Download Stem cell therapy

Stem cell therapy: what a
cardiologist needs to know
Robert Roberts MD
Chief of Cardiology
Baylor College of Medicine
Houston, Texas
Piero Anversa MD
Director, Cardiovascular Research Institute
New York Medical College
Valhalla, New York
Seigo Izumo MD
Professor of Medicine
Harvard Medical School
Boston, Massachusetts
Stem cell therapy
in vitro fertilized embryo
The basics
stem cells
 are primitive cells
 can renew
themselves
multiple embryos
produced in vitro
for clinical purposes
donated surplus embryos
used to culture embryonic
stem cells
Source: University of Wisconsin
 can develop into
different cell types
 have the potential
to become more
differentiated cells
Stem cell therapy
Embryonic stem cells
derived from the early embryo
are totipotent (can differentiate into all
cell types of all organs)
used to create gene knockout (KO) animal
models for CVD study
KO mouse (©Taconic)
Stem cell therapy
Adult stem cells
reside in adult tissue
are multipotent (differentiating capacity
is more limited)
 satellite cells in skeletal muscle
regenerate muscle after injury
 stem cells in bone marrow replenish
blood cells and have potential to
become cardiovascular cells
Stem cell therapy
Body cells
number of cells in the human body:
200 trillion
number of unique cell types all derived from
an estimated 20–30 stem cells: 200
Stem cell therapy
Plasticity
plasticity of adult stem cells much greater
than suspected
shown to generate cell lineages different
from the organ they reside in
Stem cell therapy
New myocardium
adult hematopoietic stem cells show
potential to regenerate myocardium —
both myocytes and coronary vessels
injection of this cell in the region bordering
infarct in mice improved ventricle function
embryonic stem cells shown in vitro to
differentiate into cardiomyocytes
Orlic D, et al. Nature 2001;410(6829):701-705
Kocher AA, et al. Nat Med 2001;7(4):430-436
Stem cell therapy
Promising signs
“It is very clear that at this early stage there
are some promising signs that some of the
adult stem cells may in fact be able to turn
into other cells with appropriate stimulation.
Whether these cells will really become true
functioning liver or brain cells on their own
when they are put into a human being
remains to be determined.”
Robert Roberts MD
Chief of Cardiology
Baylor College of Medicine
Houston, Texas
Stem cell therapy
Summary
Embryonic stem cells
can form any 1 of the 200 different cell
types
obtained from 2 sources
 miscarried/aborted fetus
 unused fetus from in vitro fertilization
Adult stem cells
have a potential and have been successfully
used in the treatment of leukemia
Stem cell therapy
Cloning by nuclear transfer
different from stem cell
research
prohibited in the US but
approved in the UK
nucleus is taken out of one cell
and transplanted into another
recipient cell then adopts the
identity of the donor
Dolly, cloned by
nuclear transfer
(©Roslin Institute)
Stem cell therapy
Applications of stem cells
“This is very early in the game, and if we had
as many embryonic stem cells as we wanted
tomorrow, there is a lot of research to be done
in terms of what are the appropriate stimuli,
what could turn these cells into liver or heart
cells. Discovering what the particular stimuli
are may take 2 or 3 years, even if stem cell
research is approved and stem cells become
available from embryonic form.”
Robert Roberts MD
Chief of Cardiology
Baylor College of Medicine
Houston, Texas
Stem cell therapy
Cardiomyocytes
embryonic stem cells could be used to grow
cardiomyocites in vitro to be transplanted into MI
patients
adult stem cells
 could generate cardiomyocytes in culture, or
 could be injected directly into the MI animal
cells home to area of damage and generate new
myocardium, including electrically coupled myocytes
and coronary arterials and vessels
place
picture
here
Piero Anversa MD
Director, Cardiovascular
Research Institute
New York Medical College
Valhalla, New York
Stem cell therapy
A potential
“I think that there is a potential in the
adult stem cell…. Bone marrow-derived
stem cells have the capacity to go to areas
of damage in the myocardium and
generate new myocardium, composed of
myocytes and vessels.”
place
picture
here
Piero Anversa MD
Director, Cardiovascular
Research Institute
New York Medical College
Valhalla, New York
Stem cell therapy
In vitro
embryonic stem cells
used as in vitro model
 to study cardiac growth
 to investigate adverse
effects of drugs on
cardiac development
Stem cell therapy
Ethical debate
“I think that it is actually good to have this
controversy…this is a central issue that we
cannot avoid.”
Seigo Izumo MD
Professor of Medicine
Harvard Medical School
Boston, Massachusetts
“It was always intended by the NIH that, if this
research is going to be funded, a set of rules
has to be established for investigators to
follow.”
Robert Roberts MD
Chief of Cardiology
Baylor College of Medicine
Houston, Texas
Stem cell therapy
Adult stem cell research
“There will be little ethical issue for the use of
adult stem cells, in my opinion, particularly
concerning those coming from bone marrow.”
Seigo Izumo MD
Professor of Medicine
Harvard Medical School
Boston, Massachusetts
“The question is, can we get what we want by
just funding research in the adult stem cell?”
Robert Roberts MD
Chief of Cardiology
Baylor College of Medicine
Houston, Texas
Stem cell therapy
Location
how many adult stem cells lie in what organ is
still unclear
how to locate adult stem cells in the heart is
still unknown
more needs to be known about the
characteristics of the cell surface
answers may lie in the study of embryonic
stem cells
Robert Roberts MD
Chief of Cardiology
Baylor College of Medicine
Houston, Texas
Stem cell therapy
Complex issue
“We haven’t done any type of research to identify
whether there are stem cells in the heart like
there have found in the brain. I think the issue is
more complex than just analyzing, identifying,
characterizing, and understanding the biology of
embryonic stem cells. We need to also look for
stem cells in other organs which we always
thought were not present. We might be surprised
again, like we were a couple of years ago when
we found out that neural stem cells do exist.”
place
picture
here
Piero Anversa MD
Director, Cardiovascular
Research Institute
New York Medical College
Valhalla, New York
Stem cell therapy
Search for stem cells
how to search for the adult stem cell
 begin with markers used to isolate
hematopoietic primitive bone marrow cells
(c-kit, sca-1, mdr-1 etc)
several approaches can be used initially to see
whether there is a population of primitive
undifferentiated cells in the heart or the kidney, to
see whether there is a potential for regeneration in
these organs, and to try to interfere with disease
processes
place
picture
here
Piero Anversa MD
Director, Cardiovascular
Research Institute
New York Medical College
Valhalla, New York
Stem cell therapy
The heart
until recently, the heart
was assumed to be
terminally differentiated
 no previous search
for stem cells
“Certainly that’s a line of research that
should be pursued, and it is already
showing some promising results.”
Robert Roberts MD
Chief of Cardiology
Baylor College of Medicine
Houston, Texas
Stem cell therapy
The future
study of stem cells in mice and other species
may help identify human adult stem cells
taking advantage of evolutionary conservation
in development, one can probably identify a
number of markers for adult stem cells
“The availability of human stem cells will
probably hasten the research.”
Seigo Izumo MD
Professor of Medicine
Harvard Medical School
Boston, Massachusetts
Stem cell therapy
Conclusions
many fundamental uses for stem cells
great potential for both embryonic and adult
stem cell fields
every effort should be made to pursue adult
stem cells, regardless of what the future holds
for embryonic stem cell research
research with embryonic stem cells needs to
be properly debated and formulated
Robert Roberts MD
Chief of Cardiology
Baylor College of Medicine
Houston, Texas