Professor Ken Suzuki

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