed by MRI and bioluminescence imaging (BLI). Our findings demonstrate that the MEs are robust and effective biological contrast agents to track iCMs in an in vivo murine model. We show that the MEs clear within one week of cell death whereas the SPIOs remain over 2 weeks after cell death. These findings will accelerate the clinical translation of in vivo MRI monitoring of transplanted stem cell at high spatial resolution and sensitivity.
Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA.|Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Morteza
M
Mahmoudi
Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA.
Atsushi
A
Tachibana
Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
Andrew B
AB
Goldstone
Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA.
Y Joseph
YJ
Woo
Bell Biosystems Inc., San Francisco, CA 94107, USA.
Papia
P
Chakraborty
Bell Biosystems Inc., San Francisco, CA 94107, USA.
Kayla R
KR
Lee
Bell Biosystems Inc., San Francisco, CA 94107, USA.
Chandler S
CS
Foote
Bell Biosystems Inc., San Francisco, CA 94107, USA.
Stephanie
S
Piecewicz
Bell Biosystems Inc., San Francisco, CA 94107, USA.
Joyce C
JC
Barrozo
Bell Biosystems Inc., San Francisco, CA 94107, USA.
Abdul
A
Wakeel
Bell Biosystems Inc., San Francisco, CA 94107, USA.
Bradley W
BW
Rice
Bell Biosystems Inc., San Francisco, CA 94107, USA.
Caleb B
CB
Bell Iii
Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA.
Phillip C
PC
Yang
D000818:Animals; D001419:Bacteria; D058948:Cell Tracking; D003287:Contrast Media / Q000008:administration & dosage*; D006321:Heart / Q000000981:diagnostic imaging*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology; D058185:Magnetite Nanoparticles / Q000008:administration & dosage*; D008297:Male; D016513:Mice, SCID; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000502:physiology* / Q000637:transplantation; D051381:Rats; D013559:Symbiosis
D003287:Contrast Media; D058185:Magnetite Nanoparticles