Author + information
- Received May 9, 2019
- Revision received August 20, 2019
- Accepted August 24, 2019
- Published online December 23, 2019.
- Borami Shin, MDa,b,
- Mossab Y. Saeed, MDa,b,
- Jesse J. Esch, MDb,c,
- Alvise Guariento, MDa,b,
- David Blitzer, MDa,b,
- Kamila Moskowitzova, MDa,b,
- Giovanna Ramirez-Barbieri, MDa,b,
- Arzoo Orfany, MDa,b,
- Jerusha K. Thedsanamoorthy, BAb,d,
- Douglas B. Cowan, PhDb,d,
- James A. Inkster, PhDb,e,
- Erin R. Snay, BRSe,
- Steven J. Staffa, MSb,d,
- Alan B. Packard, PhDb,d,
- David Zurakowski, PhDb,d,
- Pedro J. del Nido, MDa,b and
- James D. McCully, PhDa,b,∗ ()
- aDepartment of Cardiac Surgery, Boston Children’s Hospital, Boston, Massachusetts
- bHarvard Medical School, Boston, Massachusetts
- cDepartment of Cardiology, Boston Children’s Hospital, Boston, Massachusetts
- dDepartment of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Boston, Massachusetts
- eDivision of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston Children’s Hospital, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. James D. McCully, Department of Cardiac Surgery, Boston Children’s Hospital, 300 Longwood Avenue, Enders-407, Boston, Massachusetts 02115.
• Mitochondrial transplantation uses mitochondria isolated from the patient’s own body to replace or augment native mitochondria damaged by ischemia reperfusion injury.
• The transplanted mitochondria can be delivered to the myocardium by intra-coronary injection.
• Intracoronary injection of mitochondria is safe and has no effect on coronary patency.
• Intracoronary injection of mitochondria provides for the rapid uptake and specific biodistribution of mitochondria throughout the heart.
• Intracoronary mitochondrial transplantation is efficacious and provides for enhanced post-ischemic myocardial function, improved coronary blood flow and reduction of infarct size.
Mitochondrial dysfunction is the determinant insult of ischemia-reperfusion injury. Autologous mitochondrial transplantation involves supplying one’s healthy mitochondria to the ischemic region harboring damaged mitochondria. The authors used in vivo swine to show that mitochondrial transplantation in the heart by intracoronary delivery is safe, with specific distribution to the heart, and results in significant increase in coronary blood flow, which requires intact mitochondrial viability, adenosine triphosphate production, and, in part, the activation of vascular KIR channels. Intracoronary mitochondrial delivery after temporary regional ischemia significantly improved myocardial function, perfusion, and infarct size. The authors concluded that intracoronary delivery of mitochondria is safe and efficacious therapy for myocardial ischemia-reperfusion injury.
This study was supported by the Richard A. and Susan F. Smith President’s Innovation Award, The Sidman Family Foundation, The Michael B. Rukin Charitable Foundation, The Kenneth C. Griffin Charitable Research Fund, and The Boston Investment Conference. Dr. Shen was supported by National Institutes of Health (NIH) grant 5T32HL007734. The synthesis of 18F-rhodamine-6G was supported by NIH grant 5 RO1 HL108107. Drs. del Nido and McCully have patents pending for the isolation and usage of mitochondria. The authors have reported that that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received May 9, 2019.
- Revision received August 20, 2019.
- Accepted August 24, 2019.
- 2019 The Authors