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Scientific Persistence in the Tradition of Lister

Lin on bike

Ren-Ke Li

Lister Prize winner Ren-Ke Li received his medical degree from Harbin Medical University, and his Master’s and PhD degrees in Clinical Biochemistry from the University of Toronto. He is currently Canadian Research Chair in cardiac regeneration. His Lister Prize Lecture was entitled Cardiac Regeneration.

In his award presentation Ren-Ke first expressed deep appreciation for the niche that this Department of Surgery provided for him as a researcher. He joined the Department of Surgery 20 years ago at Toronto General Hospital and embarked on a research career focused on cardiac regeneration. He divided his research report into three parts. Cell transplantation for cardiac repair was built on the hypothesis that healthy muscle cells injected into damaged cardiac tissue might improve function. Using a left anterior descending artery ligation model in rats, he showed that cardiac function could be improved by implanted cells. Paul Fedak, whose picture was the first of the several residents in his slides, found that the graft restores matrix integrity to the heart.

Lin on bike

With Dr. TianBiao Liu, he demonstrated that there was improved heart cell survival related to the angiogenesis that was induced. Based on this work and other supporting information, Philippe Menasché, our 2012 Gallie Day lecturer, injected skeletal muscle cells from patients into their revascularized hearts to improve function. A randomized controlled trial confirmed that this treatment was not effective in humans.

The second phase of the research involved the use of stem cells for cardiac regeneration. Shinji Tomita, a post- doctoral student in Ren-Ke’s lab, found that bone marrow stem cells can improve function in infarcted rat hearts. He also used endothelial progenitors imported from Germany to revascularize the ischemic porcine heart of a preclinical study model. Though preclinical improvement was demonstrated, clinical improvement did not follow. Ren–Ke analyzed this carefully and realized that the age of the cells might be the critical factor. The animals in laboratory studies were young, but human patients with infarcts are not. In a 4 by 4 analysis, he then compared old cells and young cells in old and young recipients. Young recipients gave the best results, so it was clear that the environment was a key factor- the niche into which the cells were injected. When undifferentiated stem cells were used, rejection was delayed until they differentiated, but eventually they too were rejected.

Since exogenous stem cells could not repair and regenerate injured heart tissue, Ren-Ke’s research group initiated a third phase of research, Cardiac Rejuvenation. Shafie Fazel, during his highly productive PhD studies, replaced the bone marrow of older mice with young marrow. The young marrow cells migrated to the heart, so that they could not only create a stem cell niche even in older recipients, but enhance heart repair after infarction. Ren-Ke next performed a subtraction experiment, radiating the bone marrow but not the heart after bone marrow transplantation. The young bone marrow cells in old recipients restored heart function, proving that the young stem cells in heart are required to rejuvenate the aged heart. From cardiac repair to cardiac regeneration to cardiac rejuvenation, Ren-Ke has dedicated his research to restoration of cardiac function. He believes that “Bone marrow cells are the key. They will rejuvenate the stroma of recipients.”

This thoughtful and methodical series of studies was appropriately associated through this award with the name and work of Joseph Lister (1827-1912), a remarkably scholarly and persistent student of surgical infection and antisepsis.


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