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Date: 8 October 2024 (Tuesday)
Time: 11:00am - 12:30pm (SGT) Format: Virtual (Zoom) Hosted by: Adrian TEO, IMCB, Singapore |
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Speakers' information
Masaki IEDA Department of Cardiology, Keio University School of Medicine, Japan "Direct cardiac reprogramming to treat heart failure" |
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ABSTRACT
Heart failure increases as a cause of mortality, and regenerative therapy is highly demanded. We demonstrated that cardiac transcription factors, Gata4, Mef2c, and Tbx5 (GMT), directly reprogrammed fibroblasts into cardiomyocytes (Ieda et al., Cell 2010). Gene delivery of vectors expressing GMT in the mouse infarct hearts converted resident cardiac fibroblasts into cardiomyocytes and improved cardiac function in acute MI. We confirmed that GMT gene delivery could repair infarct hearts mainly via bona-fide cardiac reprogramming rather than cell fusion. We recently found that direct reprogramming improved cardiac function and reverses fibrosis in chronic MI (Tani et al., Circulation 2023). Although many challenges remain, cardiac reprogramming may open new avenues for the treatment of heart failure.
BIO
Masaki Ieda is a Professor and Chair in the Department of Cardiology, Keio University School of Medicine in Japan. He obtained his MD and PhD from Keio University School of Medicine in Tokyo in 1995 and 2005, respectively. Dr Ieda then became a Postdoc in the Deepak Srivastava lab at the Gladstone Institute in San Francisco from 2007 to study cardiac regeneration. Dr Ieda was the first to demonstrate direct cardiac reprogramming as published in Cell in 2010. Then, He returned to Japan to become an Associate Professor in Keio Universit and a Research Director of the Japan Science and Technology Agency-CREST. He became a Professor and Chair in the Department of Cardiology, Faculty of Medicine, University of Tsukuba in 2018, and then moved to the current position in 2023.
Heart failure increases as a cause of mortality, and regenerative therapy is highly demanded. We demonstrated that cardiac transcription factors, Gata4, Mef2c, and Tbx5 (GMT), directly reprogrammed fibroblasts into cardiomyocytes (Ieda et al., Cell 2010). Gene delivery of vectors expressing GMT in the mouse infarct hearts converted resident cardiac fibroblasts into cardiomyocytes and improved cardiac function in acute MI. We confirmed that GMT gene delivery could repair infarct hearts mainly via bona-fide cardiac reprogramming rather than cell fusion. We recently found that direct reprogramming improved cardiac function and reverses fibrosis in chronic MI (Tani et al., Circulation 2023). Although many challenges remain, cardiac reprogramming may open new avenues for the treatment of heart failure.
BIO
Masaki Ieda is a Professor and Chair in the Department of Cardiology, Keio University School of Medicine in Japan. He obtained his MD and PhD from Keio University School of Medicine in Tokyo in 1995 and 2005, respectively. Dr Ieda then became a Postdoc in the Deepak Srivastava lab at the Gladstone Institute in San Francisco from 2007 to study cardiac regeneration. Dr Ieda was the first to demonstrate direct cardiac reprogramming as published in Cell in 2010. Then, He returned to Japan to become an Associate Professor in Keio Universit and a Research Director of the Japan Science and Technology Agency-CREST. He became a Professor and Chair in the Department of Cardiology, Faculty of Medicine, University of Tsukuba in 2018, and then moved to the current position in 2023.
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Lynn YAP
Lee Kong Chian School of Medicine (LKCM), Singapore National Heart Research Institute Singapore "Insights into hPSC-derived cardiac progenitors for heart regeneration" |
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ABSTRACT
Regenerative cardiology with stem cell-derived cardiovascular progenitors (CVPs) is a potential approach to regenerate infarcted myocardial tissue. We have differentiated pluripotent human embryonic stem cells (hESCs) to CVPs on a laminin LN521+LN221 matrix under fully reproducible human-derived, chemically defined, xeno-free conditions and transplanted them into the infarcted pigs' hearts. The non-contractile CVPs engrafted and proliferated in the infarction site. The heart ejection fraction has been shown to increase from 40% to 60% and we also measured a significantly lower extracellular matrix protein expression contributing to the reduction in fibrosis. Importantly, none of the animals developed lethal arrhythmia. Furthermore, using spatial transcriptomics revealed that the human graft exhibited high transcriptional reproducibility expressing markers of mature cardiomyocytes such as metabolic, ribosomal, T-tubule, and channel-related genes over time. Suggesting the viability, efficacy, and functionality of mature human CM in regenerating infarcted hearts.
BIO
Lynn Yap is an assistant professor at the Lee Kong Chian School of Medicine at Nanyang Technological University, Singapore, and the National Heart Research Institute Singapore. She holds a. Ph.D. in Integrative Sciences and Engineering focusing on extracellular matrix proteins and stem cell biology. She is the principal investigator and directs a regenerative cardiology and cardiometabolic medicine group. The overall goal of her research program is to uncover the molecular and physiological mechanisms underpinning stem cell-based therapy for regenerative cardiology. She co-invented laminin cardiac technology and demonstrated the potential of cardiac progenitors in regenerating myocardial infarction preclinical models. She received the Khoo Teck Puat post-doctoral fellowship, the Goh cardiovascular research award, and a theme PI in the National Research Foundation Competitive Research Programme. She is a member of the International Society of Stem Cell Research (ISSCR), American Heart Association (AHA), Stem Cell Society Singapore (SCSS), Early Career Advisory Group for eLife Sciences Publications (ECAG), LKC@Women in Science, and a co-founder of Alder Therapeutics.
Regenerative cardiology with stem cell-derived cardiovascular progenitors (CVPs) is a potential approach to regenerate infarcted myocardial tissue. We have differentiated pluripotent human embryonic stem cells (hESCs) to CVPs on a laminin LN521+LN221 matrix under fully reproducible human-derived, chemically defined, xeno-free conditions and transplanted them into the infarcted pigs' hearts. The non-contractile CVPs engrafted and proliferated in the infarction site. The heart ejection fraction has been shown to increase from 40% to 60% and we also measured a significantly lower extracellular matrix protein expression contributing to the reduction in fibrosis. Importantly, none of the animals developed lethal arrhythmia. Furthermore, using spatial transcriptomics revealed that the human graft exhibited high transcriptional reproducibility expressing markers of mature cardiomyocytes such as metabolic, ribosomal, T-tubule, and channel-related genes over time. Suggesting the viability, efficacy, and functionality of mature human CM in regenerating infarcted hearts.
BIO
Lynn Yap is an assistant professor at the Lee Kong Chian School of Medicine at Nanyang Technological University, Singapore, and the National Heart Research Institute Singapore. She holds a. Ph.D. in Integrative Sciences and Engineering focusing on extracellular matrix proteins and stem cell biology. She is the principal investigator and directs a regenerative cardiology and cardiometabolic medicine group. The overall goal of her research program is to uncover the molecular and physiological mechanisms underpinning stem cell-based therapy for regenerative cardiology. She co-invented laminin cardiac technology and demonstrated the potential of cardiac progenitors in regenerating myocardial infarction preclinical models. She received the Khoo Teck Puat post-doctoral fellowship, the Goh cardiovascular research award, and a theme PI in the National Research Foundation Competitive Research Programme. She is a member of the International Society of Stem Cell Research (ISSCR), American Heart Association (AHA), Stem Cell Society Singapore (SCSS), Early Career Advisory Group for eLife Sciences Publications (ECAG), LKC@Women in Science, and a co-founder of Alder Therapeutics.