Prof of Translational Cardiovascular Therapeutics (Hon Consultant, Cardiac Surgery, Barts NHS Trust)
Ken Suzuki is a clinical academic in the field of cardiac surgery, initially trained at Osaka University, Japan. Following the 10-year clinical training and a PhD awarded for his work on gene therapy for myocardial ischaemia-reperfusion injury, he was recruited to the Harefield Heart Science Centre, Imperial College London (head; Prof Sir Magdi Yacoub) in 1998. In this Centre of excellence, he completed a series of research projects on stem cell therapy and gene therapy for treating heart disease, in parallel to his surgical training. Subsequently Suzuki took up the chair of a new research group within the William Harvey Research Institute in 2007. Here, he continues basic, translational, pre-clinical, and clinical cardiovascular research, which aims to develop innovative therapies for heart failure, with a well-balanced, multi-disciplinary group. Suzuki is a former Japan Society for the Promotion of Science Fellow and UK Medical Research Council Senior Fellow. He is currently a Collaborative Professor of Osaka University, Japan.
Summary of Research
Suzuki’s research primarily aims to develop innovative therapies, including stem cell and regenerative therapy, to treat chronic heart failure, myocardial infarction as well as ischaemia-reperfusion injury. There are currently three major research lines in the group.
1. Adult stem cell therapy for myocardial repair: Adult stem/progenitor cells are able to improve cardiac performance and structure by repairing the damaged myocardium primarily through secretion of reparative factors (paracrine effects). Suzuki’s 18-year research suggested that allogeneic mesenchymal stromal cells are the most promising cell type for this approach to be a clinically successful. He has also clarified the issues associated with the current cell-delivery methods (i.e. intramyocardial and intracoronary injection), including poor donor cell engraftment and risks of complications such as arrhythmia occurrence and coronary embolism. To solve these limitations, he has developed a safer and more effective cell-delivery approach, “epicardial placement” by using biocompatible materials/tissue engineering. This project is funded by BHF Programme Grant and company co-development funds including Kaneka Corporation (Japan). Current projects include:
- Translational and pre-clinical studies for development of biomaterial-aided epicardial placement of mesenchymal stromal cells. Suzuki aims to translate this innovative approach to the first-in-human clinical application in 2017/2018.
- Pre-clinical characterisation for safety and effectiveness of human amnion-derived mesenchymal stromal cells as a donor for cell therapy.
- Study of the potential of biomaterials to enhance cellular properties of stem cells.
- Mechanistic investigations with focuses on the direct and indirect paracrine effects by mesenchymal stromal cell therapy.
- Development of novel biocompatible materials for stem cell therapy (collaborative project with the Institute of Bioengineering in QMUL).
2. Alternatively activated macrophages for the treatment of heart failure and other diseases: Immunity and inflammation play an vital role in development of and recovery from heart failure. Suzuki’s group has investigated the role of high-mobility group protein 1
(HMGB-1), toll like receptors (TLRs) as well as cardiac alternatively-activated (M2) macrophages in heart failure. In addition to elucidating their basic molecular/cellular biological aspects, we challenge to apply these data for development of innovative therapies of heart failure and other diseases. These projects are funded by the Heart Research UK and Queen Mary Innovation. Current projects include:
- Biological and functional characterisation of cardiac M2 macrophages in the intact and damaged heart.
- Investigation of the role of M2 macrophages in non-cardiac diseases.
- Development of new therapeutic approaches, including long-acting IL-4, for treating/preventing heart failure by modulating M2 macrophages.
- Development of new therapeutic approaches for treating/preventing other cardiac and non-cardiac diseases by modulating M2 macrophages.
- In vitro production and characterisation of M2 macrophages.
- Improvement of bone marrow mononuclear cell transplantation therapy by regulating differentiation of the donor cells to a specific macrophage phenotype.
3. Pluripotent stem cell therapy for myocardial regeneration: Embryonic stem cells and induced pluripotent stem cells are more promising to achieve myocardial regeneration (generation of new cardiomyocytes), compared to adult stem cells. However, these pluripotent cells remain associated with critical issues to initiate clinical application, including mass production of high-quality cells and regulation of cardiomyogenic differentiation (i.e. avoidance of tumour formation). In addition, insufficient maturation and inappropriate integration of stem cell-derived cardiomyocytes as well as suboptimal cell-delivery method into the heart have to be overcome. With firm determination to progress this approach toward clinical application, we currently conduct basics/translational research of these cells (with fund from BHF Programme Grant and Japan Society for Promotion of Science Fellowship):
- Development of an advanced method to deliver stem cells-derived cardiac progenitor cells or cardiomyocytes into the heart by applying above epicardial placement technique.
- Investigation to understand and amplify intra-cardiac migration and integration of cardiomyocytes (or cardiac progenitors) derived from stem cells.
Members of the Group
Senior Staff: Non-clinical Lecturer under recruitment
Research Fellows: Dr Yuki Ichihara, Dr Laura Field, Dr Nobuhiko Sato, Dr Tomoya Ito, Dr Satoshi Kainuma
PhD Student: Miss Yaqi You, Mr Mihai Podaru, Miss Eithne Maguire.
1. Shiraishi M, Shintani Ya, Shintani Yu, Ishida H, Saba R, Yamaguchi A, Adachi H, Yashiro K, Suzuki K. Alternatively activated macrophages determine repair of the infarcted adult murine heart. J Clin Invest. 2016;126:2151-66.
2. Ishida H, Saba R, Ioannis Kokkinopoulos 1,3, Hashimoto M, Yamaguchi O, Nowotschin S, Shiraishi M, Ruchaya P, Miller D, Harmer S, Poliandri A, Kogaki S, Sakata Y, Dunkel L, Tinker A, Hadjantonakis A, Sawa Y, Sasaki H, Ozono K, Suzuki K, Yashiro K. GFRA2 identifies cardiac progenitors and mediates cardiomyocyte differentiation in a RET-independent signalling pathway. Cell Report. 2016:16:1026-38.
3. Tano N, Kaneko M, Ichihara Y, Ikebe C, Coppen SR, Shiraishi M, Shintani Y, Yashiro K, Warrens A, Suzuki K. Allogeneic mesenchymal stromal cells transplanted onto the heart surface achieve therapeutic myocardial repair despite immunologic responses in rats. J Am Heart Assoc. 2016;5:e002815.
4. Sawhney V, Campbell NG, Brouilette SW, Coppen SR, Harbo M, Baker V, Ikebe C, Shintani Y, Hunter RJ, Dhinoja M, Johnston A, Earley MJ, Sporton S, Bendix L, Suzuki K, Schilling RJ. Telomere shortening and telomerase activity in ischaemic cardiomyopathy patients - Potential markers of ventricular arrhythmia. Int J Cardiol. 2016;207:157-63.
5. Campbell N, Kaneko M, Shintani Y, Narita T, Sawhney V, CoppenSR, YashiroK, Mathur A, Suzuki K. Cell size critically determines initial retention of bone marrow mononuclear cells in the heart after intracoronary injection: evidence from a rat model. PLoS ONE. 2016;11:e0158232.
6. Narita T, Suzuki K. Bone marrow-derived mesenchymal stem cells for the treatment of heart failure. Heart Fail Rev. 2015;20:53-68.7. Tano N, Narita T, KanekoM, IkebeC, CoppenSR, CampbellNG, ShintaniY, SuzukiK. Epicardial placement of scaffold-free mesenchymal stromal cell-sheets for the treatment of ischemic cardiomyopathy; in vivo proof-of-concept study. Mol Ther. 2014;22:1864-71.
7. Tano N, Narita T, Kaneko M, IkebeC, CoppenSR, Campbell NG, Shintani Y, Suzuki K. Epicardial placement of scaffold-free mesenchymal stromal cell-sheets for the treatment of ischemic cardiomyopathy; in vivo proof-of-concept study. Mol Ther. 2014;22:1864-71.
8. Shintani Y, Drexler HC, Kioka H, Terracciano CM, Coppen SR, Imamura H, Akao M, Nakai J, Wheeler AP, Higo S, Nakayama H, Takashima S, Yashiro K, Suzuki K. Toll-like receptor 9 protects non-immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA2. EMBO Rep. 2014;15:438-45.
9. Shintani Y, Kapoor A, Kaneko M, Smolenski RT, D’Acquisto F, Coppen S R, ThiemermannC, Takashima S, Yashiro K, Suzuki K. TLR9 mediates cellular protection by modulating energy metabolism in cardiomyocytes and neurons. Proc Nat Acad Sci USA. 2013;110:5109-14.
10. Narita T, Shintani Y, Ikebe C, Kaneko M, Campbell N G, Coppen S R, Uppal R, Sawa Y, Yashiro K, Suzuki K. The use of scaffold-free cell sheet technique to refine mesenchymal stromal cell-based therapy for heart failure. Mol Ther. 2013;21:860-7.