Scientific Persistence in the Tradition of Lister
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.
|
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.
M.M.
|