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Professor Ken Suzuki

Ken

Professor of Translational Cardiovascular Therapeutics

Centre: Microvascular Research

Email: ken.suzuki@qmul.ac.uk
Telephone: +44(0) 20 7882 8233
Website: https://www.centre-for-microvascular-research.com/suzuki-lab

Profile

ORCID iD: 0000-0002-8970-1553

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, National Heart and Lung Institute, 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 heart diseases, 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 multi-disciplinary group. Suzuki is a former Japan Society for the Promotion of Science Fellow and UK Medical Research Council Senior Fellow. 

Research

Group members

Senior staff: Dr Fiona Lewis-McDougall (Lecturer)
Research Fellows: Dr Kazuya Kobayashi; Dr Tomoya Ito; Dr Elena Tsisanova
PhD student: Mr Emrah Ozcan 

Summary

Suzuki’s research primarily aims to develop innovative therapies, including stem cell therapy, to treat heart attack and other types of heart diseases. There are currently three major research lines in the group.

1. Adult stem cell therapy for myocardial repair

Human organs have distinct types of stem/progenitor cells, named “adult stem cells” or “tissue-resident stem cells”. When collected, expanded, and transplanted, these cells are able to improve cardiac performance and structure by repairing the damaged myocardium primarily through secretion of reparative factors (“paracrine effects”). Suzuki’s 25-year research indicated that allogeneic mesenchymal stromal cells (MSCs) are a most promising cell type for the purpose of clinical success of this approach. His group has been optimising the most effective source of MSCs. His research has identified the issues associated with the current cell-injection methods, including poor donor cell survival and risks of complications such as arrhythmia occurrence and coronary blockage. To solve these limitations, Suzuki’s team developed the innovative cell-delivery route, namely “epicardial placement”. His group optimised this technique by applying a range of distinct biocompatible materials/tissue engineering methods, including the cell-sheet technique, different types of hydrogels, bioengineered membrane, etc.

Current projects include:

  • Translational studies of biomaterial-aided epicardial placement of MSCs, aiming to initiate the first-in-human clinical trial
  • Pre-clinical characterisation of human amnion-derived MSCs and induced pluripotent stem cell (iPSC)-derived MSCs as a donor for clinical cell therapy
  • Mechanistic investigations with focuses on the “primary” and “secondary” paracrine effects induced by MSC therapy
  • Study of the role of tissue-repairing macrophages in the MSC-derived secondary paracrine effect
  • Elucidation of the role of exosomes in MSC-based therapy
  • Application of exosomes for the treatment of heart failure
  • Further improvement of the epicardial placement methods, including biomaterial-aided intrapericardial injection
  • Development of “designer” MSCs, which are genetically engineered to achieve greater therapeutic benefits

2. Tissue-repairing macrophages for the treatment of heart failure and other diseases

Immunity and inflammation play a vital role in development of and recovery from heart failure. Suzuki’s group has investigated the role of high-mobility group protein 1, toll like receptors as well as tissue-repairing (M2-like) macrophages in heart failure. In addition to elucidating their basic molecular/cellular biological characterisation, we challenge to apply these data for the development of innovative therapies of heart failure and other diseases.

Current projects include:

  • Biological and functional characterisation of cardiac M2-like macrophages in the intact and damaged heart
  • Investigation of the role of M2-like macrophages in non-cardiac diseases, including post-operative adhesions
  • Establishment of the ideal production protocol of M2-like macrophages from different tissues and/or iPSCs
  • Development of new cell transplantation therapy using M2-like macrophages for treating/preventing heart failure
  • Development of new technologies, including long-acting IL-4, for the treatment of cardiac and non-cardiac disease through modulating M2-like macrophages

3. Pluripotent stem cell therapy for myocardial regeneration

iPSCs are more promising to achieve myocardial regeneration (generation of new cardiomyocytes), compared to adult stem cells. However, pluripotent cells remain associated with critical issues to attain clinical success, including mass production of high-quality and homogeneous cardiomyocytes and regulation of their 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 have to be overcome. With determination to progress this approach toward clinical application, we currently conduct basics/translational research using these cells as follows:

  • Development of an advanced method to deliver iPSC-derived cardiomyocytes cells to the heart by applying the epicardial placement technique
  • Investigation to elucidate and amplify intra-cardiac migration and integration of cardiomyocytes derived from iPSCs
  • Investigation of differentiation stage-specific abilities of iPSC-derived cardiac cells (committed cardiomyocytes versus cardiac progenitors)
  • Development of new methods to enhance maturation of iPSC-derived cardiomyocytes

Publications

  1. Shiraishi M, Yamaguchi A, Suzuki K. Nrg1/ErbB signaling-mediated regulation of fibrosis after myocardial infarction. FASEB J. 2022;36:e22150.
  2. Fields L, Ito T, Kobayashi K, Ichihara Y, Podaru MN, Hussain M, Yamashita K, Machado V, Lewis-McDougall F, Suzuki K. Epicardial placement of fibrin sealant film-incorporating human mesenchymal stromal cells for the treatment of heart failure: towards clinical translation and mechanistic implication. Mol Ther. 2021;29:2554-70.
  3. Ito T, Shintani Y, Fields L, Shiraishi M, Podaru MN, Kainuma S, Yamashita K, Kobayashi K, Perretti M, Lewis-McDougall F, Suzuki K. Cell barrier function of resident peritoneal macrophages in post-operative adhesions. Nat Commun. 2021;12:2232.
  4. You Y, Kobayashi K, Colak B, Luo P, Cozen E, Fields L, Suzuki K (co-last author), Gautrot J. Engineered cell-degradable poly(2-alkyl-2-oxazoline) hydrogels improve epicardial placement of MSCs by stimulating paracrine signaling for cardiac repair. Biomaterials. 2021;269:120356.
  5. Podaru M, Fields L, Kainuma S, Ichihara Y, Hussain M, Ito T, Kobayashi K, Mathur A, D’Acquisto F, Lewis-McDougall F, Suzuki K. Reparative macrophage transplantation for myocardial repair: a refinement of bone marrow mononuclear cell-based therapy. Basic Res in Cardiol. 2019;114:34.
  6. Kobayashi K, Ichihara Y, Sato N, Umeda N, Fields L, Fukumitsu M, Tago Y, Ito T, Kainuma S, Podaru M, Lewis-McDougall FC, Yamahara K, Suzuki K. On-site fabrication of Bi-layered adhesive mesenchymal stromal cell dressings for the treatment of heart failure. Biomaterials. 2019;209:41-53.
  7. Ichihara Y, Kaneko M, Yamahara K, Koulouroudias M, Sato N, Uppal R, Yamazaki K, Saito S, Suzuki K. Self-assembling peptide hydrogel enables instant epicardial coating of the heart with mesenchymal stromal cells for the treatment of heart failure. Biomaterials. 2018;154:12-23.
  8. Shintani Y, Ito T, Fields L, Shiraishi M, Ichihara Y, Sato N, Podaru M, Kainuma S, Tanaka H, Suzuki K. IL-4 as a repurposed biological drug for myocardial infarction through augmentation of alternatively activated cardiac macrophages: proof-of-concept data in mice. Sci Rep. 2017;7:6877.
  9. 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.
  10. Tano N, Narita T, Kaneko M, Ikebe C, Coppen SR, Campbell NG, Shintani Y, Suzuki K. Epicardial placement of mesenchymal stromal cell-sheets for the treatment of ischaemic cardiomyopathy; in vivo proof-of-concept study. Mol Ther. 2014;22:1864-71. 

Sponsors

Collaborators

Internal

Faculty of Medicine and Dentistry

School of Engineering and Materials and Science

External

  • Dr Satsuki Fukushima and Dr Yasunori Shintani (Japan National Cardiovascular Research Center)
  • Dr Makoto Ikeya and Dr Akitsu Hotta (Kyoto Univ, Japan)
  • Dr Kenichi Yamahara (Hyogo Medical College, Japan)
  • Dr Manabu Shiraishi and Prof Atsushi Yamaguchi (Jichi Univ, Japan)
  • Prof Alvaro Mata (Nottingham Univ, UK)

Teaching

  • BHF 4-year MRes/PhD DTP Board member
  • BSc Pharmacology and Innovative Therapeutics (B211)
  • PhD student supervision (primary and secondary)
  • MRes student supervision
  • OSCE regular examiners

Disclosures

  • 2017-2023 Prof Suzuki has received consultancy funds from Kaneka Corp.
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